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COVID-19 (Novel Coronavirus)

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General Information

Description

  • global pandemic of acute respiratory disease caused by a novel coronavirus (SARS-CoV-2)1
  • PubMed32123347Nature microbiologyNat Microbiol20200302SARS-CoV-2 is a member of beta genus coronaviruses closely related to SARS-CoV (Nat Microbiol 2020 Mar 2 early online)
  • common signs of COVID-19 include fever, cough, and shortness of breath1
  • there is no specific antiviral treatment for COVID-19, but supportive care may help to relieve symptoms and should include support of vital organ functions in severe cases1

Also Called

  • coronavirus disease 2019
  • SARS-CoV-2
  • 2019-nCoV

Definitions

  • World Health Organization (WHO) case definitions for surveillance
    • based on current information available and may be revised as new information accumulates
    • suspect case - any of
      • patient with severe acute respiratory infection (fever plus ≥ 1 sign or symptom of respiratory disease) requiring admission to hospital without another etiology that fully explains clinical presentation
      • patient with acute respiratory illness (fever plus ≥ 1 sign or symptom of respiratory disease) without another etiology that fully explains clinical presentation with history of travel to or residence in a country, area, or territory reporting local transmission within 14 days of symptom onset
      • patient with any acute respiratory illness with contact with a confirmed or probable case of COVID-19 within 14 days of symptom onset
    • probable case - suspect case with inconclusive test result for COVID-19
    • confirmed case - laboratory confirmed infection of COVID-19 regardless of clinical signs and symptoms
    • Reference - WHO Global Surveillance for human infection with coronavirus disease (COVID-19) 2020 Feb 27
  • Centers for Disease Control and Prevention (CDC) clinical criteria for patients under investigation (PUI)
    • clinicians should use their judgement to determine if a patient should be tested for COVID-19 based on local epidemiology and clinical course
      • most patients experience fever and symptoms of acute respiratory illness
      • clinicians are strongly encouraged to test for other respiratory illnesses including influenza
    • priorities for testing
      • in order to ensure optimal care for hospitalized patients, lessen nosocomial infection risk, and maintain healthcare system integrity, first priority for testing includes
        • hospitalized patients
        • symptomatic healthcare workers
      • in order to ensure persons at highest risk of complications are identified and triaged, second priority for testing includes the following
        • patients in long-term care facilities with symptoms
        • patients ≥ 65 years old with symptoms
        • patients with underlying conditions with symptoms
        • first responders with symptoms
      • as resources allow, test individuals in communities with rapidly increasing hospital cases in order to limit community spread and ensure health of essential workers, including
        • critical infrastructure workers with symptoms
        • individuals with symptoms not meeting the criteria above
        • healthcare workers and first responders
        • individuals with mild symptoms in communities experiencing high COVID-19 hospitalizations
    • Reference - CDC Interim Guidance for Healthcare Professionals 2020 Mar 24

Epidemiology

Geographic distribution

  • worldwide, although rate of infection varies by location and pandemic stage1

Who is most affected

  • Study Summary
    majority of cases of COVID-19 occur in adults
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 44,672 patients with confirmed COVID-19 with symptom onset between December 8, 2019 and February 11, 2020, in China's Infectious Disease Information System were evaluated
    • 86.6% of patients aged 30-79 years
    • percentage of cases by age
      • 0.9% in patients aged 0-9 years
      • 1.2% in patients aged 10-19 years
      • 8.1% in patients aged 20-29 years
      • 17% in patients aged 30-39 years
      • 19.2% in patients aged 40-49 years
      • 22.4% in patients aged 50-59 years
      • 19.2% in patients aged 60-69 years
      • 8.8% in patients aged 70-79 years
      • 3.2% in patients aged ≥ 80 years
    • Reference - Zhonghua Liu Xing Bing Xue Za Zhi 2020 Feb 17;41(2):145 [Chinese], also published in China CDC Weekly 2020;2(8):113 [English]
  • 167 confirmed cases of COVID-19 linked to skilled nursing facility in Washington, United States after contact tracing from first identified case (N Engl J Med 2020 Mar 27 early online)

Incidence/Prevalence

  • outbreak started in December 2019 in Wuhan, Hubei Province, China and declared a global pandemic on March 11, 2020 (WHO Situation Report 2020 Mar 11 PDF)
  • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorders2,878,196 confirmed cases of coronavirus disease 2019 (COVID-19) including 198,668 deaths worldwide reported by World Health Organization (WHO) as of April 27, 2020 (WHO Situation Report 2020 Apr 27)04/27/2020 10:03:40 PM2,878,196 confirmed cases of coronavirus disease 2019 (COVID-19) including 198,668 deaths worldwide reported by World Health Organization (WHO) as of April 27, 2020
    • European Region
      • 1,359,380 cases including 124,525 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed cases*New Confirmed cases*Total Deaths
        Spain207,634023,190
        Italy197,675 2,32426,644
        Germany155,1931,018 5,750
        United Kingdom152,844 4,46320,732
        France123,27940422,821
        Turkey110,1302,3572,805
        Russian Federation87,14712,559794
        Belgium46,1348097,094
        Netherlands37,8456554,475
        Switzerland28,97801,336
        Portugal23,864472903
        Ireland19,2627011,087
        Sweden18,6404632,194
        Israel15,3980199
        Austria15,18955542
        Poland11,617344535
        Romania11,036401608
        Belarus10,46387372
        Ukraine9,009392220
        Denmark8,575130422
        Serbia8,042263156
        Norway7,50538193
        Czechia7,40452221
        Finland4,576101190
        Luxembourg3,7231288
        Republic of Moldova3,40810496
        Kazakhstan2,79119025
        Hungary2,58383280
        Greece2,5060130
        Croatia2,0301455
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Region of the Americas
      • 1,140,520 cases including 58,492 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        United States931,69832,41747,980
        Brazil58,5095,5144,016
        Canada45,7781,4252,489
        Peru25,331 3,683700
        Ecuador22,7190576
        Mexico13,8429701,305
        Chile13,331473189
        Dominican Republic6,135209278
        Panama5,538200159
        Colombia5,142261233
        Argentina3,,838137179
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Eastern Mediterranean Region
      • 165,933 cases including 6,991 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        Iran90,4811,1535,710
        Saudi Arabia17,522 1,223139
        Pakistan13,328605281
        United Arab Emirates10,34953676
        Qatar10,28792910
        Egypt4,534215317
        Morocco4,065168161
        Kuwait3,07518320
        Bahrain2,647588
        Oman2,0495110
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Western Pacific Region
      • 144,121 cases including 5,958 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        China84,34134,643
        Singapore13,624 93112
        Japan13,385203351
        Republic of Korea10,73810243
        Philippines7,579285501
        Australia6,7131083
        Malaysia5,7803898
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • South-East Asia Region
      • 46,060 cases including 1,824 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        India27,8921,396872
        Indonesia8,882275743
        Bangladesh5,416418145
        Thailand2,931952
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • African Region
      • 21,470 cases including 865 deaths
      • countries most affected
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        South Africa4,54618587
        Algeria3,382126425
        Cameroon1,62110356
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Reference - WHO Situation Report 2020 Apr 27 PDF
  • United States
  • other resources for real-time case counts, maps, and graphs
  • Study Summary
    0.8% of general population in Iceland SARS-CoV-2 positive between March 13 and April 4, 2020
    Details
    Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disorders0.8% of general population in Iceland SARS-CoV-2 positive between March 13 and April 4, 2020 (N Engl J Med 2020 Apr 14 early online)04/17/2020 04:31:15 PMstudySummary
    • Cohort Study based on cohort study
    • 22,279 persons in Iceland had nasopharyngeal and oropharyngeal samples tested for SARS-CoV-2
      • 9,199 persons with symptoms, recent travel to high-risk countries, or contact with patients with known COVID-19 were targeted for testing between January 31 and March 31, 2020
      • 10,797 persons accepted open invitation to test between March 13 and April 1, 2020
      • 2,283 persons accepted random telephone text-based invitation to test between April 1 and April 4, 2020
    • positive SARS-CoV-2 test in
      • 13.3% of targeted individuals
      • 0.8% of screened individuals
        • 0.8% (95% CI 0.6%-1%) of those accepting open invitation
        • 0.6% (95% CI 0.3%-0.9%) of those invited at random
    • PubMed32289214The New England journal of medicineN Engl J Med20200414Reference - N Engl J Med 2020 Apr 14 early online

Risk factors

  • contact with persons with known, possible, or suspected COVID-19; persons at risk include
    • household members
    • intimate partners
    • individuals providing care in household without using recommended infection control precautions
    • individuals within 6 feet for prolonged period of time (greater than a few minutes)
    • Reference - CDC public health recommendations for people in United States communities exposed to a person with known or suspected COVID-19, other than healthcare workers or other critical infrastructure workers (CDC 2020 Mar 30)
  • travel to or residence in areas with ongoing community transmission (CDC public health recommendations after travel-associated COVID-19 exposure [CDC 2020 Mar 30])

Etiology and Pathogenesis

Pathogen

  • novel coronavirus clusters with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
    • genus Betacoronavirus
    • no consensus on exact taxonomic position within subgenus Sarbecovirus
    • species severe acute respiratory syndrome-related coronavirus
    • designated name SARS-CoV-2
    • PubMed32123347Nature microbiologyNat Microbiol20200302Reference - Nat Microbiol 2020 Mar 2 early online

Transmission

  • first cases associated with live animal market in Wuhan, China suggest initial animal-to-human spillover1
  • SARS-CoV-2 is transmitted person-to-person1
    • between close contacts (within 6 feet) via respiratory droplets produced when an infected person coughs or sneezes
    • contact with fomites may be possible, but it is not thought to be the primary route of transmission
    • PubMed32182409The New England journal of medicineN Engl J Med20200317viability of SARS-CoV-2 suggests aerosol and fomite transmission possible
      • median estimated half-life of SARS-CoV-2
        • 6.8 hours on plastic
        • 5.6 hours on stainless steel
        • 3.5 hours on cardboard
        • 1.1 hours in aerosol
        • 0.8 hours on copper
      • stability of SARS-CoV-2 similar to that of SARS-CoV-1
      • Reference - N Engl J Med 2020 Mar 17 early online
  • SARS-CoV-2 may be spread by people who are not showing symptoms1
  • Study Summary
    COVID-19 reported to have mean incubation period of 5.2 days with each case estimated to transmit infection to mean 2.2 other people in Wuhan, China
    Details
    Family_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disorders2019-nCoV reported to have mean incubation period of 5.2 days with each case estimated to transmit infection to mean 2.2 other people in Wuhan, China (N Engl J Med 2020 Jan 29 early online)02/11/2020 03:13:49 PMstudySummary
    • Cohort Study based on noncomparative data from cohort study
    • 425 adolescents and adults aged 15-89 years (median age 59 years, 38% ≥ 65 years old, 56% men) with first confirmed COVID-19 pneumonia in Wuhan, China, were assessed
      • 47 patients had illness onset before closure (January 1) of Huanan Seafood Wholesale Market (64% had exposure to wet market [Huanan Seafood Wholesale Market or other])
      • 248 patients had illness onset between closure of Huanan Seafood Wholesale Market and January 11, 2020, when real time-polymerase chain reaction reagents for identification were provided to Wuhan (16% had exposure to wet market)
      • 130 patients had illness onset during January 12-22, 2020 (6% had exposure to wet market)
    • incubation period assessed in 10 patients
      • mean incubation period 5.2 days (95% CI 4.1-7 days)
      • 95th percentile of distribution of incubation period 12.5 days (95% CI 9.2-18 days)
      • mean time between successive cases (mean serial interval) 7.5 days (95% CI 5.3-19 days)
    • mean duration from illness onset to first medical visit
      • 5.8 days (95% CI 4.3-7.5 days) in 45 patients with onset before January 1, 2020
      • 4.6 days (95% CI 4.1-5.1 days) in 207 patients with onset between January 1 and 11, 2020
    • assessment of epidemic curve up to January 4, 2020
      • on average, each patient spreads infection to 2.2 other people (basic reproductive number)
      • mean epidemic growth rate 0.1 per day (95% CI 0.05-0.16 per day)
      • mean doubling time 7.4 days (95% CI 4.2-14 days)
    • PubMed31995857The New England journal of medicineN Engl J Med20200129Reference - N Engl J Med 2020 Jan 29 early online
  • Study Summary
    doubling time of 6.4 days estimated based on COVID-19 infections exported from Wuhan, China, as of January 25, 2020
    Details
    Infectious_Diseases Internal_Medicinedoubling time of 6.4 days estimated based on COVID-19 infections exported from Wuhan, China, as of January 25, 2020 (Lancet 2020 Jan 31 early online)02/24/2020 02:43:24 PMstudySummary
    • Modeling study based on modeling study
    • statistical model used number of COVID-19 infections exported from Wuhan, China, to cities outside mainland China from December 1, 2019 to January 25, 2020
    • estimated COVID-19 basic reproductive number (R0) 2.68 (95% CrI 2.47-2.86)
    • estimated epidemic doubling time 6.4 days (95% CrI 5.8-7.1)
    • assuming no reduction in transmissibility, Wuhan epidemic estimated to peak around April 2020, with local epidemics across cities in mainland China estimated to lag by 1-2 weeks
    • assuming decreased transmissibility by 1-(1/R0) ≥ 63%, epidemics estimated to fade out
    • PubMed32014114Lancet (London, England)Lancet20200131Reference - Lancet 2020 Feb 29;395(10225):689, correction can be found in Lancet 2020 Feb 29;395(10225):e41
  • Study Summary
    SARS-CoV-2 viral shedding estimated to peak before or at onset of symptoms in patients with COVID-19
    Details
    Family_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_DisordersSARS-CoV-2 viral shedding estimated to peak before or at onset of symptoms in patients with COVID-19 (Nat Med 2020 Apr 15 early online)04/22/2020 10:36:46 AMstudySummary
    • Cohort Study based on retrospective cohort study and modeling study
    • in cohort study
      • 94 adults with laboratory-confirmed COVID-19 had viral loads assessed using polymerase chain reaction (PCR) of throat swabs from time of symptom onset up to 32 days after symptom onset
      • 66% were moderately ill (presenting with fever and/or respiratory symptoms and radiographic evidence of pneumonia) and none were classified as severely or critically ill on hospital admission
      • viral loads were highest at symptom onset and decreased gradually until below detection limit on about day 21
    • in modeling study
      • 77 transmission pairs within and outside mainland China were evaluated
        • estimated mean serial interval (time between onset of symptoms in successive cases in transmission chain) 5.8 days (95% CI 4.8-6.8 days)
        • mean incubation period (time between infection and symptom onset) assumed to be 5.2 days based on previous study
        • infectiousness inferred to begin 2.3 days before symptom onset (95% CI 0.8-3 days) with peak infectiousness at 0.7 days before symptom onset (95% CI -0.2 to 2 days)
      • estimated proportion of presymptomatic transmission 44% (95% CI 25%-69%)
    • PubMed32296168Nature medicineNat Med20200415Reference - Nat Med 2020 Apr 15 early onlinefull-text
  • Study Summary
    on African continent, Egypt, Algeria, and South Africa estimated to have highest import risk of COVID-19 from China and moderate-to-high vulnerability to epidemic emergency
    Details
    studySummary
    • Modeling study based on modeling study
    • model used
      • volume of air traffic arriving in Africa from provinces in China with infections to estimate risk of importation of infections
      • State Party Self-Assessment Annual Reporting to estimate capacity to respond to importation and spread of COVID-19 and Infectious Disease Vulnerability Index to estimate vulnerability to epidemic emergency based on demographic, environmental, socioeconomic, and political conditions in countries in Africa
    • Egypt, Algeria, and South Africa estimated to have highest import risk from China, with moderate-to-high capacity to respond and moderate-to-high vulnerability
    • Nigeria and Ethiopia estimated to have second highest importation risk, with moderate capacity to respond but high vulnerability with larger potential population exposure
    • Morocco, Sudan, Angola, Tanzania, Ghana, and Kenya have moderate importation risk, but with variable capacity to respond and high vulnerability (except for Morocco, which had moderate vulnerability)
    • PubMed32087820Lancet (London, England)Lancet20200220Reference - Lancet 2020 Mar 14;395(10227):871
  • Study Summary
    no intrauterine infection by vertical transmission reported in women with COVID-19 in late pregnancy
    Details
    Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Obstetric_and_Gynecologic_Conditions Primary_Careno intrauterine infection by vertical transmission reported in women with COVID-19 in late pregnancy (Lancet 2020 Mar 7)03/20/2020 11:38:54 AMstudySummary
    • Case Report based on review of case reports
    • 9 pregnant women in China with laboratory-confirmed COVID-19 pneumonia during third trimester were evaluated
    • common symptoms were fever (7 women), cough (4 women), myalgia (3 women), sore throat (2 women), and malaise (2 women)
    • all neonates delivered by cesarean section with 100% live birth
      • 0% neonatal asphyxia
      • 5-minute Apgar score 9-10 in all neonates
    • amniotic fluid, cord blood, neonatal throat swab samples, and breast milk samples from 6 mothers and infants were tested for SARS-CoV-2 to determine intrauterine vertical transmission
    • 100% of samples tested were negative for SARS-CoV-2
    • PubMed32151335Lancet (London, England)Lancet2020030739510226809-815809Reference - Lancet 2020 Mar 7;395(10226):809

Pathogenesis

  • pathogenesis of COVID-19 largely unknown, but early studies suggest
    • angiotensin-converting enzyme–related carboxypeptidase (ACE2) receptor used to gain entry to cells
      • ACE2 expressed in cardiopulmonary tissues
      • also expressed in hematopoietic cells such as monocytes and macrophages
    • lymphopenia associated with severe disease
    • T cell apoptosis and exhaustion may contribute to immunopathology
    • cytokine storm may play a role in severe COVID-19
      • cytokine release syndrome contributes to pathology of MERS-CoV and SARS-CoV-1 infections
      • elevated interleukin-6 (IL-6) is associated with ARDS and respiratory failure in patients with COVID-19
    • PubMed32303591Science (New York, N.Y.)Science20200417Reference - Science 2020 Apr 17 early online

History and Physical

History and Physical

Clinical Presentation

  • mild-moderate symptoms may arise 2-14 days after exposure1
    • most common symptoms include
      • cough
      • shortness of breath
      • difficulty breathing
    • other symptoms often include ≥ 2 of
      • fever
      • chills
      • repeated shaking with chills
      • muscle pain
      • headache
      • sore throat
      • new loss of smell or taste
  • COVID-19 may range from mild disease to severe illness1
    • Study Summary
      about 80% of cases of COVID-19 may be mild
      Details
      studySummary
      • Cohort Study based on retrospective cohort study
      • 44,672 patients with confirmed COVID-19 with symptom onset between December 8, 2019 and February 11, 2020, in China's Infectious Disease Information System were evaluated
      • among 44,415 patients with sufficient data, severity of disease was
        • mild (non-pneumonia and mild pneumonia) in 80.9%
        • severe (dyspnea, respiratory rate ≥ 30/minute, blood oxygen saturation ≤ 93%, PaO2/FiO2 ratio < 300, and/or lung infiltrates > 50% within 48 hours) in 13.8%
        • critical (respiratory failure, septic shock, and/or multiple organ dysfunction/failure) in 4.7%
      • PubMed32064853Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhiZhonghua Liu Xing Bing Xue Za Zhi20200217412145-151145Reference - Zhonghua Liu Xing Bing Xue Za Zhi 2020 Feb 17;41(2):145 [Chinese], also published in China CDC Weekly 2020;2(8):113 [English]
    • Study Summary
      mild or moderate respiratory disease reported in almost 90% of children with confirmed or suspected COVID-19
      Details
      Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Pediatrics Primary_Care Pulmonary_Disordersmild or moderate respiratory disease reported in almost 90% of children with confirmed or suspected COVID-19 (Pediatrics 2020 Mar 16 early online)03/30/2020 09:08:49 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 2,143 children (median age 7 years) with COVID-19 reported to Chinese Center for Disease Control and Prevention between January 16 and February 8, 2020 were evaluated
      • 34.1% had laboratory-confirmed COVID-19 and 65.9% had suspected disease
      • severity of disease
        • asymptomatic in 4.4%
        • mild (non-pneumonia upper respiratory infection) in 50.9%
        • moderate (pneumonia without obvious hypoxia) in 38.8%
        • severe (pneumonia with hypoxia) in 5.2%
        • critical (acute respiratory distress syndrome, respiratory failure, shock, encephalopathy, myocardial injury or heart failure, coagulation dysfunction, or acute kidney injury) in 0.6%
      • among 13 critical patients, 7 (53.8%) were aged < 1 year
      • PubMed32179660PediatricsPediatrics20200316Reference - Pediatrics 2020 Mar 16 early online
  • Study Summary
    fever, cough, and fatigue most common clinical features in patients with COVID-19 in China
    Details
    Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disordersfever, cough, and fatigue most common clinical features in patients with COVID-19 (J Med Virol 2020 Apr 15 early online)04/22/2020 11:46:49 AMstudySummary
    • Systematic Review based on systematic review of observational studies
    • systematic review of 38 observational studies evaluating clinical characteristics of 3,062 patients with COVID-19 in China between January 1 and February 28, 2020
    • male sex in 56.9% (95% CI 55%-58.4%) in analysis of all patients
    • symptoms included
      • fever in 80.4% (95% CI 73%-86.9%) in analysis of 35 studies with 2,966 patients
      • cough in 63.1% (95% CI 57.9%-68.2%) in analysis of 36 studies with 2,979 patients
      • fatigue in 46% (95% CI 38.2%-54%) in analysis of 26 studies with 2,595 patients
      • expectoration in 41.8% (95% CI 33.9%-50%) in analysis of 17 studies with 1,908 patients
      • anorexia in 38.8% (95% CI 14.1%-67.1%) in analysis of 6 studies with 467 patients
      • chest tightness in 35.7% (95% CI 23.2%-49.3%) in analysis of 14 studies with 660 patients
      • shortness of breath in 35% (95% CI 21.7%-49.8%) in analysis of 8 studies with 1,379 patients
      • dyspnea in 33.9% (95% CI 24.2%-44.3%) in analysis of 14 studies with 955 patients
      • muscle soreness in 33% (95% CI 26%-40.5%) in analysis of 25 studies with 2,444 patients
      • chest pain in 28.3% (95% CI 1%-72.9%) in analysis of 2 studies with 87 patients
      • headache in 15.4% (95% CI 11.6%-19.6%) in analysis of 24 studies with 2,452 patients
      • pharyngalgia in 13.1% (95% CI 7.4%-20.3%) in analysis of 10 studies with 751 patients
      • diarrhea in 12.9% (95% CI 9%-17.4%) in analysis of 24 studies with 2,378 patients
      • shivering in 11% (95% CI 5.8%-17.4%) in analysis of 5 studies with 314 patients
      • nausea and vomiting in 10.2% (95% CI 5.4%-16.3%) in analysis of 10 studies with 1,638 patients
      • abdominal pain in 4.4% (95% CI 2.5%-6.9%) in analysis of 5 studies with 545 patients
    • asymptomatic presentation in 11.9% (95% CI 2.9%-25.8%) in analysis of 5 studies with 158 patients
    • imaging findings
      • bilateral lung involvement in 75.7% (95% CI 65.7%-84.5%) in analysis of 22 studies with 2,185 patients
      • single lung involvement in 25.8% (95% CI 15.6%-37.4%) in analysis of 12 studies with 600 patients
    • laboratory findings included
      • lymphopenia in 56.5% (95% CI 46.5%-66.4%) in analysis of 24 studies with 2,507 patients
      • leukopenia in 25.9% (95% CI 19.6%-32.7%) in analysis of 22 studies with 2,258 patients
      • leukocytosis in 12.6% (95% CI 8.4%-17.4%) in analysis of 15 studies with 1,992 patients
      • elevated C-reactive protein in 73.6% (95% CI 66.1%-80.4%) in analysis of 21 studies with 2,238 patients
      • elevated erythrocyte sedimentation rate in 65.6% (95% CI 36.8%-89.3%) in analysis of 3 studies with 195 patients
      • decreased oxygenation index in 63.6% (95% CI 32.4%-89.5%) in analysis of 4 studies with 113 patients
      • elevated D-dimer in 37.2% (95% CI 17.7%-59.1%) in analysis of 6 studies with 414 patients
      • abnormal liver function in 29% (95% CI 17.5%-42.1%) in analysis of 10 studies with 549 patients
      • abnormal renal function in 25.5% (95% CI 5.6%-53.5%) in analysis of 5 studies with 231 patients
      • elevated procalcitonin in 17.5% (95% CI 7.8%-29.9%) in analysis of 9 studies with 1,701 patients
    • respiratory failure or acute respiratory distress syndrome (ARDS) in 19.5% (95% CI 5%-40.3%) in analysis of 8 studies with 1,499 patients
    • mortality 5.5% (95% CI 2.3%-10%) in analysis of 8 studies with 1,765 patients
    • PubMed32293716Journal of medical virologyJ Med Virol20200415Reference - J Med Virol 2020 Apr 15 early online
    • Critical_Care Infectious_Diseases Internal_Medicine Pulmonary_Disordersfever, fatigue, and cough most common clinical features in adults with 2019-nCoV pneumonia (JAMA 2020 Feb 7 early online)02/13/2020 12:35:56 PMfever, fatigue, and cough most common clinical features in adults with COVID-19 pneumonia in China
      • based on 3 cohort studies
      • cohort admitted to Zhongnan Hospital in Wuhan, China, January 1-28, 2020
        • 138 adults aged 22-92 years (median age 56 years, 54% men) with confirmed COVID-19 pneumonia consecutively admitted to Zhongnan Hospital in Wuhan, China, January 1-28, 2020, were evaluated through February 3, 2020
          • 29% were medical staff, 12.3% were already hospitalized patients, and 8.7% had exposure to Huanan seafood market
          • 46.4% had ≥ 1 comorbidity, most commonly hypertension (31.2%), cardiovascular disease (14.5%), diabetes (10.1%), malignancy (7.2%), and cerebrovascular disease (5.1%)
        • median duration from first symptoms to
          • dyspnea 5 days
          • hospital admission 7 days
          • ARDS 8 days
        • clinical features included
          • fever in 98.6%
          • fatigue in 69.6%
          • dry cough in 59.4%
          • anorexia in 39.9%
          • myalgia in 34.8%
          • dyspnea in 31.2%
          • expectoration in 26.8%
          • pharyngalgia in 17.4%
          • diarrhea in 10.1%
          • nausea in 10.1%
          • dizziness in 9.4%
          • headache in 6.5%
          • vomiting in 3.6%
          • abdominal pain in 2.2%
        • 100% had bilateral patchy shadows or ground-glass opacity in lungs on chest computed tomography
        • laboratory testing revealed
          • lymphopenia (lymphocyte count < 1.1 × 109 cells/L) in 70.3%
          • prolonged prothrombin time (> 12.5 seconds) in 58%
          • elevated lactate dehydrogenase (> 243 units/L) in 39.9%
        • severity of illness median scores in 36 patients in intensive care unit
          • Acute Physiology and Chronic Health Evaluation II 12 points
          • Sequential Organ Failure Assessment 5 points
          • Glasgow Coma Scale 15 points
        • complications included
          • ARDS in 19.6%
          • arrhythmia in 16.7%
          • shock in 8.7%
          • acute cardiac injury in 7.2%
          • acute kidney injury in 3.6%
        • 12.3% required invasive ventilation (4 switched to extracorporeal membrane oxygenation)
        • 1.4% required continuous renal replacement therapy
        • 34.1% discharged from hospital (median hospital stay 10 days)
        • 4.3% died
        • Reference - JAMA 2020 Feb 7 early online, commentary can be found in JAMA 2020 Feb 5 early online
      • cohort admitted to Jinyintan Hospital in Wuhan, China, by January 2, 2020
        • 41 patients (mean age 49 years, 73% male) with confirmed COVID-19 pneumonia admitted to Jinyintan Hospital in Wuhan, China, by January 2, 2020, were evaluatedCritical_Care Infectious_Diseases Internal_Medicine Pulmonary_Disordersfever and cough most common clinical features in patients with 2019-nCoV pneumonia (Lancet 2020 Jan 24 early online)01/28/2020 08:59:32 AM
          • 66% had exposure to Huanan seafood market
          • 32% had ≥ 1 comorbidity, most commonly diabetes (20%), hypertension (15%), and/or cardiovascular disease (15%)
          • median duration from first symptoms to hospital admission 7 days
        • clinical features included
          • fever in 98%
          • cough in 76%
          • dyspnea in 55%
          • myalgia or fatigue in 44%
          • sputum production in 28%
          • headache in 8%
          • hemoptysis in 5%
          • diarrhea in 3%
        • bilateral multiple lobular and subsegmental areas of consolidation were common findings on chest computed tomography
        • laboratory testing revealed
          • lymphopenia (lymphocyte count < 1 × 109 cells/L) in 63%
          • elevated aspartate aminotransferase levels in 37%
          • leukopenia (white blood cell count < 4 × 109 cells/L) in 25%
          • viremia in 15%
        • complications included
          • ARDS in 29%
          • acute cardiac injury in 12%
          • secondary infection in 10%
        • 10% required invasive mechanical ventilation
        • 15% died
        • Reference - Lancet 2020 Feb 15;395(10223):497full-text, correction can be found in Lancet 2020 Feb 15;395(10223):496
      • cohort admitted to Jinyintan Hospital in Wuhan, China, from January 1 to 20, 2020
        • 99 adults aged 21-82 years (mean age 55 years, 68% men) with confirmed COVID-19 pneumonia admitted to Jinyintan Hospital in Wuhan, China, from January 1 to 20, 2020, were evaluated up to January 25, 2020
          • 49% had exposure to Huanan seafood market
          • 51% had ≥ 1 comorbidity, most commonly cardiovascular and cerebrovascular disease (40%), digestive system disease (11%), and endocrine system disease (13%)
        • clinical features included
          • fever in 83%
          • cough in 82%
          • dyspnea in 31%
          • muscle ache in 11%
          • confusion in 9%
          • headache in 8%
          • sore throat in 5%
          • rhinorrhea in 4%
          • chest pain in 2%
          • diarrhea in 2%
          • nausea and vomiting in 1%
        • chest x-ray and computed tomography findings
          • bilateral pneumonia in 75%
          • multiple mottling and ground-glass opacity in 14%
          • pneumothorax in 1%
        • laboratory testing revealed
          • increased lactate dehydrogenase (> 250 units/L) in 76%
          • decreased hemoglobin (< 130 g/L) in 51%
          • neutrophilia (neutrophil count > 6.3 × 109 cells/L) in 38%
          • lymphopenia (lymphocyte count < 1.1 × 109 cells/L) in 35%
          • leukocytosis (white blood cell count > 9.5 × 109 cells/L) in 24%
          • thrombocytopenia (platelet count < 125 × 109 platelets/L) in 12%
          • leukopenia (white blood cell count < 3.5 × 109 cells/L) in 9%
          • thrombocytosis (platelet count > 350 × 109 platelets/L) in 4%
        • complications included
          • ARDS in 17%
          • ventilator-associated pneumonia in 11%
          • acute respiratory injury in 8%
          • septic shock in 4%
          • acute kidney injury in 3%
        • 4% required invasive mechanical ventilation
        • 3% required extracorporeal membrane oxygenation
        • 9% required continuous renal replacement therapy
        • 31% discharged from hospital
        • 11% died
        • Reference - Lancet 2020 Feb 15;395(10223):507full-text
  • Study Summary
    chest distress and shortness of breath more common in older patients with COVID-19
    Details
    Critical_Care Family_Medicine Geriatrics Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disorderschest distress and shortness of breath more common in older patients with COVID-19 (J Gerontol A Biol Sci Med Sci 2020 Apr 11 early online)04/27/2020 02:08:06 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 203 adults (median age 54 years) with COVID-19 admitted to 1 hospital in Wuhan, China from January 1, 2020 to February 10, 2020 were evaluated
    • 55 patients were ≥ 65 years old
    • comparing patients ≥ 65 years old vs. patients < 65 years old
      • comorbidities in 67.3% vs. 34.5% (p < 0.01)
      • median time from illness onset to hospital admission 7.1 days vs. 5.5 days (p = 0.05)
      • disease severity at admission
        • stable in 12.7% vs. 60.1% (p < 0.01)
        • serious in 43.6% vs. 33.1% (not significant)
        • critical in 43.6% vs. 6.8% (p < 0.01)
      • symptoms
        • chest distress in 63.6% vs. 25% (p < 0.01)
        • shortness of breath in 58.2% vs. 18.2% (p < 0.01)
        • anorexia in 9.1% vs. 0.7% (p = 0.01)
        • no significant differences in fever, dry cough, myalgia or arthralgia, fatigue, headache, diarrhea, abdominal pain, nausea, vomiting, chest pain, dizziness, or dyspnea
      • imaging findings
        • bilateral involvement in 98.2% vs. 79.7% (p < 0.01)
        • pleural effusion in 23.6% vs. 5.4% (p < 0.01)
        • 5-day disease progression in 36.4% vs. 18.9% (p = 0.01)
      • laboratory findings
        • lymphopenia (lymphocyte count < 1 × 109/L) in 81.8% vs. 48.6% (p < 0.01)
        • leukocytosis (white blood cell count > 10 × 109/L) in 18.2% vs. 2.7% (p < 0.01)
        • abnormal blood biochemistry results more common in patients ≥ 65 years old
      • median length of hospital stay 12 days vs. 10 days (not significant)
      • mortality 34.5% vs. 4.7% (p < 0.001)
    • PubMed32279081The journals of gerontology. Series A, Biological sciences and medical sciencesJ Gerontol A Biol Sci Med Sci20200411Reference - J Gerontol A Biol Sci Med Sci 2020 Apr 11 early online
  • Study Summary
    hypertension, obesity, and diabetes reported to be most common comorbidities in patients hospitalized with COVID-19 in New York, United States
    Details
    Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disordershypertension, obesity, and diabetes reported to be most common comorbidities in patients hospitalized with COVID-19 in New York, United States (JAMA 2020 Apr 22 early online)04/27/2020 02:37:49 PMstudySummary
    • Cohort Study based on cohort study with noncomparative data
    • 5,700 patients (median age 63 years, 60% men) with COVID-19 admitted to 12 hospitals in New York from March 1, 2020 to April 4, 2020 were assessed
    • comorbidities included
      • hypertension in 57%
      • obesity (body mass index ≥ 30 kg/m2) in 42%
      • diabetes in 34%
      • coronary artery disease in 11%
      • asthma in 9%
      • heart failure in 6.9%
      • cancer in 6%
      • chronic obstructive pulmonary disease in 5.4%
      • chronic kidney disease in 5%
    • at triage or admission
      • fever in 31%
      • oxygen saturation < 90% in 20%
      • respiratory rate > 24 breaths/minute in 17%
      • corrected QT interval > 500 milliseconds in 6.1%
      • respiratory viral panel positive for non-COVID-19 respiratory virus in 2.1%
    • supplemental oxygen given to 28% at triage
    • PubMed32320003JAMAJAMA20200422Reference - JAMA 2020 Apr 22 early online
  • Study Summary
    neurologic manifestations present in about one-third of patients with COVID-19
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Neurologic_Disordersneurologic manifestations present in about one-third of patients with COVID-19 (JAMA Neurol 2020 Apr 10 early online)04/15/2020 08:37:38 AMstudySummary
    • Cohort Study based on retrospective cohort study
    • 214 patients (mean age 52 years) with COVID-19 hospitalized in 3 special care centers in Wuhan, China, between January 16 and February 19, 2020 were evaluated
    • neurologic manifestations in 36.4%
      • central nervous system manifestations in 24.8%
        • dizziness in 16.8%
        • headache in 13.1%
        • impaired consciousness in 7.5%
        • acute cerebrovascular disease in 2.8%
        • ataxia in 0.5%
        • seizure in 0.5%
      • peripheral nervous system manifestations in 8.9%
        • taste impairment in 5.6%
        • smell impairment in 5.1%
        • nerve pain in 2.3%
        • vision impairment in 1.4%
      • skeletal muscle injury in 10.7%
    • nervous system manifestations in 45.5% of patients with severe disease vs. 30.2% of patients with nonsevere disease (p = 0.02)
    • PubMed32275288JAMA neurologyJAMA Neurol20200410Reference - JAMA Neurol 2020 Apr 10 early online
  • Study Summary
    olfactory and gustatory dysfunction reported in most adults with mild-to-moderate COVID-19 infection in Europe who were assessed for these symptoms
    Details
    Ear,_Nose,_and_Throat_Disorders_(Otorhinolaryngology) Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Neurologic_Disorders Primary_Careolfactory and gustatory dysfunction reported in most adults with mild-to-moderate COVID-19 infection in Europe who were assessed for these symptoms (Eur Arch Otorhinolaryngol 2020 Apr 6 early online)04/15/2020 08:38:49 AMstudySummary
    • Cohort Study based on retrospective cohort study
    • 417 adults (mean age 36 years, 63% women) with mild-to-moderate COVID-19 in Europe were assessed clinically and via National Health and Nutrition Examination Survey and short version of Questionnaire of Olfactory Disorders-Negative Statements
    • most common symptoms were cough (reported in 78% of patients), myalgia (in 58%), appetite loss (in 52%), diarrhea (in 51%), fever (in 48%), headache (in 45%), and asthenia (in 45%) (values estimated from figure)
    • olfactory dysfunction reported in 357 patients (85.6%), of whom
      • 79.6% had anosmia
      • 32.4% had parosmia
      • 20.4% had hyposmia
      • 12.6% had phantosmia
    • timing of olfactory dysfunction
      • onset occurred after onset of general or ear, nose, and throat symptoms in 65.4%, at same time in 22.8%, and after onset of other symptoms in 11.8%
      • persisted after resolution of other symptoms in 63% of 247 patients with clinically resolved infection
      • resolved within 8 days of clinical resolution of COVID-19 in 72.6% of 59 patients with clinical cure
    • olfactory dysfunction not associated with altered rates of rhinorrhea or nasal obstruction
    • gustatory dysfunction reported in 342 patients (82%), of whom
      • 78.9% had reduced taste
      • 21.1% had distorted taste
    • Reference - Eur Arch Otorhinolaryngol 2020 Apr 6 early online
  • Study Summary
    prevalence of gastrointestinal (GI) symptoms about 18% in patients with confirmed COVID-19
    Details
    Family_Medicine Gastrointestinal_Disorders Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Careprevalence of gastrointestinal symptoms about 18% in patients with confirmed COVID-19 (Gastroenterology 2020 Apr 3 early online)04/22/2020 11:48:19 AMstudySummary
    • Systematic Review based on systematic review of observational studies
    • systematic review of 69 observational studies with data on gastrointestinal symptoms and stool viral load in patients with COVID-19
      • 60 studies evaluated gastrointestinal symptoms in 4,243 children and adults (including pregnant women) with COVID-19 in 6 countries (88% of studies in China)
    • prevalence of gastrointestinal symptoms (including anorexia, nausea, vomiting, diarrhea, and abdominal pain)
      • 17.6% overall (95% CI 12.3%-24.5%) in analysis of 60 studies
        • 16.7% of patients (95% CI 11.4%-23.9%) in analysis of 53 studies in adults
        • 24.8% of patients (95% CI 9.6%-50.4%) in analysis of 4 studies in children
        • 20% of patients (95% CI 4.3%-58.2%) in analysis of 3 studies in pregnant women
    • 48.1% of patients (95% CI 38.3%-57.9%) had stool and respiratory samples positive for SARS-CoV-2 RNA in analysis of 13 studies with 138 patients
    • 70.3% of patients (95% CI 49.6%-85.1%) had positive stool test after negative respiratory test in analysis of 9 studies with 124 patients
    • in additional cohort of 59 patients with confirmed COVID-19 in Hong Kong during February 2-29, 2020
      • 25.4% had gastrointestinal symptoms (22% had diarrhea)
      • 15.3% had stool test positive SARS-CoV-2 RNA (38.5% in patients with diarrhea and 8.7% in patients without diarrhea)
    • PubMed32251668GastroenterologyGastroenterology20200403Reference - Gastroenterology 2020 Apr 3 early online
  • cutaneous manifestations
    • Study Summary
      cutaneous manifestations of erythematous rash, urticaria or vesicles reported in about 20% of patients hospitalized with COVID-19 in Italy
      Details
      Critical_Care Dermatologic_Disorders Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disorderscutaneous manifestations of erythematous rash, urticaria or vesicles reported in about 20% of patients hospitalized with COVID-19 in Italy (J Eur Acad Dermatol Venereol 2020 Mar 26 early online)04/24/2020 09:10:51 AMstudySummary
      • Cohort Study based on cohort study
      • 88 patients hospitalized with COVID-19 in the Lecco Hospital, Lombardy, Italy were evaluated for skin manifestations by dermatologists (patients with new drug exposure within 15 days prior to hospitalization were excluded)
      • 18 patients (20.4%) had cutaneous manifestations (8 patients had skin symptoms at onset of illness and 10 patients developed skin symptoms during hospitalization)
        • erythematous rash in 14 patients (16%)
        • widespread urticaria in 3 patients
        • chickenpox-like vesicles in 1 patients
      • most skin symptoms were found on the trunk and associated with minimal pruritus
      • PubMed32215952Journal of the European Academy of Dermatology and Venereology : JEADVJ Eur Acad Dermatol Venereol20200326Reference - J Eur Acad Dermatol Venereol 2020 Mar 26 early online
    • Study Summary
      varicella-like exanthem, characterized by papulovesicular lesions of the trunk, reported in patients with COVID-19
      Details
      Critical_Care Dermatologic_Disorders Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disordersvaricella-like exanthem, characterized by papulovesicular lesions of the trunk, reported in patients with COVID-19 (J Am Acad Dermatol 2020 Apr 16 early online)04/24/2020 09:13:12 AMstudySummary
      • Cohort Study based on cohort study
      • 22 patients with COVID-19 and a papulovesicular exanthem who were evaluated in Dermatology Units in Italy were reviewed
      • patients with history of any new medication in ≤ 15 days prior to rash were excluded
      • clinical characteristics of rash
        • lesion onset at mean 3 days after systemic symptoms (range of onset from 2 days prior to 12 after systemic symptoms)
        • scattered or diffuse papulovesicular lesions on the trunk in 22 patients (100%)
        • scattered or diffuse papulovesicular lesions on extremities in 4 patients (18%)
        • no facial or mucosal involvement
        • associated pruritus (generally mild) in 9 patients (41%)
        • median duration of rash of 8 days (range 4-15 days)
      • systemic symptoms included fever in 96%, cough in 73%, headache in 50%, weakness in 50%, coryza in 46%, dyspnea in 41%, hyposmia in 18%, hypogeusia in 18%, pharyngodynia in 5%, and diarrhea in 5%
      • mortality 14%
      • PubMed32305439Journal of the American Academy of DermatologyJ Am Acad Dermatol20200416Reference - J Am Acad Dermatol 2020 Apr 16 early onlinefull-text
    • PubMed32220276Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhiZhonghua Xue Ye Xue Za Zhi20200328410E006E006 acroischemia, characterized by cyanosis of the fingers and/or toe, skin bulla and dry gangrene reported in 7 patients hospitalized with critical COVID-19 in Wuhan, China from Feb 4 to Feb 15, 2020 (Zhonghua Xue Ye Xue Za Zhi 2020 Mar 28;41(0):E006)
  • pediatric patients
    • Study Summary
      wide spectrum of clinical features and disease severity in children with SARS-CoV-2 infection in China
      Details
      Critical_Care Family_Medicine Immunologic_Disorders Internal_Medicine Pediatrics Primary_Care Pulmonary_Disorderswide spectrum of clinical features and disease severity reported in children with SARS-CoV-2 infection in China (N Engl J Med 2020 Mar 18 early online)03/24/2020 07:02:35 PMstudySummary
      • Cohort StudySystematic Review based on retrospective cohort study and systematic review of observational studies
      • 171 children (median age 6 years, 61% male) with SARS-CoV-2 infection at Wuhan Children's Hospital between January 28, 2020 and February 26, 2020 were evaluated
        • spectrum of illness
          • pneumonia in 111 children (64.9%), of whom 12 had radiologic features of pneumonia without symptoms
          • upper respiratory tract infection in 33 children (19.3%)
          • asymptomatic infection without radiologic features of pneumonia in 27 children (15.8%)
        • clinical features included
          • cough in 48.5%
          • pharyngeal erythema in 46.2%
          • fever in 41.5%
          • tachycardia on admission in 42.1%
          • tachypnea on admission in 28.7%
          • diarrhea in 8.8%
          • fatigue in 7.6%
          • rhinorrhea in 7.6%
          • vomiting in 6.4%
          • nasal congestion in 5.3%
          • oxygen saturation < 92% during hospitalization in 2.3%
        • chest computed tomography findings included
          • ground-glass opacity in 32.7%
          • local patchy shadowing in 18.7%
          • bilateral patchy shadowing in 12.3%
          • interstitial abnormalities in 1.2%
        • blood testing identified lymphopenia < 1.2 × 109 cells/L in 3.5%
        • 3 children required intensive care support and invasive mechanical ventilation (all had coexisting conditions)
        • 1 child died (10-month-old child with intussusception died of multiorgan failure)
        • PubMed32187458The New England journal of medicineN Engl J Med20200318Reference - N Engl J Med 2020 Mar 18 early online
      • Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Pediatrics Primary_Carewide spectrum of clinical features and disease severity in children with SARS-CoV-2 infection in China (J Formos Med Assoc 2020 Apr 16 early online)04/27/2020 03:24:32 PMsystematic review of 9 observational studies evaluating pediatric patients with COVID-19 or born to mothers with COVID-19 in China between January 2020 and March 15, 2020
        • 7 studies evaluated 93 pediatric patients aged 1 day to 17 years with COVID-19 and 2 studies evaluated 19 neonates born to mothers with COVID-19
        • clinical characteristics in pooled analysis of 7 studies with 93 pediatric patients (52% male) with COVID-19
          • 98% had mild-to-moderate disease (severe or critical disease in 1% each)
          • common symptoms included
            • fever in 59%
            • cough in 46%
            • GI symptoms in 12%
          • asymptomatic at presentation in 26%
          • 2 children required intensive care including 1 with complications
        • chest computed tomography findings in pooled analysis of 3 studies with 52 pediatric patients
          • ground glass opacities in 48%
          • patchy consolidations in 31%
          • no lesions in 27%
        • lymphopenia in pooled analysis of 22 children with available laboratory data
          • lymphocyte count < 1,500 cells/mcL in 32%
          • lymphocyte count < 1,000 cells/mcL in 9%
        • pooled analysis of neonates born to mothers with COVID-19 in 2 studies with 19 neonates
          • age 31-39 weeks gestation
          • maternal fever in 83%
          • cesarean section in 89%
          • preterm birth in 53%
          • birth weight < 2,500 g in 47%
          • mean 1 minute Apgar score 9
          • mean 5 minute Apgar score 10
          • no neonates tested positive for SARS-CoV-2
          • no neonatal death reported
        • PubMed32307322Journal of the Formosan Medical Association = Taiwan yi zhiJ Formos Med Assoc20200416Reference - J Formos Med Assoc 2020 Apr 16 early onlinefull-text
    • Study Summary
      wide spectrum of clinical features reported in children and adolescents with confirmed SARS-CoV2 infection in United States
      Details
      Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Pediatrics Primary_Carewide spectrum of clinical features reported in children and adolescents with confirmed SARS-CoV2 infection in United States (MMWR Morb Mortal Wkly Rep 2020 Apr 10)04/13/2020 09:20:09 AMstudySummary
      • Cohort Study based on cohort study
      • 149,082 confirmed cases of SARS-CoV2 infection in United States between February 12 and April 2, 2020, were assessed
      • 2,572 cases were children and adolescents < 18 years old (median age 11 years, 57% males)
        • 32% were aged 15-17 years
        • 27% were aged 10-14 years
        • 15% were aged 5-9 years
        • 11% were aged 1-4 years
        • 15% were < 1 year old
      • prevalence of underlying condition in 345 children and adolescents with available data
        • overall 23%
        • chronic lung disease in 11.6%
        • cardiovascular disease in 7.2%
        • immunosuppression in 2.9%
      • clinical features in 291 children and adolescents with available data
        • ≥ 1 of fever, cough, or shortness of breath in 73%
        • fever in 56%
        • cough in 54%
        • headache in 28%
        • sore throat in 24%
        • myalgia in 23%
        • shortness of breath in 13%
        • diarrhea in 13%
        • nausea or vomiting in 11%
        • runny nose in 7.2%
        • abdominal pain in 5.8%
      • level of care in 745 children and adolescents with available data
        • hospitalization in 19.7% (estimated range 5.7%-20%)
        • admission to intensive care unit in 2% (estimated range 0.5%-2%)
      • level of care in 95 infants < 1 year old with available data
        • hospitalization in 62%
        • admission to intensive care unit in 5.3%
      • prevalence of underlying condition by level of care in 295 children and adolescents with available data
        • 77% for hospitalized patients
        • 12% for patients not hospitalized
      • 3 deaths reported (cause of death is pending)
      • PubMed32271728MMWR. Morbidity and mortality weekly reportMMWR Morb Mortal Wkly Rep202004106914422-426422Reference - MMWR Morb Mortal Wkly Rep 2020 Apr 10;69(14):422full-text

History

  • ask about recent travel to or residence in affected areas1
  • ask about exposure to patients with confirmed or suspected COVID-19, such as within household or healthcare facility1

Diagnosis

DiagnosisDiagnosis

Who to Test

  • World Health Organization (WHO) interim guidance for diagnosis and testing for COVID-19
    • suspect COVID-19 in patients with
      • severe acute respiratory infection (fever plus ≥ 1 symptom of respiratory disease and requiring admission to hospital) without another etiology that fully explains clinical presentation
      • acute respiratory illness (fever plus ≥ 1 symptom of respiratory disease) without another etiology that fully explains clinical presentation and history of travel or residence in a region with local transmission of COVID-19 within 14 days of symptom onset
      • any acute respiratory illness and contact with confirmed or probable case of COVID-19 within 14 days of symptom onset
    • Reference - WHO Global Surveillance for human infection with novel coronavirus (2019-nCoV) 2020 Feb 27
  • Centers for Disease Control and Prevention (CDC) interim guidance for evaluation of patients under investigation (PUI)
    • clinicians should use their judgement to determine if a patient should be tested for COVID-19 based on local epidemiology and clinical course
      • most patients experience fever and symptoms of acute respiratory illness
      • clinicians are strongly encouraged to test for other respiratory illnesses including influenza
    • priorities for testing
      • in order to ensure optimal care for hospitalized patients, lessen nosocomial infection risk, and maintain healthcare system integrity, first priority for testing includes
        • hospitalized patients
        • symptomatic healthcare workers
      • in order to ensure persons at highest risk of complications are identified and triaged, second priority for testing includes the following
        • patients in long-term care facilities with symptoms
        • patients ≥ 65 years old with symptoms
        • patients with underlying conditions with symptoms
        • first responders with symptoms
      • as resources allow, test individuals in communities with rapidly increasing hospital cases in order to limit community spread and ensure health of essential workers, including
        • critical infrastructure workers with symptoms
        • individuals with symptoms not meeting the criteria above
        • healthcare workers and first responders
        • individuals with mild symptoms in communities experiencing high COVID-19 hospitalizations
    • report PUI for COVID-19
      • immediately notify both infection control personnel at healthcare facility and local or state health department
      • state health departments that have identified a PUI should immediately
        • contact CDC’s Emergency Operations Center (EOC) at 770-488-7100 and
        • complete a COVID-19 PUI case investigation available by CDC
    • Reference - CDC Interim Guidance for Healthcare Professionals 2020 Mar 24

Sample Collection and Testing for SARS-CoV-2

  • WHO interim guidance on laboratory testing for COVID-19
    • sample collection and shipment
      • ensure adequate biosafety practices for collection and testing
      • at minimum, respiratory material should be collected
        • upper respiratory specimens include nasopharyngeal swab, wash, or aspirate, and oropharyngeal swab in ambulatory patients
        • lower respiratory specimens include sputum (if produced), endotracheal aspirate, or bronchoalveolar lavage in patients with more severe disease
      • additional specimens may include stool, whole blood, urine, or autopsy material if person is deceased
      • serum samples may be collected for use when serologic testing is validated and available
      • specimens should reach laboratory as soon as possible
      • communication with laboratory encourages proper and timely processing and reporting
    • testing for COVID-19
      • nucleic acid amplification test (NAAT) for SARS-CoV-2 currently test of choice
        • confirmation of COVID-19
          • in areas with established SARS-CoV-2 circulation, confirmation requires a single positive NAAT
          • in areas without SARS-CoV-2 circulation, requires ≥ 1 of
            • positive NAAT for ≥ 2 targets on the SARS-CoV-2 virus using a validated assay
            • 1 positive NAAT for betacoronavirus plus sequencing SARS-CoV-2 genome
        • discordant results between NAAT and sequencing should prompt resampling
        • negative results do not rule out COVID-19
        • additional sampling, including from lower respiratory tract should be considered in patients with a negative NAAT and high clinical suspicion
    • serologic assays are in development and paired serum samples (ideally 2-4 weeks apart) may be stored for future testing
    • whole genome sequencing can contribute to molecular epidemiology studies
    • viral culture not recommended as diagnostic procedure
    • laboratories should follow national reporting requirements
    • Reference - WHO Laboratory testing for 2019 novel coronavirus in suspected human cases 2020 Mar 19
  • Centers for Disease Control and Prevention (CDC) interim guidance for evaluation of patients under investigation (PUI)
    • sample collection
      • collect clinical specimens from PUIs for routine testing of respiratory pathogens at either clinical or public health labs
      • collect samples as soon as possible once PUI identified regardless of time since symptom onset
      • maintain proper infection control during collection
    • specimen types for initial diagnostic testing for COVID-19
      • upper respiratory nasopharyngeal swab recommended
      • other upper respiratory samples may include
        • oropharyngeal swab collected by healthcare professional (combined in same tube with nasopharyngeal swab if both collected)
        • nasopharyngeal wash/aspirate or nasal aspirate (2-3 mL submitted in sterile container)
        • nasal mid-turbinate (NMT) swab collected by healthcare professional or by onsite self-collection using a flocked tapered swab
        • anterior nares specimen collected by healthcare professional or by onsite self-collection using a flocked or spun polyester swab
      • lower respiratory specimens can be also be tested, if available, including
        • sputum from patients with productive cough
        • lower respiratory tract aspirate or bronchoalveolar lavage in patients for whom it is clinically indicated, such as those receiving mechanical ventilation
      • sputum induction not recommended
    • storage
      • store specimens at 2-8 degrees C (35.6-46.4 degrees F) for up to 72 hours
      • store at -70 degrees C (-94 degrees F) or below if a delay in testing or shipping is expected
    • Reference - CDC Interim guidelines for collecting, handling, and testing clinical specimens from persons for coronavirus disease 2019 (COVID-19) (2020 Apr 14
  • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations for laboratory diagnosis in the critical care setting
    • for intubated and mechanically ventilated adults with suspected COVID-19
      • obtaining lower respiratory tract samples recommended over upper respiratory tract (nasopharyngeal or oropharyngeal) samples (NIH Grade BII)
      • when obtaining lower respiratory samples, endotracheal aspirates recommended over bronchial wash or bronchoalveolar lavage samples (NIH Grade BII)
    • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)
  • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign recommendations for specimen collection in intubated and mechanically ventilated adults with suspected COVID-19
  • Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_DisordersFDA emergency use authorization issued for multiple new assays to detect nucleic acids from SARS-CoV-204/24/2020 04:03:13 PMFDA emergency use authorization for
  • FDA issues policy update on developing and authorizing tests for COVID-19 (FDA News Release 2020 Mar 16)

Blood Tests

  • serologic tests
    • Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_DisordersFDA issues letter to healthcare providers to reinforce limitations of serologic testing to detect COVID-19 (FDA Letter to healthcare providers 2020 Apr 17)04/24/2020 04:04:50 PMFDA issues letter to healthcare providers to reinforce limitations of serologic testing to detect COVID-19
      • no antibody test currently available for diagnosis of SARS-CoV-2 infection has been validated (to the knowledge of the FDA)
      • recommendations for clinicians
        • continue to use serologic tests as appropriate, with awareness of their limitations which include
          • antibody levels may not reach detectable levels, and duration for which antibodies (IgG and IgM) remain detectable is unknown
          • IgM antibodies do not always develop early (or at all) in active infection
          • IgG antibodies may take time to develop (typically 7-10 days after infection), but may not exclude patients with recent infection who are still contagious (especially with concurrent detection of IgM antibodies)
        • consider serologic testing to determine potential exposure rather than as sole basis to diagnose COVID-19
        • be aware that not all serologic tests on the market have been evaluated by the FDA
      • Reference - FDA Letter to healthcare providers 2020 Apr 17, Fact Sheet for healthcare providers 2020 Apr
    • tests authorized by FDA for emergency use to detect immune antibody response to COVID-19
  • Study Summary
    lymphopenia may be common in patients with COVID-19 pneumonia
    Details
    studySummary
    • Cohort StudyCohort StudyCohort StudyCohort Study based on 4 cohort studies
    • cohort admitted January 1-28, 2020
      • 138 adults aged 22-92 years (median age 56 years, 54% men) with confirmed COVID-19 pneumonia consecutively admitted to Zhongnan Hospital in Wuhan, China, between January 1-28, 2020, were evaluated through February 3, 2020
      • laboratory testing revealed
        • lymphopenia (lymphocyte count < 1.1 × 109 cells/L) in 70.3%
        • prolonged prothrombin time (> 12.5 seconds) in 58%
        • elevated lactate dehydrogenase (> 243 units/L) in 39.9%
      • PubMed32031570JAMAJAMA20200207Reference - JAMA 2020 Feb 7 early online, commentary can be found in JAMA 2020 Feb 5 early online
    • cohort admitted by January 2, 2020
      • 41 patients (mean age 49 years, 73% male) with confirmed COVID-19 pneumonia admitted to Jinyintan Hospital in Wuhan, China, by January 2, 2020, were evaluatedCritical_Care Infectious_Diseases Internal_Medicine Pulmonary_Disordersfever and cough most common clinical features in patients with 2019-nCoV pneumonia (Lancet 2020 Jan 24 early online)01/28/2020 08:59:32 AM
      • laboratory testing revealed
        • lymphopenia (lymphocyte count < 1 × 109 cells/L) in 63%
        • elevated aspartate aminotransferase levels in 37%
        • leukopenia (white blood cell count < 4 × 109 cells/L) in 25%
        • viremia in 15%
      • PubMed32004427The New England journal of medicineN Engl J Med20200131Reference - Lancet 2020 Feb 15;395(10223):497, correction can be found in Lancet 2020 Feb 15;395(10223):496
    • cohort admitted January 1-20, 2020
      • 99 adults aged 21-82 years (mean age 55 years, 68% men) with confirmed COVID-19 pneumonia admitted to Jinyintan Hospital in Wuhan, China, from January 1 to 20, 2020, were evaluated up to January 25, 2020
      • laboratory testing revealed
        • increased lactate dehydrogenase (> 250 units/L) in 76%
        • decreased hemoglobin (< 130 g/L) in 51%
        • neutrophilia (neutrophil count > 6.3 × 109 cells/L) in 38%
        • lymphopenia (lymphocyte count < 1.1 × 109 cells/L) in 35%
        • leukocytosis (white blood cell count > 9.5 × 109 cells/L) in 24%
        • thrombocytopenia (platelet count < 125 × 109 platelets/L) in 12%
        • leukopenia (white blood cell count < 3.5 × 109 cells/L) in 9%
        • thrombocytosis (platelet count > 350 × 109 platelets/L) in 4%
      • PubMed32007143Lancet (London, England)Lancet20200130Reference - Lancet 2020 Feb 15;395(10223):507
    • cohort admitted January 16-February 3, 2020
      • 140 adults (median age 57 years, range 25-87 years) with confirmed COVID-19 admitted to No. 7 Hospital of Wuhan from January 16 to February 3, 2020, were evaluated
      • laboratory testing revealed
        • elevated C-reactive protein in 91.9%
        • elevated serum amyloid A in 90.2%
        • lymphopenia in 75.4%
        • eosinopenia in 52.9%
        • elevated D-dimer in 43.2%
        • elevated procalcitonin in 34.7%
      • comparing patients with severe disease vs. nonsevere disease
        • median lymphocyte percentage 12.7% vs. 20% (p < 0.001)
        • median D-dimer 0.4 mcg/mL vs. 0.2 mcg/mL (p < 0.001)
        • median C-reactive protein 47.6 mg/L vs. 28.7 mg/L (p < 0.001)
        • median procalcitonin 0.1 ng/mL vs. 0.05 ng/mL (p < 0.001)
        • median leukocyte count 5.3 × 109 cells/L vs. 4.5 × 109 cells/L (p = 0.014)
      • PubMed32077115AllergyAllergy20200219Reference - Allergy 2020 Feb 19 early online

Imaging Studies

  • Study Summary
    chest computed tomography (CT) might help screen for COVID-19 in epidemic areas, but high false-positive rate may limit its utility
    DynaMed Level2
    Diagnostic Cohort Study: Radiology 2020 Feb 26 early online
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorderschest CT might help screen for COVID-19 in epidemic areas, but high false-positive rate may limit its utility (Radiology 2020 Feb 26 early online)03/20/2020 10:54:27 AMstudySummary
    • Diagnostic Cohort Study based on retrospective diagnostic cohort study with possible selection bias
    • 1,014 children and adults aged 2-95 years (mean age 51 years, 99% > 20 years old) suspected of COVID-19 infection in Wuhan, China, from January 6 to February 6, 2020, who had both chest CT and reverse transcriptase polymerase chain reaction (PCR) from swab samples (reference standard) were assessed
    • time interval between PCR and chest CT ≤ 7 days (median interval 1 day)
    • prevalence of COVID-19 was 59%
    • main positive chest CT findings were ground-glass opacity in 46% and consolidations in 50%; other findings included reticulation/thickened interlobular septa and nodular lesions
    • 90% had bilateral chest CT findings
    • diagnostic performance of chest CT for detection of COVID-19
      • sensitivity 97% (95% CI 95%-98%)
      • specificity 25% (95% CI 22%-30%)
      • positive predictive value 65% (95% CI 62%-68%)
      • negative predictive value 83% (95% CI 76%-89%)
    • PubMed32101510RadiologyRadiology20200226200642200642Reference - Radiology 2020 Feb 26 early online
  • Study Summary
    bilateral ground-glass opacities common finding on chest CT in patients with COVID-19 pneumonia
    Details
    Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disordersbilateral ground-glass opacities common finding on chest CT in patients with COVID-19 pneumonia (J Med Virol 2020 Apr 21 early online)04/27/2020 08:57:08 AMstudySummary
    • Systematic ReviewSystematic Review based on 2 systematic reviews
    • systematic review of 34 retrospective studies evaluating 4,121 patients with COVID-19 in China
      • all results limited by significant heterogeneity
      • distribution of lesions
        • bilateral lesions in 73.8% (95% CI 65.9%-81.1%) in analysis of 28 studies with 2,628 patients
        • multilobar lesions in 67.3% (95% CI 54.8%-78.8%) in analysis of 10 studies with 846 patients
        • single lesion in 18.7% (95% CI 14.7%-23.1%) in analysis of 22 studies with 1,977 patients
        • single lobe lesions in 14.9% (95% CI 9.2%-21.7%) in analysis of 9 studies with 629 patients
        • normal findings in 8.4% (95% CI 4.2%-13.9%) in analysis of 13 studies with 2,195 patients
      • lesion density
        • ground-glass opacities in 68.1% (95% CI 56.9%-78.2%) in analysis of 26 studies with 3,574 patients
        • air bronchogram sign in 44.7% (95% CI 32.9%-56.8%) in analysis of 15 studies with 1,075 patients
        • crazy paving pattern in 35.6% (95% CI 11.3%-64.8%) in analysis of 4 studies with 264 patients
        • consolidation in 32% (95% CI 21.5%-43.4%) in analysis of 14 studies with 1,637 patients
      • lesion shape
        • patchy in 40.3% (95% CI 29.8%-51.4%) in analysis of 8 studies with 2,009 patients
        • spider web sign in 39.5% (95% CI 27.2%-52.6%) in analysis of 11 studies with 806 patients
        • cord-like in 36.8% (95% CI 21.7%-53.4%) in analysis of 6 studies with 267 patients
        • nodular in 20.5% (95% CI 6.8%-39.1%) in analysis of 8 studies with 739 patients
      • accompanying signs
        • pleural thickening in 27.1% (95% CI 15.6%-40.5%) in analysis of 9 studies with 1,077 patients
        • lymphadenopathy in 5.4% (95% CI 2.2%-9.8%) in analysis of 8 studies with 622 patients
        • pleural effusion in 5.3% (95% CI 3.7%-7.3%) in analysis of 17 studies with 1,627 patients
      • PubMed32314805Journal of medical virologyJ Med Virol20200421Reference - J Med Virol 2020 Apr 21 early online
    • systematic review of 30 studies (19 cohort studies and 11 case reports) including 919 patients with COVID-19 were evaluated
      • common patterns and distribution on initial CT
        • ground-glass opacities in 88% in analysis of 22 studies with 393 patients
        • bilateral involvement in 87.5% in analysis of 12 studies with 497 patients
        • posterior involvement in 80.4% in 1 study with 51 patients
        • multilobar involvement in 78.8% in analysis of 5 studies with 137 patients
        • peripheral distribution in 76% in analysis of 12 studies with 121 patients
        • consolidation in 31.8% in analysis of 10 studies with 204 patients
      • PubMed32125873AJR. American journal of roentgenologyAJR Am J Roentgenol202003031-61Reference - AJR Am J Roentgenol 2020 Mar 14 early online
  • Study Summary
    ground-glass opacities evident on chest CT in about one-third of children with SARS-CoV-2 infection
    Details
    studySummary
    • Cohort Study based on retrospective cohort study
    • 171 children (median age 6 years, 61% male) with SARS-CoV-2 infection at Wuhan Children's Hospital between January 28 and February 26, 2020 were evaluated
    • spectrum of illness
      • pneumonia in 64.9% (111 children, of whom 12 had radiologic features of pneumonia without symptoms)
      • upper respiratory tract infection in 19.3% (33 children)
      • asymptomatic infection without radiologic features of pneumonia in 15.8% (27 children)
    • chest CT findings included
      • ground-glass opacity in 32.7%
      • local patchy shadowing in 18.7%
      • bilateral patchy shadowing in 12.3%
      • interstitial abnormalities in 1.2%
    • Reference - N Engl J Med 2020 Mar 18 early online
  • CT features by severity and stage of disease
    • Study Summary
      CT features may vary based on severity of disease in patients with COVID-19 pneumonia
      Details
      Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_DisordersCT features may vary based on severity of disease in patients with COVID-19 pneumonia (Eur Radiol 2020 Apr 11 early online)04/27/2020 08:58:37 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 120 patients (mean age 45 years, 64% female) with COVID-19 pneumonia admitted to single hospital in Wuhan, China, between January 10 and February 10, 2020, were evaluated
        • 16 patients were asymptomatic
        • 74 patients had mild-moderate disease
        • 30 patients had severe disease
      • comparing CT features in patients with mild-moderate disease vs. severe disease
        • bilateral involvement in 44% vs. 93% (p < 0.001)
        • ground-glass opacities in 87% vs. 97% (not significant)
        • nodules in 59% vs. 40% (p = 0.072)
        • linear densities in 56% vs. 83% (p = 0.007)
        • consolidation in 41% vs. 83% (p < 0.001)
        • crazy paving pattern in 10% vs. 70% (p < 0.001)
        • bronchiectasis in 7% vs. 27% (p = 0.007)
        • effusion in 0% vs. 30% (p < 0.001)
        • air bronchograms in 6% vs. 63% (p < 0.001)
        • white lung in 0% vs. 67% (p < 0.001)
        • involvement of all 5 lobes in 7% vs. 80% (p < 0.001)
        • tree-in-bud sign in 4% vs. 17% (p = 0.042)
      • comparing CT findings in patients with asymptomatic disease vs. findings in patients with symptoms, no significant difference in individual signs, patterns, zonal predominance, or extent of abnormalities
      • PubMed32279115European radiologyEur Radiol20200411Reference - Eur Radiol 2020 Apr 11 early online
    • Study Summary
      CT features may vary between early and advanced phases of COVID-19 pneumonia
      Details
      studySummaryCritical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersCT features may vary between early and advanced phases of COVID-19 pneumonia (AJR Am J Roentgenol 2020 Mar 5 early online)03/20/2020 10:56:34 AM
      • Cohort Study based on cohort study
      • 62 adults aged 30-77 years with laboratory-confirmed COVID-19 pneumonia in Wuhan, China, who had CT were evaluated
        • 40 patients had CT ≤ 7 days after onset of symptoms (early phase)
        • 22 patients had CT 8-14 days after onset of symptoms (advanced phase)
      • 83.9% had multiple lesions on CT overall; peripheral distribution of lesions in 77%, peripheral and central distribution in 23%
      • CT features comparing early vs. advanced phase
        • ground-glass opacities in 47.5% vs. 27.3% (p = 0.012)
        • ground-glass opacities plus reticular pattern in 50% vs 86.4% (p = 0.005)
        • vacuolar sign in 40% vs. 81.8% (p = 0.002)
        • fibrotic streaks in 42.5% vs. 81.8% (p = 0.003)
        • air bronchogram in 62.5% vs. 90.9% (p = 0.016)
      • rates of subpleural line, subpleural transparent line, bronchus distortion, and pleural effusion were significantly higher in advanced phase
      • no significant differences between early and advanced phases in consolidation, microvascular dilation sign
      • PubMed32134681AJR. American journal of roentgenologyAJR Am J Roentgenol202003051-81Reference - AJR Am J Roentgenol 2020 Mar 5 early online

Management

ManagementManagement

Management Overview

Supportive Management

Management of Hypoxemia and Acute Respiratory Distress Syndrome (ARDS)

  • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations for oxygenation and ventilation in the critical care setting
    • closely monitor patients receiving supplemental oxygen for worsening of respiratory status; early intubation by an experienced practitioner in a controlled setting recommended (NIH Grade AII)
    • high-flow nasal cannula (HFNC) recommended over noninvasive positive pressure ventilation (NIPPV) for adults with COVID-19 and acute hypoxemic respiratory failure despite conventional oxygen therapy (NIH Grade BI)
    • consider closely monitored trial of NIPPV for adults with COVID-19 and acute hypoxemic respiratory failure if HFNC is not available and endotracheal intubation not indicated (NIH Grade BIII)
    • for adults with ARDS receiving invasive mechanical ventilation,
      • low tidal volume (4-8 mL/kg) recommended over higher tidal volumes (> 8 mL/kg) (NIH Grade AI)
      • target plateau pressure of < 30 cm H2O (NIH Grade AII)
      • conservative fluid strategy recommended over liberal strategy (NIH Grade BII)
      • routine use of inhaled nitric oxide not recommended (NIH Grade AI)
    • for mechanically ventilated adults with COVID-19 and moderate-to-severe ARDS
      • higher positive end-expiratory pressure (PEEP) recommended over lower PEEP strategy (NIH Grade BII)
      • prone ventilation for 12-16 hours/day recommended over no prone ventilation for patients with refractory hypoxemia despite optimized ventilation (NIH Grade BII
    • use of neuromuscular blocking agents (NMBA)
      • intermittent boluses of NMBA or continuous NMBA infusion recommended to facilitate protective lung ventilation (NIH Grade BIII)
      • continuous NMBA infusion recommended for up to 48 hours in the event of persistent ventilator dyssynchrony as long as patient anxiety and pain can be adequately monitored and controlled (NIH Grade BIII)
    • for mechanically ventilated adults with COVID-19, severe ARDS, and refractory hypoxemia
      • consider recruitment maneuvers (NIH Grade CII), though staircase (incremental PEEP) not recommended (NIH Grade AII)
      • trial of inhaled pulmonary vasodilator as rescue therapy may be considered, but tapered off treatment if no rapid improvement is observed (NIH Grade CIII)
    • insufficient data to recommend for or against routine use of extracorporeal membrane oxygenation (ECMO) for patients with COVID-19 and refractory hypoxemia (NIH Grade BIII)
    • use of antimicrobials
      • insufficient data to recommend empiric broad-spectrum antimicrobial therapy in the absence of another indication (NIH Grade BIII)
      • if antimicrobials initiated, reevaluate use daily (NIH Grade AIII)
    • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)
  • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign guideline on management of critically ill adults with coronavirus disease 2019 (COVID-19) recommendations on ventilatory support
  • World Health Organization (WHO) interim guidance on management of severe acute respiratory infection when COVID-19 is suspected
    • oxygen therapy and monitoring
      • give supplemental oxygen immediately to patients with respiratory distress, hypoxemia, or shock and target peripheral oxygen saturation (SPO2) > 94%
      • closely monitor for signs of deterioration such as rapidly progressive respiratory failure and sepsis
      • tailor management of comorbid conditions and monitor for drug-drug interactions
      • use conservative fluid management when there is no evidence of shock as aggressive fluid therapy may worsen oxygenation
    • management of ARDS
      • recognize when patient is failing oxygen therapy with development of severe hypoxemic respiratory failure and prepare to provide advanced oxygen/ventilatory support
      • if endotracheal intubation is needed, it should be performed by trained and experienced provider using airborne precautions
      • in patients with ARDS treated with noninvasive or high-flow oxygen systems
        • high-flow nasal oxygen and noninvasive ventilation should be reserved for select patients with hypoxemic respiratory failure
        • closely monitored patients for deterioration
      • in mechanically ventilated patients with ARDS
        • use lower tidal volumes (4-8 mL/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H20)
        • in adults with severe ARDS, prone ventilation for 12-16 hours/day is recommended
          • considered prone positioning in children, but sufficient resources and expertise are required to safely perform
          • pregnant women may benefit from lateral decubitus position
        • use conservative fluid management in patients without tissue hypoperfusion to shorten duration of ventilation
        • in patients with moderate-severe ARDS
          • consider higher PEEP instead of lower PEEP
          • neuromuscular blockade by continuous infusion should not be routinely used
        • avoid disconnecting the patient from the ventilator
        • use in-line catheters for airway suctioning and clamp endotracheal tube when disconnection is required
      • consider referral of patients with refractory hypoxemia despite lung protective ventilation to ECMO center
    • Reference - World Health Organization interim guidance on management of severe acute respiratory infection when COVID-19 is suspected (WHO 2020 Mar 13)

  • CLINICIANS' PRACTICE POINT

    Intubating a COVID-19 patient is an aerosol generating procedure and precautions should be taken to maximize first attempt success and minimize exposure of health care personnel to the virus.
    • Prepare ahead with all required equipment in prepacked bundles. This should include a bag-mask with HEPA filter, ventilator tubing with in-line adaptors for suctioning and bronchoscopy (should that become necessary), wave form capnography, a smooth clamp for the endotracheal tube, and all medications drawn up and labeled in advance including induction agents for rapid sequence intubation (RSI), neuromuscular blocking agent, vasopressors, and isotonic saline.
    • Intubation should be performed with airborne precautions ideally in a negative pressure room and should be done by the most skilled intubator available to optimize first attempt success. The minimal number of health care workers needed should be in the intubation room with fully donned personal protective equipment (PPE) including either a fit-tested N95 mask or powered air-purifying respirator (PAPR) if available and typically would include the intubator, a nurse, and a respiratory therapist.
    • Use of a video laryngoscope with clear disposable cover is preferred and, if available, a transparent “aerosol box” can be used to cover the patient’s head allowing intubation via two circular ports to minimize aerosol exposure.
    • Bag-mask ventilation (BMV) should be avoided when possible; preoxygenation should be achieved via a non-rebreather mask with 100% oxygen for 3-5 minutes, if circumstances permit. Avoid nasal cannula for apneic oxygenation or high-flow oxygenation cannula.
    • Awake intubations should be avoided as cough will increase risk of viral spread. If unable to preoxygenate with above approach, non-invasive mask ventilation using a full-face mask with tight fit connected to a closed-circuit dual-limb ventilator with HEPA filters can be used; suspending the ventilator before removing mask for intubation is important to minimize aerosolization. If BMV must be employed, use of a 2-person thenar technique with lower volumes and an HEPA filter is advised.
    • Once intubation is achieved inflate cuff on endotracheal tube (ETT) immediately prior to initiating mechanical ventilation; check end-tidal CO2 to confirm placement, but then clamp the ETT before removing the colorimetric device. A HEPA filter should be in place between ETT and the ventilator. Limit ventilator disconnections and if disconnection is necessary, clamp the ETT and disconnect at end expiration.
    • The intubation procedure can be bundled with other procedures such as central venous catheter (CVC) placement with one chest x-ray to assess both ETT and CVC placement.
    • Minimize the ordering of chest x-rays and, when possible, use point-of-care ultrasound (POCUS) to assess for changes in clinical status (e.g. concern over pneumothorax, assessing for cardiac dysfunction, etc.).
    • Nebulizer treatments both on and off mechanical ventilation should be avoided. Use metered-dose inhalers (MDIs) with a spacer device in spontaneously breathing patients instead of nebulizers and use in-line MDI for those who absolutely require them on the ventilator.

  • see also

Management of Septic Shock

  • recognize septic shock
    • in adults with all of
      • suspected or confirmed infection
      • vasopressors needed to maintain mean arterial pressure (MAP) ≥ 65 mg Hg, AND lactate level is ≥ 2 mmol/L
      • absence of hypovolemia
    • in children with hypotension or ≥ 2 of
      • altered mental state
      • tachycardia or bradycardia
      • prolonged capillary refill > 2 seconds or feeble pulses
      • tachypnea
      • mottled skin or petechial or purpuric rash
      • increased lactate
      • oliguria
      • hyperthermia or hypothermia
    • Reference - World Health Organization interim guidance on management of severe acute respiratory infection when COVID-19 is suspected (WHO 2020 Mar 13)
  • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations for hemodynamic support in the critical care setting
    • fluid therapy
      • use of dynamic parameters, skin temperature, capillary refilling time, and/or lactate recommended over static parameters to assess fluid responsiveness (NIH Grade BII)
      • for acute resuscitation of adults with COVID-19 and shock
        • buffered/balanced crystalloids recommended over unbalanced crystalloids (NIH Grade BII)
        • initial use of albumin not recommended (NIH Grade BI)
        • do not use hydroxyethyl starches for intravascular volume replacement (NIH Grade AI)
    • vasoactive agents
      • norepinephrine first choice vasopressor (NIH Grade AII)
      • consider addition of
        • vasopressin (up to 0.03 units/minute) (NIH Grade BII) or epinephrine (NIH Grade CII) to raise mean arterial pressure to target
        • vasopressin (up to 0.03 units/minute) to decrease norepinephrine dosage (NIH Grade CII)
      • consider dopamine as alternative vasopressor agent in patients with low risk of tachyarrhythmias and absolute or relative bradycardia (NIH Grade BII)
      • low-dose dopamine not recommended for renal protection (NIH Grade BII)
      • dobutamine recommended in patients with evidence of persistent hypoperfusion despite adequate fluid loading and vasopressor use (NIH Grade BII)
      • placement of arterial catheter recommended as soon as practical for all patients who require vasopressors, if resources available (NIH Grade BIII)
    • low-dose corticosteroid therapy recommended for patients with COVID-19 and refractory shock (NIH Grade BII)
    • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)
  • SCCM Surviving Sepsis Campaign guideline on management of critically ill adults with coronavirus disease 2019 (COVID-19) recommendations on hemodynamic support
  • World Health Organization (WHO) interim guidance on management of severe acute respiratory infection when COVID-19 is suspected
    • antimicrobial therapy for patients with sepsis
      • start empiric antimicrobial therapy as soon as possible (within 1 hour of assessment) for patients with severe acute respiratory infection and sepsis
      • deescalate therapy based on microbiology and clinical judgement
    • resuscitation strategies for patients with septic shock
      • fluid resuscitation
        • in adults, give 250-500 mL crystalloid fluid as rapid bolus in first 15-30 minutes
        • in children, give 10-20 mL/kg crystalloid fluid as bolus in first 30-60 minutes
        • reassess for signs of fluid overload after each bolus
        • reduce or discontinue fluid if there is no response to fluid or signs of volume overload
        • avoid hypotonic crystalloids, starches, or gelatins
      • vasopressors
        • consider vasopressors
          • in adults, when shock persists during or after fluid resuscitation (target mean arterial pressure [MAP] ≥ 65 mm Hg and perfusion marker improvement)
          • in children, if any of
            • signs of shock persist after 2 repeat boluses
            • age-appropriate blood pressure targets are not achieved
            • signs of fluid overload are apparent
        • if central venous catheters are not available for vasopressor administration
          • peripheral IV may be used for vasopressor administration, but use a large vein and closely monitor for signs of extravasation and local tissue necrosis
          • administration through intraosseous needles is also possible
        • consider inotrope such as dobutamine if signs of poor perfusion and cardiac dysfunction persist despite achieving MAP target
    • Reference - World Health Organization interim guidance on management of severe acute respiratory infection when COVID-19 is suspected (WHO 2020 Mar 13)
  • see also Sepsis Treatment in Adults or Sepsis Treatment in Children

Use of Corticosteroids

  • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations for corticosteroid therapy
    • for critically ill patients with COVID-19
      • systemic corticosteroids not routinely recommended for mechanically ventilated patients without acute respiratory distress syndrome (ARDS) (NIH Grade BIII)
      • insufficient evidence to recommend for or against systemic corticosteroids in mechanically ventilated adults with ARDS in the absence of another indication (NIH Grade CI)
      • low-dose corticosteroid therapy recommended for patients with COVID-19 and refractory shock (NIH Grade BII)
    • for hospitalized, non-critically ill patients, routine use of systemic corticosteroids not recommended unless they are in the intensive care unit (NIH Grade AIII)
    • for patients taking corticosteroids for pre-existing conditions
      • oral corticosteroids should not be discontinued (NIH Grade AIII)
      • supplemental or stress-dose corticosteriods may be indicated on case-by-case basis (NIH Grade AIII)
      • inhaled corticosteroids for asthma and COPD should not be discontinued (NIH Grade AIII
    • NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)
  • Infectious Disease Society of America (IDSA) guideline on treatment and management of patients with COVID-19 recommendations on corticosteroids
  • SCCM Surviving Sepsis Campaign guideline on management of critically ill patients with COVID-19 recommendations on corticosteroids
  • WHO recommends to not routinely give systemic corticosteroids for treatment of viral pneumonia outside of clinical trials (WHO Clinical management of severe acute respiratory infection when COVID-19 is suspected 2020 Mar 13)
  • as PubMed32043983Lancet (London, England)Lancet2020021539510223473-475473no clinical data exist to support use of corticosteroid therapy in the treatment of respiratory infection due to SARS-CoV or MERS-CoV, patients with COVID-19 may also be unlikely to benefit from corticosteroid regimens (Lancet 2020 Feb 15;395(10223):473)

Use of Antipyretics

Other Management Considerations

  • considerations for patients with cardiovascular disease
    • Heart Failure Society of America/American College of Cardiology/American Heart Association (HFSA/ACC/AHA) statement regarding use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
      • no clinical or experimental data exists suggesting benefit or harm of renin-angiotensin-aldosterone system (RAAS) antagonists (including ACE inhibitors and ARBs) in patients with COVID-19
      • HFSA/ACC/AHA recommend continuation of these agents for indications with proven benefit including heart failure, hypertension, and ischemic heart disease
      • if patient with cardiovascular disease on RAAS antagonist is diagnosed with COVID-19, treatment decisions should be made based on individual patient's hemodynamic status and clinical presentation
      • Reference - ACC News Story 2020 Mar 17
    • National Institutes of Health (NIH) guideline on treatment of COVID-19
      • ACE inhibitors and ARBs
        • patients with COVID-19 taking ACE inhibitors or ARBs for cardiovascular disease or other indications should continue these medications (NIH Grade AIII)
        • for treatment of COVID-19, ACE inhibitors or ARBs not recommended outside of a clinical trial (NIH Grade AIII)
      • statins
        • patients with COVID-19 taking statins for treatment or prevention of cardiovascular disease should continue these medications (NIH Grade AIII)
        • for treatment of COVID-19, statins not recommended outside of a clinical trial (NIH Grade AIII)
      • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)
    • see COVID-19 and Cardiovascular Disease Patients for additional information
  • United States Department of Health and Human Services (DHHS) interim guidance for COVID-19 in persons with HIV infection recommendations on antiretroviral therapy
    • maintain at least 30-day on-hand supply (ideally 90-day supply) of antiretroviral drugs and other medication
    • discuss changing medication delivery to mail order (if possible) with pharmacist or healthcare provider
    • if regimen switch is planned, consider delaying switch until close monitoring and follow-up are possible
    • if protease inhibitors (PI) are not already part of the prescribed antiretroviral regimen, do not change the regimen to include a PI to prevent or treat COVID-19 unless this is done within clinical trial parameters or in consultation with HIV specialist
    • Reference - AIDSInfo 2020 Mar 20
    • see COVID-19 and Special Populations for additional information

Investigational Therapies

Hydroxychloroquine/chloroquine With or Without Azithromycin

  • guidance on use of hydroxychloroquine/chloroquine
    • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations on hydroxychloroquine and chloroquine
      • insufficient data to recommend for or against hydroxychloroquine or chloroquine (NIH Grade AIII)
      • if hydroxychloroquine or chloroquine used, monitor patient for adverse events including prolonged QT interval (NIH Grade AIII)
      • combination of hydroxychloroquine plus azithromycin not recommended except in the context of a clinical trial (NIH Grade AIII)
      • Reference - National Institutes of Health (NIH) COVID-19 Treatment Guideline (NIH 2020 Apr 21)
    • Infectious Disease Society of America (IDSA) guideline on treatment and management of patients with COVID-19 recommendations on hydroxychloroquine/chloroquine
      • hydroxychloroquine/chloroquine may be considered for hospitalized patients with COVID-19 in the context of a clinical trial (IDSA Knowledge gap)
      • hydroxychloroquine/chloroquine plus azithromycin may be considered for hospitalized patients with COVID-19 only in the context of a clinical trial (IDSA Knowledge gap)
      • Reference - IDSA guideline on management of patients with COVID-19 (IDSA 2020 Apr 11)
    • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign guideline on management of critically ill patients with COVID-19 finds insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine (Crit Care Med 2020 Mar 27 early onlinePDF, also published in Intensive Care Med 2020 Mar 28 early onlinefull-text)
    • FDA guidance
      • Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_DisordersFDA issues safety communication regarding hydroxychloroquine and chloroquine emergency use authorization for COVID-19 (FDA safety communication 2020 Apr 24)04/27/2020 04:30:50 PMFDA issues safety communication regarding hydroxychloroquine and chloroquine emergency use authorization for COVID-19
        • FDA warns against usage to treat non-hospitalized patients and reiterated use should be limited to hospitalized patients appropriately monitored
        • hydroxychloroquine and chloroquine may cause QT prolongation and ventricular tachycardia and ventricular fibrillation, which may increase when combined with azithromycin
        • clinicians considering hydroxychloroquine should first attempt to enroll patients into clinical trials
        • Reference - FDA safety communication 2020 Apr 24
      • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues Emergency Use Authorization permitting emergency usage of hydroxychloroquine sulfate from National Strategic Stockpile for treatment of COVID-19 in hospitalized adults and adolescents weighing ≥ 50 kg for whom clinical trials are not available or participation not feasible (FDA Fact Sheet 2020 Mar 28)04/01/2020 11:23:54 AMFDA issues Emergency Use Authorization (EUA) permitting emergency usage of hydroxychloroquine sulfate from National Strategic Stockpile for treatment of COVID-19 in hospitalized adults and adolescents weighing ≥ 50 kg for whom clinical trials are not available or participation not feasible
        • suggested dosing is 800 mg orally on day 1 and then 400 mg/day for 4-7 days of total treatment based on clinical evaluation
        • baseline electrocardiogram should be obtained to assess for QT prolongation; use with caution in patients with cardiac disease, QT prolongation, history of ventricular arrhythmias, bradycardia, uncorrected potassium or magnesium imbalance, or with concomitant administration of other QT interval prolonging drugs
        • contraindicated in patients with retinal or visual field changes of any etiology
        • consider risk vs. benefit before prescribing in pregnant women; although embryo-fetal developmental toxicity has been reported with supratherapeutic doses in animal studies, no increase in rate of birth defects or spontaneous abortions reported with therapeutic doses for malaria in observational clinical studies
        • Reference - FDA Fact Sheet 2020 Mar 28
      • use of hydroxychloroquine and chloroquine for COVID-19 patients under EUA
        • to request hydroxychloroquine or chloroquine for treatment of COVID-19, contact local or state health department
        • healthcare providers must
          • provide patients with EUA Fact Sheet for Patients and Parent/Caregivers for either hydroxychloroquine or chloroquine
          • inform patient of option to accept or refuse treatment with these agents as well as potential consequences of refusing therapy
          • explain known and potential risks and benefits of treatment as well as available alternative products and their risks and benefits
          • submit a report on all medication errors and all related serious adverse events
          • References - FDA Fact Sheet 2020 Mar 28, FDA Fact Sheet 2020 Mar 28
      • Drugs Family_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues Emergency Use Authorization permitting emergency usage of chloroquine phosphate for treatment of COVID-19 in hospitalized adults and adolescents weighing ≥ 50 kg for whom clinical trials are not available or participation not feasible (FDA Fact Sheet 2020 Mar 28)04/06/2020 05:12:38 PMFDA issues EUA permitting emergency usage of chloroquine phosphate for treatment of COVID-19 in hospitalized adults and adolescents weighing ≥ 50 kg for whom clinical trials are not available or participation not feasible
        • suggested dosing is 1 g orally on day 1, followed by 500 mg/day for 4-7 days of total treatment based on clinical evaluation
        • precautions, warnings, and adverse effects associated with chloroquine phosphate are similar to those of hydroxychloroquine
        • Reference - FDA Fact Sheet 2020 Mar 28
      • FDA issues safety communication about mistaking chloroquine phosphate intended for use in aquarium fish with the FDA-approved drug chloroquine phosphate and warns against taking any form of chloroquine unless prescribed by clinician (FDA MedWatch 2020 Mar 27, FDA Letter to Stakeholders 2020 Mar 27)
  • Study Summary
    hydroxychloroquine sulfate with or without azithromycin may increase viral clearance of SARS-CoV-2 within 6 days in adults with COVID-19
    DynaMed Level3
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordershydroxychloroquine sulfate with or without azithromycin may increase viral clearance of SARS-CoV-2 within 6 days in adults with COVID-19 (Int J Antimicrob Agents 2020 Mar 20 early online)04/03/2020 04:18:39 PMstudySummary
    • Nonrandomized Trial based on nonclinical outcomes in nonrandomized trial
    • 20 adults aged 20-87 years (mean age 51 years) with confirmed COVID-19 at 1 center in France received hydroxychloroquine sulfate 200 mg orally 3 times daily for 10 days and were compared to 16 patients aged 10-75 years (mean age 37 years) with confirmed COVID-19 who did not receive hydroxychloroquine treatment
      • at baseline, 61% had upper respiratory tract infection symptoms, 22% had lower respiratory tract infection symptoms, and 17% were asymptomatic
      • time from symptom onset to trial inclusion ranged from 1 to 10 days
      • 6 additional patients who started hydroxychloroquine were excluded for early cessation of treatment
    • 6 patients in hydroxychloroquine group also received azithromycin 500 mg orally on day 1 and then 250 mg/day for next 4 days
    • mean hydroxychloroquine serum concentration 0.46 mcg/mL
    • rates of virological clearance by day 6
      • 70% with hydroxychloroquine overall (p = 0.001 vs. controls, NNT 2)
        • 100% with hydroxychloroquine plus azithromycin (p < 0.001 vs. hydroxychloroquine only)
        • 57.1% hydroxychloroquine only
      • 12.5% in controls
    • adverse events not reported
    • PubMed32205204International journal of antimicrobial agentsInt J Antimicrob Agents20200320105949105949Reference - Int J Antimicrob Agents 2020 Mar 20 early onlinefull-text

Lopinavir/ritonavir

  • guidance on use of lopinavir/ritonavir
  • Study Summary
    addition of lopinavir/ritonavir to standard care may not shorten time to clinical improvement or decrease 28-day mortality in adults hospitalized with severe COVID-19
    DynaMed Level2
    Details
    Critical_Care Infectious_Diseases Internal_Medicine Pulmonary_Disordersaddition of lopinavir/ritonavir to standard care may not shorten time to clinical improvement or decrease 28-day mortality in adults hospitalized with severe COVID-19 (N Engl J Med 2020 Mar 18 early online)03/23/2020 12:18:10 PMstudySummary
    • Randomized Trial based on randomized trial without blinding and confidence intervals that cannot exclude differences that may be clinically important
    • 199 adults (median age 58 years, 60% men) hospitalized with severe COVID-19 were randomized to lopinavir/ritonavir 400 mg/100 mg orally twice daily for 14 days plus standard care vs. standard care alone
      • all patients had SARS-CoV-2 infection confirmed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, pneumonia confirmed by chest imaging, and oxygen saturation (SaO2) ≤ 94% with ambient air or ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300 mg Hg
      • median time between symptom onset and randomization was 13 days
    • clinical improvement assessed by 7-category ordinal scale with 1 indicating not hospitalized with resumption of normal activities, 2 not hospitalized but unable to resume normal activities, 3 hospitalized and not requiring supplemental oxygen, 4 hospitalized needing supplemental oxygen, 5 hospitalized needing nasal high-flow oxygen or noninvasive mechanical ventilation, 6 hospitalized and needing extracorporeal membrane oxygenation or invasive mechanical ventilation, and 7 death
    • time to clinical improvement defined as time from randomization to improvement by 2 categories on assessment scale or hospital discharge (whichever came first)
    • 95% in lopinavir/ritonavir group received treatment, 100% included in analysis
    • at baseline, 14% had clinical category 3, 70% had category 4, and 16% had category 5
    • 28-day outcomes comparing lopinavir/ritonavir vs. control
      • median time to clinical improvement 16 days vs. 16 days (hazard ratio 1.31, 95% CI 0.95-1.8), not significant, but CI cannot exclude differences that may be clinically important
      • mortality 19.2% vs. 25% (95% CI for difference -17.3% to +5.7%), not significant, but CI cannot exclude differences that may be clinically important
      • clinical improvement in 78.8% vs. 70% (95% CI for difference -3.3% to +20.9%)
      • median length of intensive care unit stay 6 days vs. 11 days (95% CI for difference 0 to -9 days)
      • median duration of invasive mechanical ventilation 4 days vs. 5 days (95% CI for difference -4 to +2 days)
      • serious grade 3-4 adverse event in 17.9% vs. 31.3% (no p values reported)
        • respiratory failure or acute respiratory distress syndrome (ARDS) in 12.6% vs. 27.3%
        • acute kidney injury in 2.1% vs. 5.1%
        • secondary infection in 1.1% vs. 6.1%
      • any grade 3-4 adverse event in 21.1% vs. 11.1% (no p values reported)
        • lymphopenia in 12.6% vs. 5.1%
        • anemia in 2.1% vs. 4%
    • PubMed32187464The New England journal of medicineN Engl J Med20200318Reference - LOTUS China trial (N Engl J Med 2020 Mar 18 early online)
  • Study Summary
    arbidol monotherapy associated with shorter duration of viral RNA positivity compared to lopinavir/ritonavir in patients with COVID-19
    DynaMed Level3
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersarbidol monotherapy associated with shorter duration of viral RNA positivity compared to lopinavir/ritonavir in patients with COVID-19 (J Infect 2020 Apr 10 early online)04/16/2020 10:15:21 AMstudySummary
    • Cohort Study based on retrospective cohort study with nonclinical outcomes
    • 50 patients with COVID-19 in 2 hospitals in China had arbidol 200 mg 3 times daily or lopinavir/ritonavir 400 mg/100 mg twice daily for 1 week
      • all patients had supportive oxygen therapy and atomized inhalation of recombinant human interferon-a2b 5 million units twice daily
      • no patients developed severe pneumonia or ARDS
    • comparing arbidol vs. lopinavir/ritonavir
      • detectable viral load at day 14 in 0% vs. 44.1% (p < 0.01)
      • median duration of viral RNA positivity 9.5 days vs. 11.5 days (p < 0.01)
    • PubMed32283143The Journal of infectionJ Infect20200410Reference - J Infect 2020 Apr 10 early online

Remdesivir

  • National Institutes of Health (NIH) guideline on treatment of COVID-19 finds insufficient data to recommend for or against remdesivir (NIH Grade AIII) (NIH 2020 Apr 21)
  • Study Summary
    remdesivir reported to have clinical improvement rate of 68% in adults hospitalized with severe COVID-19
    DynaMed Level3
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersremdesivir reported to have clinical improvement rate of 68% in adults hospitalized with severe COVID-19 (N Engl J Med 2020 Apr 10 early online)04/15/2020 09:08:31 AMstudySummary
    • Case Series based on case series
    • 53 adults (median age 64 years, 75% men) hospitalized with severe COVID-19 had remdesivir 200 mg IV on day 1 followed by 100 mg IV daily for 9 days
      • all patients had SARS-CoV-2 infection confirmed by RT-PCR and had oxygen saturation ≤ 94% with ambient air or oxygen support
      • mechanical ventilation in 57% and extracorporeal membrane oxygenation in 8% at baseline
    • clinical improvement defined as ≥ 2-point reduction in score on 6-point ordinal scale ranging from 1 (not hospitalized) to 6 (death) or survival to hospital discharge
    • median duration of invasive mechanical ventilation was 2 days
    • 75% of patients completed 10 days of treatment
    • during median follow-up of 18 days
      • clinical improvement in 68%
      • hospital discharge in 47%
      • mortality 13%
      • adverse events (increased hepatic enzymes, diarrhea, rash, renal impairment, and hypotension) in 60%
      • serious adverse events (multiple organ dysfunction syndrome, septic shock, acute kidney injury, and hypotension) in 23%
      • extubation in 57% of patients on mechanical ventilation
    • PubMed32275812The New England journal of medicineN Engl J Med20200410Reference - N Engl J Med 2020 Apr 10 early online

Convalescent Plasma and Other Blood Products

  • convalescent plasma
    • guidance on use of convalescent plasma
      • National Institutes of Health (NIH) guideline on treatment of COVID-19 finds insufficient data to recommend for or against convalescent plasma or hyperimmune immunoglobulin (NIH Grade AIII) (NIH 2020 Apr 21)
      • Infectious Disease Society of America (IDSA) guideline on treatment and management of patients with COVID-19 recommends convalescent plasma for hospitalized patients with COVID-19 in the context of a clinical trial (IDSA Knowledge gap) (IDSA 2020 Apr 11)
      • Society of Critical Care Medicine (SCCM) guideline on management of critically ill patients with coronavirus disease 2019 (COVID-19) does not recommend routine use of convalescent plasma (SCCM Weak recommendation, Low-quality evidence) because lack of efficacy in 1 trial (Crit Care Med 2020 Mar 27 early onlinePDF, also published in Intensive Care Med 2020 Mar 28 early onlinefull-text)
      • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA authorizes investigational usage of convalescent plasma through single-patient emergency Investigational New Drug process in patients with severe or immediately life-threatening COVID-19 infections (FDA Investigational New Drug Communication 2020 Mar 26)04/01/2020 11:25:53 AMFDA authorizes investigational usage of convalescent plasma through single-patient emergency Investigational New Drug (eIND) process in patients with severe or immediately life-threatening COVID-19 infections
        • convalescent plasma is authorized for investigational use through either the single-patient eIND pathway for individual patients or by submitting requests through the traditional IND regulatory pathway used in clinical trials
        • convalescent plasma is collected from patients who have recovered from COVID-19 and may contain antibodies to SARS-CoV-2 virus; administering this plasma to severely ill patients with COVID-19 infection may provide therapeutic benefit
        • indicated for treatment of laboratory-confirmed COVID-19 characterized as severe (with dyspnea, respiratory rate ≥ 30 breaths/minute, blood oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, and/or lung infiltrates > 50% within 24 to 48 hours) or immediately life-threatening (with respiratory failure, septic shock, and/or multiple organ dysfunction/failure)
        • plasma may only be collected from recovered individuals who are eligible to donate blood in addition to other required criteria (see FDA communication for details)
        • Reference - FDA Investigational New Drug Communication 2020 Mar 26
    • efficacy of convalescent plasma
      • Study Summary
        convalescent plasma transfusion reported to improve symptoms and pulmonary lesions in patients with severe COVID-19
        DynaMed Level3
        Details
        Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersconvalescent plasma transfusion reported to improve symptoms and pulmonary lesions in patients with severe COVID-19 (Proc Natl Acad Sci U S A 2020 Apr 6 early online)04/08/2020 05:15:25 PMstudySummary
        • Case Series based on case series
        • 10 adults (median age 52 years) with severe COVID-19 in 3 hospitals in China had convalescent plasma transfusion (200 mL plasma with neutralizing antibody > 1:640) at median 16.5 days after symptom onset in addition to supportive care and antiviral therapy
          • inclusion criteria included ≥ 1 of
            • respiratory distress (respiratory rate ≥ 30 beats/minute)
            • resting oxygen saturation < 93%
            • partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mm Hg
          • antiviral therapy included
            • arbidol with or without remdesivir, ribavirin, interferon-alfa, oseltamivir, and/or peramivir in 9 patients
            • ribavirin monotherapy in 1 patient
          • 6 patients had methylprednisolone 20 mg/day IV
          • 8 patients had antibiotic or antifungal treatment for coinfection
        • outcomes after convalescent plasma transfusion
          • improvement in symptoms in all patients 1-3 days post transfusion
          • improvement in pulmonary lesions on chest computed tomography in all patients
          • successful weaning from mechanical ventilation in 2 of 3 patients
          • increased lymphocyte count in 7 of 10 patients
          • undetectable SARS-CoV-2 RNA in 7 of 7 patients with detectable level before transfusion
        • PubMed32253318Proceedings of the National Academy of Sciences of the United States of AmericaProc Natl Acad Sci U S A20200406Reference - Proc Natl Acad Sci U S A 2020 Apr 6 early online
      • Study Summary
        convalescent plasma transfusion reported to resolve ARDS in 4 of 5 critically ill adults with confirmed COVID-19, with weaning from mechanical ventilation in 3 patients within 2 weeks of transfusion
        DynaMed Level3
        Details
        Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersconvalescent plasma transfusion reported to resolve acute respiratory distress syndrome in 4 of 5 critically ill adults with confirmed COVID-19, with weaning from mechanical ventilation in 3 patients within 2 weeks of transfusion (JAMA 2020 Mar 27 early online)04/01/2020 11:26:58 AMstudySummary
        • Case Series based on case series
        • 5 critically ill adults aged 36-65 years in Shenzhen, China, with confirmed COVID-19 and ARDS and who had severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment received convalescent plasma transfusion at 10-22 days after hospital admission
          • all patients had PaO2/FiO2 < 300 mg Hg and were on mechanical ventilation
          • transfused convalescent plasma was obtained from 5 patients who had recovered from COVID-19 and had SARS-CoV-2-specific antibody (IgG) binding titer > 1:1,000 and neutralization titer > 40
        • outcomes after convalescent plasma transfusion
          • 4 patients (80%) had resolution of ARDS at 12 days and normalization of body temperature within 3 days
          • 3 patients (60%) were weaned from mechanical ventilation within 2 weeks and were discharged from hospital
          • 2 patients remained hospitalized in stable condition at 37 days after transfusion
        • PubMed32176248JAMA internal medicineJAMA Intern Med20200316Reference - JAMA 2020 Mar 27 early online
      • Study Summary
        convalescent plasma transfusion reported to resolve SARS-CoV-2 infection in critically ill patients
        DynaMed Level3
        Details
        Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersconvalescent plasma transfusion reported to resolve SARS-CoV-2 infection in critically ill patients (Chest 2020 Mar 31 early online)04/15/2020 09:09:35 AMstudySummary
        • Case Report based on case report of 4 patients
        • 4 critically ill adults aged 31-73 years (including 1 pregnant woman) in China with SARS-CoV-2 infection received convalescent plasma transfusion 200-400 mL
        • first convalescent plasma transfusion at 11-19 days after admission (2 patients had multiple transfusions)
        • all patients were receiving supportive care, which included treatment with antiviral drugs, corticosteroids, and mechanical ventilation
        • all patients had ≥ 2 negative RT-PCR tests with first negative test at 3 to 22 days after transfusion
          • 3 patients were discharged
          • 1 patient was admitted to intensive care with multiple organ failure after negative tests
        • no serious adverse reactions to transfusion reported
        • PubMed32243945ChestChest20200331Reference - Chest 2020 Mar 31 early online
  • IV immunoglobulin (IVIG)
    • Society of Critical Care Medicine (SCCM) guideline on management of critically ill patients with coronavirus disease 2019 (COVID-19) does not recommend routine use routine use of IVIG (SCCM Weak recommendation, Low-quality evidence) because standard IVIG preparations are unlikely to have a biologic effect on SARS-CoV-2 (Crit Care Med 2020 Mar 27 early onlinePDF, also published in Intensive Care Med 2020 Mar 28 early onlinefull-text)
    • Study Summary
      in addition to multiple other interventions, IVIG within 48 hours of intensive care unit (ICU) admission associated with reduced mortality in patients with severe or critical COVID-19 compared to IVIG started later than 48 hours
      DynaMed Level2
      Details
      Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersin addition to multiple other interventions, IVIG within 48 hours of ICU admission associated with reduced mortality in patients with severe or critical COVID-19 compared to IVIG started later than 48 hours (J Infect 2020 Apr 10 early online)04/16/2020 10:16:43 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 58 patients (mean age 62 years, 62% male) with severe or critical COVID-19 pneumonia admitted to ICU at Wuhan Third Hospital had IVIG when absolute lymphocyte count < 0.5 × 109 cells/L
        • all patients had oxygen therapy and antiviral treatment
        • patients had moxifloxacin according to clinical symptoms and laboratory results
        • low-molecular-weight heparin was provided according to patient condition
        • patients with lymphocyte count < 0.5 × 109 cells/L for 5 days had thymosin
        • patients in critical condition had glucocorticoids 1-2 mg/kg for 5-7 days
      • comparing patients with IVIG within 48 hours of ICU admission vs. > 48 hours after ICU admission
        • death within 28 days in 7 patients vs. 16 patients (p = 0.009)
        • duration of hospital stay 11.5 days vs. 17 days (p = 0.006)
        • duration of ICU stay 9.5 days vs. 13.5 days (p = 0.045)
        • mechanical ventilation required by 6.7% vs. 32.1% (p = 0.016)
      • PubMed32283154The Journal of infectionJ Infect20200410Reference - J Infect 2020 Apr 10 early online

Other Agents in Clinical Trials

  • recommendations for other agents
    • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations for pharmacologic interventions
      • insufficient data to recommend for or against
      • interferons and janus kinase inhibitors not recommended outside of a clinical trial (NIH Grade AIII)
      • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)
    • Infectious Disease Society of America (IDSA) guideline on treatment and management of patients with COVID-19 recommends tocilizumab for hospitalized patients with COVID-19 only in the context of a clinical trial (IDSA Knowledge gap) (IDSA 2020 Apr 11)
    • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign guideline on management of critically ill adults with coronavirus disease 2019 (COVID-19) recommendations on COVID-19 therapies
  • medications under investigation
    • investigational antiviral agents include
      • favipiravir 1,600-2,400 mg loading dose followed by 600-1,200 mg twice daily for 7 days in clinical trials with or without tocilizumab
      • oseltamivir (neuraminidase inhibitor) 150-300 mg/day for 14 days in clinical trials with or without ritonavir or ASC09F
      • darunavir/cobicistat (antiretroviral) 800 mg/150 mg (1 tablet)/day for 5 days in clinical trial
    • other investigational agents include
      • sildenafil 0.1 g/day for 14 days in clinical trial
      • bevacizumab 500 mg IV for ≥ 90 minutes in clinical trial
      • thalidomide 100 mg orally every night for 14 days in clinical trial
      • methylprednisolone 1 mg/kg/day IV for 7 days in clinical trials
      • tocilizumab 4-8 mg/kg IV in clinical trials, maximum 800 mg per dose, with possible repeat dose in 12 hours
      • losartan 25 mg/day orally in clinical trials
      • eculizumab 900 mg IV weekly for 4 weeks followed by 1,200 mg IV every 2 weeks until recovery in clinical trial
      • mepolizumab 10 mg/day IV for 2 days in clinical trial
      • fingolimod 0.5 mg/day orally for 3 days in clinical trial
      • Huaier granule
      • traditional Chinese medicines
      • PUL-042
      • mesenchymal stem cells
      • tetrandrine
      • carrimycin
      • bromhexine hydrochloride
      • recombinant human interferon
      • Yinhu Qingwen granula
      • T89
      • anti-programmed death-1 (anti-PD-1)
      • aviptadil
      • nitric oxide
      • N-acetylcysteine plus Fuzheng Huayu
      • natural killer cells
      • deferoxamine
      • oral nutrition supplement enriched in eicosapentaenoic acid, gamma-linolenic acid, and antioxidants
      • DAS181
      • IFX-1
      • ciclesonide 320 mcg oral inhalation every 12 hours for 14 days in clinical trial
      • sarilumab 200-400 mg subcutaneously or IV
      • anakinra with or without siltuximab or tocilizumab
      • siltuximab
      • sargramostim
      • recombinant human angiotensin-converting enzyme 2 (RhACE2)
      • clevudine 120 mg once daily for 14-21 days in clinical trial
      • hyperbaric oxygen therapy
      • dapagliflozin 10 mg once daily for 30 days
      • dietary supplement with resistant potato starch
      • ruxolitinib 10 mg twice daily for 14 days in clinical trial
      • baricitinib 2 mg/day orally for 10-14 days in clinical trials
      • acalabrutinib
      • umifenovir
      • camostat mesylate 200-400 mg orally 3 times daily for 5-7 days in clinical trial
      • CAP-1002 allogeneic cardiosphere-derived cells
      • telmisartan 80 mg twice daily in clinical trial
    • list of COVID-19 related clinical trials can be found at ClinicalTrials.gov

Other Investigational Therapies

  • FDA issues Emergency Use Authorization permitting emergency usage of a blood purification system for treatment of confirmed COVID-19 in adults admitted to the intensive care unit with confirmed or imminent respiratory failure
    • the blood purification system works by filtering blood to help remove cytokines and other inflammatory mediators involved in cellular immune response and then returning filtered blood to patient
    • proteins that are removed may be associated with "cytokine storm" which can develop during infections (including COVID-19) and may lead to severe inflammation, rapidly progressive shock, respiratory failure, organ failure, and/or death
    • Reference - FDA press release 2020 Apr 10

Complications

  • Study Summary
    acute respiratory distress syndrome (ARDS) most common complication of COVID-19
    Details
    studySummary
    • Cohort StudyCohort StudyCohort Study based on 3 cohort studies
    • cohort admitted to Zhongnan Hospital in Wuhan, China January 1-28, 2020
      • 138 adults aged 22-92 years (median age 56 years, 54% men) with confirmed COVID-19 pneumonia consecutively admitted to Zhongnan Hospital in Wuhan, China, from January 1-28, 2020, were evaluated through February 3, 2020
      • complications included
        • ARDS in 19.6%
        • arrhythmia in 16.7%
        • shock in 8.7%
        • acute cardiac injury in 7.2%
        • acute kidney injury in 3.6%
      • PubMed32031570JAMAJAMA20200207Reference - JAMA 2020 Feb 7 early online, commentary can be found in JAMA 2020 Feb 5 early online
    • cohort admitted to Jinyintan Hospital in Wuhan, China by January 2, 2020
      • 41 patients (mean age 49 years, 73% male) with confirmed COVID-19 pneumonia admitted to Jinyintan Hospital in Wuhan, China, by January 2, 2020, were evaluated
      • complications included
        • ARDS in 29%
        • acute cardiac injury in 12%
        • secondary infection in 10%
      • PubMed31986264Lancet (London, England)Lancet2020021539510223497-506497Reference - Lancet 2020 Feb 15;395(10223):497, correction can be found in Lancet 2020 Feb 15;395(10223):496
    • cohort admitted to Jinyintan Hospital in Wuhan, China from January 1-20, 2020
      • 99 adults aged 21-82 years (mean age 55 years, 68% men) with confirmed COVID-19 pneumonia admitted to Jinyintan Hospital in Wuhan, China, from January 1-20, 2020, were evaluated up to January 25, 2020
      • complications included
        • ARDS in 17%
        • ventilator-associated pneumonia in 11%
        • acute respiratory injury in 8%
        • septic shock in 4%
        • acute kidney injury in 3%
      • PubMed32007143Lancet (London, England)Lancet20200130Reference - Lancet 2020 Feb 15;395(10223):507
  • neurologic complications
    • encephalitis
      • meningitis/encephalitis reported in 24-year old man with COVID-19 in case report, with SARS-CoV-2 RNA identified in cerebrospinal fluid (Int J Infect Dis 2020 Apr 3 early online)
      • PubMed32220634Travel medicine and infectious diseaseTravel Med Infect Dis20200324101642101642encephalitis reported in 56-year-old patient with COVID-19 in case report, with SARS-CoV-2 RNA identified in cerebrospinal fluid (Travel Med Infect Dis 2020 Mar 24 early online)
      • PubMed32283294Brain, behavior, and immunityBrain Behav Immun20200410encephalitis reported in man with COVID-19 in case report, although SARS-CoV-2 not identified in cerebrospinal fluid (Brain Behav Immun 2020 Apr 1 early online)
    • acute necrotizing hemorrhagic encephalopathy reported in woman with COVID-19 and altered mental status in case report (Radiology 2020 Mar 31 early online)
    • PubMed32303650NeurologyNeurology20200417Miller Fisher syndrome and polyneuritis cranialis each reported in 1 patient with COVID-19 in case series (Neurology 2020 Apr 17 early online)
  • cardiac complications
  • hematologic complications
    • PubMed32268022The New England journal of medicineN Engl J Med20200408coagulopathy, antiphospholipid antibodies, and multiple infarcts reported in 69-year old man with COVID-19 and history of hypertension, diabetes, and stroke in case series (N Engl J Med 2020 Apr 8 early online)
    • PubMed32306290Journal of thrombosis and thrombolysisJ Thromb Thrombolysis20200418venous thrombosis and arteriosclerosis obliterans of lower extremity reported in 69-year old man with COVID-19 in case report (J Thromb Thrombolysis 2020 Apr 18 early online)
  • PubMed32197060Emerging infectious diseasesEmerg Infect Dis20200320267acute pulmonary embolism reported in 60-year old man with COVID-19 in case report (Diagn Interv Imaging 2020 Apr 10 early onlinefull-text)
  • rhabdomyolysis with lower limb pain and fatigue reported in 60-year old man with COVID-19 in case report (Emerg Infect Dis 2020 Mar 20;26(7):doi:10.3201/eid2607.200445full-text)
  • PubMed32265202The British journal of ophthalmologyBr J Ophthalmol20200407bilateral acute conjunctivitis reported in 30-year old man with COVID-19 in case report (Br J Ophthalmol 2020 Apr 7 early online)

Prognosis

Mortality

  • China
    • Study Summary
      overall mortality 2.3% for earliest patients with COVID-19 in China, with higher mortality in patients with advanced age
      Details
      Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersoverall mortality rate 2.3% for earliest patients with COVID-19 in China, with higher mortality in patients with advanced age (Zhonghua Liu Xing Bing Xue Za Zhi 2020 Feb 17)03/04/2020 09:56:19 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 44,672 patients with confirmed COVID-19 with symptom onset between December 8, 2019 and February 11, 2020, in China's Infectious Disease Information System were evaluated
      • 1,023 patients died (overall mortality 2.3%)
      • mortality by age
        • 14.8% in patients ≥ 80 years old
        • 8% in patients aged 70-79 years
        • 3.6% in patients aged 60-69 years
        • 1.3% in patients aged 50-59 years
        • 0.4% in patients aged 40-49 years
        • 0.2% in patients aged 30-39 years
        • 0.2% in patients aged 20-29 years
        • 0.2% in patients aged 10-19 years
        • 0% in patients aged 0-9 years
      • mortality by comorbid conditions
        • 10.5% in patients with cardiovascular disease
        • 7.3% in patients with diabetes
        • 6.3% in patients with chronic respiratory disease
        • 6% in patients with hypertension
        • 5.6% in patients with cancer
        • 0.9% in patients without comorbid condition
      • PubMed32064853Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhiZhonghua Liu Xing Bing Xue Za Zhi20200217412145-151145Reference - Zhonghua Liu Xing Bing Xue Za Zhi 2020 Feb 17;41(2):145 [Chinese], also published in China CDC Weekly 2020;2(8):113 [English]
    • Study Summary
      acute respiratory distress syndrome and sepsis reported in 100% of patients with confirmed COVID-19 who died
      Details
      Critical_Care Hospital_Medicine Infectious_Diseases Pulmonary_Disorders Internal_Medicineacute respiratory distress syndrome and sepsis reported in 100% of patients with confirmed COVID-19 who died (BMJ 2020 Mar 26)04/02/2020 03:25:04 PMstudySummary
      • Cohort Study based on cohort study
      • 799 patients admitted to hospital designated for severely or critically ill patients with COVID-19 in China from January 13 to February 12, 2020, were followed until February 28, 2020
        • 14.1% died
        • 20.2% recovered and were discharged
        • 65.7% remained in hospital
      • median time from onset of symptoms to death was 16 days, and median time from onset of symptoms to discharge was 26 days
      • comparing patients who died vs. patients who recovered (no p values reported)
        • characteristics at baseline
          • median age 68 years vs. 51 years
          • ≥ 60 years old in 83% vs. 37%
          • male gender in 73% vs. 55%
          • ≥ 1 chronic medical condition in 63% vs. 39%
            • hypertension in 48% vs. 24%
            • diabetes in 21% vs. 14%
            • cardiovascular disease in 14% vs. 4%
            • chronic lung disease in 10% vs. 4%
            • cerebrovascular disease in 4% vs. 0%
            • chronic kidney disease in 4% vs. 1%
        • symptoms
          • dyspnea in 62% vs. 31%
          • chest tightness in 49% vs. 30%
          • disorder of consciousness in 22% vs. 1%
        • vital signs on admission
          • arterial pressure ≥ 140 mm Hg in 44% vs. 20%
          • heart rate > 100 beats per minute in 50% vs. 30%
          • respiratory rate ≥ 24 breaths per minute in 58% vs. 13.8%
          • percutaneous oxygen saturation ≤ 93% in 64% vs. 12%
        • laboratory findings
          • leukocytosis (≥ 10 × 109 cells/L) in 50% vs. 4%
          • lymphopenia (< 1 × 109 cells/L) in 91% vs. 47%
          • severe lymphopenia (< 0.5 × 109 cells/L) in 39% vs. 5%
          • hypoalbuminemia (albumin < 32 g/L) in 65% vs. 14%
          • elevated aspartate aminotransferase (> 40 units/L) in 52% vs. 16%
          • elevated cardiac troponin I (> 15.6 pg/mL) in 72% vs. 14%
          • elevated N-terminal pro-brain natriuretic peptide (> 285 pg/mL) in 85% vs. 18%
          • elevated D-dimer (> 21 mcg/mL) in 35% vs. 2%
        • complications
          • acute respiratory distress syndrome in 100% vs. 52%
          • sepsis in 100% vs. 41%
          • acute cardiac injury in 77% vs. 17%
          • type I respiratory failure in 51% vs. 0%
          • heart failure in 49% vs. 3%
          • alkalosis in 40% vs. 16%
          • hyperkalemia in 37% vs. 14%
          • acute kidney injury in 25% vs. 1%
          • hypoxic encephalopathy in 20% vs. 1%
      • PubMed32217556BMJ (Clinical research ed.)BMJ20200326368m1091m1091Reference - BMJ 2020 Mar 26;368:m1091full-text
  • United States
    • Study Summary
      case fatality rate 33.7% reported among nursing facility residents in King County, Washington
      Details
      Family_Medicine Geriatrics Infectious_Diseases Internal_Medicine Primary_Carecase fatality rate 33.7% reported among nursing facility residents in King County, Washington (N Engl J Med 2020 Mar 27 early online)04/01/2020 10:11:24 AMstudySummary
      • Cohort Study based on cohort study
      • 167 patients (median age 83 years) with confirmed COVID-19 associated with skilled nursing facility in Washington state, United States, from February 28 to March 18, 2020, were assessed
        • 101 residents of facility
        • 50 healthcare personnel
        • 16 visitors
      • most cases had respiratory illness, and 7 cases had no symptoms
      • 33.7% case fatality rate for nursing facility residents (34 of 101 residents)
      • hospitalization rates
        • 54.5% for facility residents
        • 6% for staff
        • 50% for visitors
      • PubMed32220208The New England journal of medicineN Engl J Med20200327Reference - N Engl J Med 2020 Mar 27 early online
    • Study Summary
      50% mortality reported in adults with confirmed COVID-19 admitted to intensive care units in Seattle, Washington, area
      Details
      Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorders50% mortality reported in adults with confirmed COVID-19 admitted to intensive care units in Seattle, Washington, area (N Engl J Med 2020 Mar 30 early online)04/08/2020 08:46:25 AMstudySummary
      • Cohort Study based on retrospective cohort study
      • 24 adults aged 23-97 years (mean age 64 years, 63% male) with confirmed COVID-19 admitted to intensive care units in Seattle, Washington, area between February 24 and March 9, 2020, were assessed for ≥ 14 days
        • mean duration of symptoms before hospital admission was 7 days
        • 22% were current or former tobacco smoker
      • coexisting medical conditions included
        • diabetes mellitus in 58%
        • chronic kidney disease in 21%
        • obstructive sleep apnea in 21%
        • asthma in 14%
        • chronic obstructive pulmonary disease in 4%
      • symptoms on admission included
        • cough in 88%
        • shortness of breath in 88%
        • sputum production in 42%
        • fever in 50%
        • rhinorrhea in 17%
        • sore throat in 8%
      • therapies included
        • invasive mechanical ventilation in 75%
        • vasopressors in 71%
        • high-flow nasal cannula in 42%
        • inhaled pulmonary vasodilators in 28%
      • outcomes at ≥ 14 days
        • overall in-hospital mortality 50%
        • in-hospital mortality in patients ≤ 65 years old 37%
        • hospital discharge in 21%
        • extubation in 33%
        • median length of hospital stay in survivors 17 days
        • median length of intensive care unit stay in survivors 14 days
        • median duration of mechanical ventilation in patients who were extubated 11 days
      • PubMed32227758The New England journal of medicineN Engl J Med20200330Reference - N Engl J Med 2020 Mar 30 early online
    • Study Summary
      88.1% mortality reported in hospitalized patients in New York receiving mechanical ventilation
      Details
      Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorders88.1% mortality reported in hospitalized patients in New York receiving mechanical ventilation (JAMA 2020 Apr 22 early online)04/27/2020 11:31:47 AMstudySummary
      • Case Series based on cohort study
      • 5,700 patients (median age 63 years) with COVID-19 admitted to hospitals in New York, United States, between March 1 and April 4, 2020, were evaluated
      • 46% were discharged from hospital or died (definite outcomes), and 54% remained hospitalized at end of study
      • among patients with definite outcomes
        • median length of stay 4.1 days
        • 14.2% were treated in intensive care unit (ICU)
        • 12.2% received mechanical ventilation
        • 3.2% had renal replacement therapy
        • 2.2% were readmitted
        • 21% died
      • mortality 88.1% among patients requiring mechanical ventilation
        • 76.4% in patients aged 18-65 years
        • 97.2% in patients > 65 years old
      • mortality 11.7% among patients not requiring mechanical ventilation
        • 19.8% in patients aged 18-65 years
        • 26.6% in patients > 65 years old
      • PubMed32320003JAMAJAMA20200422Reference - JAMA 2020 Apr 22 early online
  • Study Summary
    26% mortality reported in adults ≥ 21 years old with confirmed COVID-19 admitted to COVID-only ICUs in Lombardy, Italy
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorders26% mortality reported in adults ≥ 21 years old with confirmed COVID-19 admitted to COVID-only intensive care units in Lombardy, Italy (JAMA 2020 Apr 6 early online)04/10/2020 12:07:46 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 1,591 children and adults aged 14-91 years (median age 63 years, 82% male) with laboratory-confirmed COVID-19 consecutively admitted to 72 COVID-only ICUs in Lombardy, Italy, between February 20 and March 18, 2020, were assessed until March 25, 2020
      • 1,043 had data on comorbidities
      • 1,300 had data on respiratory support
      • 1,581 had data on ICU outcome
    • 0.2% were ≤ 20 years old, 13% were aged 21-50 years, 64% were aged 51-70 years, and 22.8% were ≥ 71 years old
    • 68% had ≥ 1 comorbidity, including
      • hypertension in 49%
      • cardiovascular disease in 21%
      • hypercholesterolemia in 18%
      • type 2 diabetes in 17%
      • malignancy in 8%
      • chronic obstructive pulmonary disease in 4%
      • chronic kidney disease in 3%
      • chronic liver disease in 3%
    • 32% had no comorbidities
    • 100% needed respiratory support
      • invasive mechanical ventilation in 88%
      • noninvasive ventilation in 11%
      • oxygen mask in 1%
      • median positive end-expiratory pressure (PEEP) was 14 cm H2O
      • median fraction of inspired oxygen (FiO2) needed was 70%
        • FiO2 ≥ 50% needed in 89%
        • FiO2 100% needed in 12%
      • median arterial partial pressure of oxygen (PaO2)/FiO2 ratio was 160
    • ICU outcomes
      • overall mortality 26%
        • mortality for ages 21-40 years 7%
        • mortality for ages 41-50 years 11%
        • mortality for ages 51-60 years 15%
        • mortality for ages 61-70 years 29%
        • mortality for ages 71-80 years 40%
        • mortality for ages ≥ 81 years 55%
      • 58% remained in ICU
      • 16% were discharged
      • median length of stay in patients discharged from ICU 8 days
    • comparing patients ≤ 63 years old vs. ≥ 64 years old
      • ICU mortality 15% vs. 36% (p < 0.001)
      • median PEEP 14 cm H2O vs. 14 cm H2O (not significant)
      • median FiO2 60% vs. 70% (p = 0.006)
      • median PaO2/FiO2 163.5 vs. 156 (p = 0.02)
    • comparing patients with history of hypertension vs. no hypertension
      • median age 66 years vs. 62 years (p < 0.001)
      • ICU mortality 38% vs. 22% (no p value reported)
      • median PaO2/FiO2 146 vs. 173 (p = 0.005)
      • median FiO2 70% vs. 60% (p = 0.05)
    • PubMed32250385JAMAJAMA20200406Reference - JAMA 2020 Apr 6 early online, editorial can be found in JAMA 2020 Apr 6 early online
  • Study Summary
    0.9% case fatality proportion reported in patients with confirmed COVID-19 in the Republic of Korea
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disorders0.9% case fatality proportion reported in patients with confirmed COVID-19 in the Republic of Korea (Osong Public Health Res Perspect 2020 Apr)04/27/2020 11:32:49 AMstudySummary
    • Cohort Study based on cohort study
    • 7,755 patients with confirmed COVID-19 in the Republic of Korea's National Notifiable Disease Surveillance System as of March 12, 2020, were evaluated
    • 66 patients died (case fatality proportion 0.9%)
      • case fatality proportion by age
        • 0% for ages 0-29 years
        • 0.1% for ages 30-49 years
        • 0.4% for ages 50-59 years
        • 1.5% for ages 60-69 years
        • 5% for ages 70-79 years
        • 8.5% for ages ≥ 80 years
      • case fatality proportion by sex
        • 0.5% for females
        • 1.2% for males
    • coexisting medical conditions among patients who died included
      • hypertension in 47.6%
      • diabetes mellitus in 36.5%
      • neurodegenerative disorder in 25.4%
      • pulmonary disease in 17.5%
      • heart disease in 15.9%
      • cancer in 11.1%
      • cerebrovascular disease in 7.9%
      • kidney disease in 7.9%
    • PubMed32257774Osong public health and research perspectivesOsong Public Health Res Perspect2020040111285-9085Reference - Osong Public Health Res Perspect 2020 Apr;11(2):85full-text

Factors associated with severe disease and mortality

  • factors that may be associated with higher risk for severe illness and complications include1
    • age ≥ 65 years
    • residence in long-term care facilities
    • underlying conditions including
      • chronic lung disease or moderate-severe asthma
      • serious heart conditions
      • severe obesity (body mass index ≥ 40)
      • diabetes
      • chronic kidney disease requiring dialysis
      • liver disease
      • immunocompromising conditions including
        • cancer treatment
        • smoking
        • bone marrow or organ transplantation
        • immune deficiency disorders
        • poorly controlled HIV or AIDS
        • prolonged use of corticosteroids or other immunosuppressive drugs
  • Study Summary
    older age and preexisting cardiovascular disease associated with increased mortality in patients hospitalized with COVID-19
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersolder age and preexisting cardiovascular disease associated with increased mortality in patients hospitalized with COVID-19 (Intensive Care Med 2020 Mar 3 early online)03/05/2020 01:34:23 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 150 patients with COVID-19 at 2 hospitals in Wuhan, China, were evaluated
    • 68 patients died, with cause of death
      • respiratory failure in 53%
      • respiratory failure plus circulatory failure in 33%
      • circulatory failure in 7%
      • unknown cause in 7%
    • comparing patients who died vs. patients discharged
      • median age 67 years vs. 50 years (p < 0.001)
      • preexisting cardiovascular disease in 19% vs. 0% (p < 0.001)
      • clinical factors
        • dyspnea in 87% vs. 62% (p = 0.001)
        • respiratory failure in 85% vs. 16% (p < 0.001)
        • acute respiratory distress syndrome in 81% vs. 9% (p < 0.001)
        • acute kidney injury in 31% vs. 2% (p < 0.001)
        • secondary infection in 16% vs. 1% (p = 0.002)
      • laboratory findings
        • mean white blood cell count 10.6 × 109 cells/L vs. 6.8 × 109 cells/L (p < 0.001)
        • mean lymphocyte count 0.6 × 109 cells/L vs. 1.4 × 109 cells/L (p < 0.001)
        • mean platelet count 174 × 109 cells/L vs. 222 × 109 cells/L (p < 0.001)
        • mean albumin 28.8 g/L vs. 32.7 g/L (p < 0.001)
        • mean blood urea nitrogen 8.7 mmol/L vs. 5.1 mmol/L (p < 0.001)
        • mean cardiac troponin 30.3 pg/mL vs. 3.5 pg/mL (p < 0.001)
        • mean C-reactive protein 126.6 mg/L vs. 34.1 mg/L (p < 0.001)
        • mean interleukin-6 11.4 ng/mL vs. 6.8 ng/mL (p < 0.001)
        • mean total bilirubin 18.1 mcmol/L vs. 12.8 mcmol/L (p = 0.001)
        • mean creatinine 91.2 mmol/L vs. 72.1 mmol/L (p = 0.02)
    • PubMed32125452Intensive care medicineIntensive Care Med20200303Reference - Intensive Care Med 2020 Mar 3 early online
  • Study Summary
    older age, higher Sequential Organ Failure Assessment (SOFA) score, and d-dimer > 1 mcg/mL associated with increased in-hospital mortality in adults with COVID-19
    Details
    Critical_Care Infectious_Diseases Internal_Medicine Pulmonary_Disordersolder age, higher Sequential Organ Failure Assessment score, and d-dimer > 1 mcg/mL associated with increased in-hospital mortality in adults with COVID-19 (Lancet 2020 Mar 11 early online)03/18/2020 01:22:56 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 191 adults aged 18-87 years (median age 56 years, 62% men) with laboratory-confirmed COVID-19 admitted to 2 hospitals in Wuhan, China, and who died (28%) or were discharged by January 31, 2020, were assessed
      • most common symptoms on admission included fever (94%), cough (79%), sputum (23%), fatigue (23%), and myalgia (15%)
      • 48% had comorbidity
    • 95% received antibiotics, and 21% received antivirals (lopinavir/ritonavir)
    • increased in-hospital mortality associated with
      • older age (adjusted odds ratio [OR] 1.1 per year increase, 95% CI 1.03-1.17)
      • higher SOFA score (adjusted OR 5.65, 95% CI 2.61-12.23)
      • d-dimer > 1 mcg/mL on admission (adjusted OR 18.42, 95% CI 2.64-128.55) compared to ≤ 0.5 mcg/mL
    • comparing nonsurvivors vs. survivors (p < 0.0001 for each unless otherwise indicated)
      • median age 69 years vs. 52 years
      • SOFA score 4.5 points vs. 1 point
      • comorbidities
        • hypertension in 48% vs. 23% (p = 0.0008)
        • diabetes in 31% vs. 14% (p = 0.0051)
        • coronary heart disease in 24% vs. 1%
        • chronic obstructive lung disease in 7% vs. 1% (p = 0.047)
        • chronic kidney disease in 4% vs. 0% (p = 0.024)
      • laboratory findings
        • d-dimer ≥ 1 mcg/mL in 81% vs. 24%
        • median white blood cell count 9.8 × 109/L vs. 5.2 × 109/L
        • lymphocyte < 0.8 × 109/L in 76% vs. 26%
        • anemia in 26% vs. 11% (p = 0.0094)
        • platelet count < 100 × 109/L in 20% vs. 1%
        • high-sensitivity cardiac troponin I ≥ 28 pg/mL in 46% vs. 1%
      • thoracic imaging
        • consolidation in 74% vs. 53% (p = 0.0065)
        • ground glass opacity in 81% vs. 67% (p = 0.049)
        • bilateral pulmonary infiltration in 83% vs. 72% (p = 0.09)
      • outcomes
        • sepsis in 100% vs. 42%
        • respiratory failure in 98% vs. 36%
        • acute respiratory distress syndrome in 93% vs. 7%
        • septic shock in 70% vs. 0%
        • acute cardiac injury in 59% vs. 1%
        • acute kidney injury in 50% vs. 1%
        • heart failure in 52% vs. 12%
        • secondary infection in 50% vs. 1%
        • coagulopathy in 50% vs. 7%
      • treatments
        • invasive mechanical ventilation in 57% vs. 1%
        • noninvasive mechanical ventilation in 44% vs. 1%
        • extracorporeal membrane oxygenation in 6% vs. 0% (p = 0.0054)
        • renal replacement therapy in 19% vs. 0%
        • intravenous immunoglobulin in 67% vs. 7%
        • corticosteroid in 48% vs. 23% (p = 0.0005)
    • median time from illness onset to
      • discharge 22 days
      • death 18.5 days
      • invasive mechanical ventilation 14.5 days
      • stop viral shedding in survivors 20 days (range 8-37 days)
    • PubMed32171076Lancet (London, England)Lancet20200311Reference - Lancet 2020 Mar 11 early online
  • Study Summary
    age ≥ 65 years and elevated lactate dehydrogenase associated with severe disease and mortality in patients hospitalized with COVID-19 in China
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersage ≥ 65 years and elevated lactate dehydrogenase associated with severe disease and mortality in patients hospitalized with COVID-19 in China (J Allergy Clin Immunol 2020 Apr 12 early online)04/27/2020 11:34:09 AMstudySummary
    • Cohort Study based on cohort study
    • 548 adults (median age 60 years) with COVID-19 admitted to Tongji hospital in Wuhan, China, between January 26 and February 5, 2020, had clinical and laboratory records evaluated and were followed until March 3, 2020
    • 269 patients (49.1%) classified as severe at admission based on American Thoracic Society/Infectious Diseases Society of America definition for severe community-acquired pneumonia
    • factors associated with severe disease at admission in multivariable analysis
      • lactate dehydrogenase > 445 units/L (odds ratio [OR] 4.4, 95% CI 2.6-7.6)
      • age ≥ 65 years (OR 2.2, 95% CI 1.5-3.5)
      • d-dimer > 1 mg/L (OR 2.2, 95% CI 1.4-3.3)
      • hypertension (OR 2, 95% CI 1.3-3.2)
    • during mean 32 days of follow-up
      • 32.5% of patients with severe disease died, and 31.7% were discharged
      • 1.1% of patients with nonsevere disease died, and 72.9% were discharged
    • factors associated with mortality in patients with severe disease in multivariable analysis
      • administration of high-dose corticosteroids (adjusted hazard ratio [HR] 3.5, 95% CI 1.79-6.86)
      • cardiac injury during hospitalization (adjusted HR 2.92, 95% CI 1.8-4.76)
      • blood leukocyte count > 10 cells/mm3 at admission (adjusted HR 2.04, 95% CI 1.26-3.31)
      • lactate dehydrogenase > 445 units/L at admission (adjusted HR 2, 95% CI 1.21-3.3)
      • hyperglycemia during hospitalization (adjusted HR 1.77, 95% CI 1.11-2.84)
      • male sex (adjusted HR 1.72, 95% CI 1.05-2.82)
      • age ≥ 65 years (adjusted HR 1.72, 95% CI 1.09-2.73)
    • PubMed32294485The Journal of allergy and clinical immunologyJ Allergy Clin Immunol20200412Reference - J Allergy Clin Immunol 2020 Apr 12 early onlinefull-text
  • Study Summary
    history of smoking and older age associated with deterioration in hospitalized patients with COVID-19 pneumonia in China
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordershistory of smoking and older age associated with deterioration in hospitalized patients with COVID-19 pneumonia in China (Chin Med J (Engl) 2020 Feb 28 early online)03/05/2020 01:35:49 PMstudySummary
    • Cohort Study based on retrospective cohort study
    • 78 patients (median age 38 years) with COVID-19 pneumonia hospitalized for > 2 weeks in 3 hospitals in Wuhan, China, between December 30, 2019 and January 15, 2020, were evaluated
    • deterioration in 11 patients (14.1%) after 2 weeks of hospitalization
    • factors associated with deterioration in multivariate analysis
      • history of smoking (odds ratio [OR] 14.3, 95% CI 1.6-25)
      • C-reactive protein > 8.2 mg/L (OR 10.5, 95% CI 1.2-34.7)
      • maximum body temperature at admission ≥ 37.3 degrees C (99.14 degrees F) (OR 9, 95% CI 1.04-78.1)
      • respiratory failure (OR 8.8, 95% CI 1.9-40)
      • age ≥ 60 years (OR 8.5, 95% CI 1.6-44.9)
      • albumin < 40 g/L (OR 7.4, 95% CI 1.1-50)
    • PubMed32118640Chinese medical journalChin Med J (Engl)20200228Reference - Chin Med J (Engl) 2020 Feb 28 early online
  • Study Summary
    higher D-dimer level, fibrin degradation product, and prolonged prothrombin time (PT) on admission associated with decreased survival in patients hospitalized for COVID-19 pneumonia
    Details
    Critical_Care Hematologic_Disorders Hospital_Medicine Infectious_Diseases Internal_Medicinehigher D-dimer level, fibrin degradation product, and prolonged prothrombin time on admission associated with decreased survival in patients hospitalized for COVID-19 pneumonia (J Thromb Haemost 2020 Apr)04/27/2020 11:35:12 AMstudySummary
    • Cohort Study based on retrospective cohort study
    • 183 patients (mean age at disease onset 54 years) with confirmed COVID-19 pneumonia presenting to Tongji hospital in Wuhan, China, between January 1, 2020 and February 3, 2020, had their clinical and laboratory records evaluated
    • 41% had chronic diseases such as cardiovascular and cerebrovascular disease, respiratory system disease, malignancy, or chronic liver or kidney disease
    • all patients received antiviral and supportive therapies
    • by February 13, 2020, 11.5% had died, 42.6% were discharged, and 45.9% remained in hospital in stable condition; patients who died were significantly older (mean age 64 years vs. 52 years among survivors, p < 0.001)
    • comparing nonsurvivors vs. survivors
      • baseline patient characteristics
        • D-dimer level 2.12 mg/L vs. 0.61 mg/L (p < 0.001)
        • fibrin degradation product 7.6 mg/L vs. 4 mg/L (p < 0.001)
        • median PT 15.5 seconds vs. 13.6 seconds (p < 0.001)
        • median activated partial thromboplastin time 44.8 seconds vs. 41.2 seconds (p = 0.096)
        • fibrinogen 5.16 g/L vs. 4.51 g/L (not significant)
        • antithrombin activity 84% vs. 91% (p = 0.096)
      • development of overt disseminated intravascular coagulation (DIC) as defined by International Society on Thrombosis and Haemostasis diagnostic criteria (≥ 5 points) in 71.4% vs. 0.6%; median time to DIC 4 days
    • factors associated with death at 10 days and 14 days after hospitalization
      • elevated D-dimer levels, prolonged PT, or elevated fibrinogen degradation products (p < 0.05)
      • reduced fibrinogen levels and antithrombin activity (p < 0.05)
    • PubMed32073213Journal of thrombosis and haemostasis : JTHJ Thromb Haemost20200401184844-847844Reference - J Thromb Haemost 2020 Apr;18(4):844full-text, commentary can be found in J Thromb Haemost 2020 Apr;18(4):786
  • Study Summary
    male sex, presence of comorbidities, shortness of breath, and creatinine > 105 mcmol/L (1.19 mg/dL) associated with increased mortality in patients ≥ 65 years old hospitalized with COVID-19
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_Disordersmale sex, presence of comorbidities, shortness of breath, and creatinine > 105 mcmol/L (1.19 mg/dL) associated with increased mortality in patients ≥ 65 years old hospitalized with COVID-19 (J Gerontol A Biol Sci Med Sci 2020 Apr 11 early online)04/27/2020 11:36:42 AMstudySummary
    • Cohort Study based on retrospective cohort study
    • 203 adults (median age 54 years) with COVID-19 admitted to 1 hospital in Wuhan, China, from January 1 to February 10, 2020, were evaluated
    • 55 patients were ≥ 65 years old
    • mortality 34.5% in patients ≥ 65 years old vs. 4.7% in patients < 65 years old (p < 0.001)
    • factors associated with mortality in patients ≥ 65 years old in multivariate analysis
      • presence of any comorbidities (odds ratio [OR] 16.1, 95% CI 1.9-133.8)
      • male sex (OR 13.8, 95% CI 1.4-136.1)
      • shortness of breath (OR 12.9, 95% CI 1.8-94.4)
      • creatinine > 105 mcmol/L (1.19 mg/dL) (OR 4.8, 95% CI 1.2-17)
    • Reference - J Gerontol A Biol Sci Med Sci 2020 Apr 11 early online
  • Study Summary
    CALL risk score may help predict risk of progression to severe disease in adults hospitalized with COVID-19
    DynaMed Level2
    Details
    Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersCALL risk score may help predict risk of progression to severe disease in adults hospitalized with COVID-19 (Clin Infect Dis 2020 Apr 9 early online)04/27/2020 11:37:56 AMstudySummary
    • Prediction Rule based on prognostic cohort study without independent validation
    • 208 adults (mean age 44 years) hospitalized with COVID-19 in China from January 2020 to February 2020 were followed until March 2020
      • diagnosis of COVID-19 based on World Health Organization interim guidance for diagnosis and National Health Commission of China guidance for coronavirus disease 2019
      • 21.6% had ≥ 1 comorbidity, including hypertension, diabetes, cardiovascular disease, liver disease, asthma, chronic lung disease, HIV infection, and malignancy for ≥ 6 months
      • patients presenting with severe COVID-19 were excluded
    • progression to severe COVID-19 defined as either of
      • ≥ 1 of the following: respiratory rate ≥ 30 breaths/minute, resting oxygen saturation ≤ 93%, PaO2/FiO2 ≤ 300 mm Hg, or mechanical ventilation
      • worsening of lung computed tomography findings
    • progression to severe disease in 19.2%
    • CALL score developed using 4 factors (Comorbidity, Age, Lymphocyte count, and Lactate dehydrogenase) significantly associated with progression to severe disease (range 4-13 points)
      • presence of comorbidity
        • no comorbidity = 1 point
        • ≥ 1 comorbidity = 4 points
      • age
        • ≤ 60 years old = 1 point
        • ≥ 60 years old = 3 points
      • lymphocyte count
        • > 1 × 109cells/L = 1 point
        • ≤ 1 × 109cells /L (lymphopenia) = 3 points
      • lactate dehydrogenase
        • ≤ 250 units/L = 1 point
        • 250-500 units/L = 2 points
        • > 500 units/L = 3 points
    • for prediction of progression to severe disease, CALL score with cutoff > 6 points had
      • sensitivity 95%
      • specificity 78%
      • positive predictive values 50.7%
      • negative predictive values 98.5%
    • additional nomogram for prediction of progression risk can be found in full text
    • PubMed32271369Clinical infectious diseases : an official publication of the Infectious Diseases Society of AmericaClin Infect Dis20200409Reference - Clin Infect Dis 2020 Apr 9 early online

Infection Control

Prevention and Screening

  • CLINICIANS' PRACTICE POINT

    Measures to secure the safety of all, including the general public, patients, and healthcare providers, is a fluid process. Decisions regarding home quarantine, supervised quarantine, voluntary furlough, and mandatory furlough must be based upon the most current information for a given area. Healthcare Systems should meet regularly with representation from administration, healthcare providers, infection control, environmental services, laboratory, security, human resources, information systems, etc., to review their situation. Agenda items may include local disease activity (including number of hospitalized patients), surge capacity, staffing issues (including furlough decisions), supply issues, and current recommendations from public health organizations. Open communication and ability to adjust to rapidly changing circumstances is paramount.

Recommendations from Professional Organizations

World Health Organization (WHO)

  • WHO interim guidance on infection prevention and control when COVID-19 is suspected
    • ensuring triage, early recognition, and source control
      • recognize and place patients in separate area from other patients during clinical triage
        • encourage healthcare workers to have high level of clinical suspicion
        • establish triage station at entrance of healthcare facility
        • use screening questionnaire
        • post signage in public areas reminding symptomatic patients to alert healthcare workers
      • promote hand and respiratory hygiene
    • standard precautions for all patients at all times
      • hand and respiratory hygiene
        • offer medical mask for suspected COVID-19
        • cover nose and mouth during coughing or sneezing with tissue or flexed elbow
        • wash hands after contact with respiratory secretions
      • use personal protective equipment (PPE)
      • clean and disinfect environment
      • practice safe waste management
      • sterilize patient-care equipment, linen, and food utensils
    • additional precautions for suspected COVID-19
      • contact and droplet precautions
        • apply to all patients, family members, visitors, and healthcare workers in addition to standard precautions
        • continue until patient is asymptomatic
        • place patients in adequately ventilated single rooms (air flow ≥ 160 L/second/patient for naturally ventilated general ward rooms)
        • group patients suspected of COVID-19 together if single room unavailable, with patient beds ≥ 1 meter apart
        • group healthcare workers to exclusively care for suspected COVID-19 cases if possible
        • wear the following PPE
          • medical mask
          • eye/face protection, such as goggles or face shield
          • clean, nonsterile, long-sleeved gown
          • gloves
        • appropriately doff and dispose of all PPE after patient care and practice hand hygiene, use a new set of PPE when caring for different patient
        • do not touch eyes, nose, or mouth with potentially contaminated hands
        • use either single-use disposable equipment or dedicated equipment (such as with stethoscopes, blood pressure cuffs, and thermometers)
        • for shared equipment, clean and disinfect between each patient
        • do not move or transport patients out of room or area unless medically necessary
          • use designated portable diagnostic equipment, such as portable x-ray equipment
          • use predetermined transport routes if transportation required, and apply medical mask to patient
          • during transport, wear proper PPE and perform hand hygiene for healthcare workers
          • notify receiving area of necessary precautions as soon as possible before patient's arrival
        • clean and disinfect patient-contact surfaces routinely
        • limit number of healthcare workers, family members, and visitors in contact with patient with suspected COVID-19
        • maintain record of all persons entering patient's room
      • airborne precautions for aerosol-generating procedures
        • examples of aerosol-generating procedures include tracheal intubation, noninvasive ventilation, tracheotomy, cardiopulmonary resuscitation, manual ventilation before intubation, and bronchoscopy
        • when performing aerosol-generating procedures
          • use particulate respirator at least as protective as a NIOSH-certified N95, EU FFP2, or equivalent
          • always perform seal check when putting on disposable particulate respirator, and note that facial hair may prevent proper fit
          • wear eye protection, such as goggles or face shield
          • wear clean, nonsterile, long-sleeved gown and gloves; use waterproof apron for procedures with expected high fluid volumes if gowns are not fluid resistant
          • perform procedures in adequately ventilated room
            • natural ventilation with ≥ 160 L/second/patient air flow, or
            • negative pressure rooms with ≥ 12 air changes per hour (ACH) with controlled direction of air flow when using mechanical ventilation
          • limit number of persons present in the room
    • administrative controls
      • establish sustainable infection prevention and control infrastructures and activities
      • educate patient's caregivers
      • establish policies on early recognition of acute respiratory infection potentially due to COVID-19
      • obtain access to prompt laboratory testing for identification of etiologic agent
      • prevent overcrowding, especially in emergency department
      • provide dedicated waiting areas for symptomatic patients
      • appropriately isolate hospitalized patients
      • ensure adequate supplies of PPE
      • establish policies and procedures to ensure adherence for all facets of healthcare provisions, with emphasis on
        • training healthcare workers
        • promoting adequate patient-to-staff ratio
        • establishing surveillance process for acute respiratory infections potentially due to COVID-19 among healthcare workers
        • stressing importance of seeking medical care
        • monitoring compliance and providing mechanisms for improvements as needed
    • collection and handling of laboratory specimens from patient with suspected COVID-19
      • all specimens should be considered as potentially infectious
      • use standard precautions to minimize potential pathogen exposure
      • healthcare workers collecting specimens should
        • use appropriate PPE including eye protection, medical mask, long-sleeved gown, and gloves
        • wear particulate respirator at least as protective as a NIOSH-certified N95, EU FFP2, or equivalent during aerosol generating procedures
      • train all personnel who transport specimens on safe-handling practices and spill decontamination procedures
      • place specimens for transport in leak-proof specimen bags (secondary container) with separate sealable pocket, with label on primary specimen container, and with clearly written laboratory request form
      • adhere to appropriate biosafety practices and transport requirements for healthcare facility laboratories
      • deliver all specimens by hand whenever possible; do not use pneumatic-tube systems
      • document patients full name, date of birth, and potential concern of suspected COVID-19 clearly on accompanying laboratory request form, and notify laboratory as soon as possible of specimen being transported
    • basic principles of infection prevention and control should also be applied in outpatient care settings, including
      • triage and early recognition
      • emphasize hand and respiratory hygiene
      • offer medical masks to patients with respiratory symptoms
      • use appropriate contact and droplet precautions for all suspected cases
      • prioritize care for symptomatic patients
      • ensure separate waiting area for symptomatic patients
      • educate patients and family about early recognition, precautions to use, and which healthcare facility to refer to
    • Reference - WHO Infection prevention and control during health care when novel coronavirus (nCoV) infection is suspected (WHO 2020 Mar 19)

United States Centers for Disease Control and Prevention (CDC)

Healthcare settings
  • CDC interim recommendations for infection prevention and control for patients with suspected or confirmed COVID-19 in healthcare settings
    • minimize chance for exposures
      • implement universal source control
        • everyone entering facility should wear cloth face covering regardless of symptoms
          • patients and visitors
            • patients and visitors should wear cloth face covering upon arrival to facility or be offered a face mask as supplies allow
            • face covering not needed for children aged < 2 years, persons with trouble breathing, and persons who are unconscious, incapacitated, or unable to remove mask
            • patients may remove face covering in their room, but should wear them when leaving room or when others enter, such as visitors or healthcare personnel
          • healthcare personnel
            • healthcare personnel should wear medical face masks at all times in healthcare facilities
            • face masks preferred over cloth face coverings, as they offer both source control and prevention against infection
            • healthcare personnel who do not require PPE (such as clerical personnel) may wear cloth face covering
            • cloth face covering should not replace respiratory or face mask if more than source control is necessary
        • actively screen everyone for fever and other symptoms before entry into healthcare facility
        • as community transmission intensifies within a region, consider forgoing contact tracing for exposures in healthcare facility in favor of universal source control and screening for fever and other symptoms before every shift
      • before arrival
        • when scheduling patients for routine medical care, instruct patients to call ahead and discuss need to reschedule if they develop symptoms of a respiratory infection on the day they are scheduled to be seen
        • when scheduling appointments for patients requesting evaluation for respiratory infection, use triage protocols to determine if appointment is necessary or if the patient can be managed at home
        • instruct patients with symptoms of respiratory infection coming in for an appointment to wear face mask upon entry and follow triage procedures
        • for patients arriving via transport by emergency medical services, alert receiving emergency department or healthcare facility to prepare for patient
      • upon arrival and during visit
        • consider limiting points of entry to the facility
        • take steps to ensure respiratory hygiene
          • post visual alerts at entrances and strategic places to provide instructions about hand hygiene, respiratory hygiene, and cough etiquette
          • provide supplies for respiratory hygiene and cough etiquette including 60%-95% alcohol-based hand sanitizer, tissues, and no-touch receptacles for disposal at entrances, waiting rooms, and patient check in areas
          • install physical barriers such as glass or plastic windows at reception areas to limit close contact between triage personnel and potentially infectious patients
          • consider creating triage stations outside the facility to screen patients prior to entry
        • ensure rapid triage and isolation of patients with suspected COVID-19
          • prioritize patients with respiratory symptoms
          • supply patients with symptoms of respiratory infection with face masks and tissues (putting a face mask over the mouth and nose of a symptomatic patient can help to prevent transmission to others)
          • ask all patients about
            • presence of respiratory symptoms
            • history of travel to areas experiencing transmission of COVID-19
            • contact with other persons with possible COVID-19
          • isolate the patient in an exam room with the door closed
          • if an examination room is not readily available
            • identify a separate, well-ventilated space that allows waiting patients to be separated by ≥ 6 feet, with access to respiratory hygiene supplies
            • in some settings, patients might opt to wait outside the healthcare facility or in a personal vehicle until they are contacted by mobile phone when it is their turn to be evaluated
          • monitor all admitted patients for new fevers and respiratory illnesses, and place any patient with unexplained fever or respiratory symptoms on transmission-based precautions for evaluation
        • during periods of community transmission consider
          • alternatives to face-to-face triage and visits
          • designating an area at the facility or location in the area to be a “respiratory virus evaluation center” where patients with fever or respiratory symptoms can seek evaluation and care
          • cancelling group healthcare activities
          • postponing elective procedures, surgeries, and nonurgent outpatient visits
    • adherence to standard, contact, and airborne precautions
      • hand hygiene
        • healthcare personnel should perform hand hygiene before and after all patient contact, contact with potentially infectious material, and before donning or removing PPE
        • hand hygiene includes use of 60%-95% alcohol-based hand sanitizers or soap and water for ≥ 20 seconds
        • hand hygiene supplies should be readily available in every care location
      • PPE includes
        • gloves
        • gowns
        • eye protection
        • N95 respirator or respirators offering higher level of protection (preferred)
          • face masks are an acceptable alternative when the supply of respirators cannot meet demand
          • available respirators should be prioritized for procedures that are likely to generate respiratory aerosols and care of patients with other infections for which respiratory protection strongly indicated (such as measles, varicella, or tuberculosis)
          • if using reusable respirators, clean and disinfect prior to reuse
      • specimen collection
        • limit number of healthcare personnel present during procedure; visitors should not be present
        • healthcare providers in room should wear N95 or higher respirators (or face masks if respirators unavailable), eye protection, gloves, and gowns
        • nasopharyngeal swabs can be collected in normal exam room with door closed
        • aerosol-generating procedures should take place in AIIR
        • clean and disinfect surfaces promptly after completion
    • patient placement
      • evaluate need for hospitalization, as home care is preferable if hospitalization is not medically necessary and the individual’s situation allows
      • consider designating entire units within the facility to care for known or suspected COVID-19 patients
      • patients with known or suspected COVID-19 should be cared for in a single-person room with the door closed, with Airborne Infection Isolation Rooms (AIIRs) reserved for patients undergoing aerosol-generating procedures
      • limit transport or movement of patient outside of the room and have patients wear face mask to contain secretions
      • to the extent possible, house patients in the same room for the duration of their stay
      • personnel entering room should wear proper personal protective equipment (PPE)
      • whenever possible, perform procedures/tests in the patient’s room
      • after discharge or transfer
        • healthcare personnel (including environmental services personnel) should refrain from entering the vacated room until sufficient time has elapsed for enough air changes to remove potentially infectious particles
        • after time has elapse, room should undergo appropriate cleaning and surface disinfection before returned to routine use
    • manage visitor access and movement within facility
      • establish procedures for monitoring, managing, and training visitors
      • limit visitors of patients with known or suspected COVID-19
      • all visitors should be scheduled and controlled
        • actively screen visitors for fever and COVID-19 symptoms prior to entry, and deny entry if symptoms present
        • evaluate risk to health of visitor
        • instruct visitors to wear face mask or cloth face covering while in facility
        • provide instruction on hand hygiene, limiting surfaces touched, and use of PPE prior to entering patient room
        • prevent visitors from access during aerosol-generating procedures
        • instruct visitors to limit movement within facility
      • ensure visitors follow respiratory hygiene and cough etiquette while in facility
    • consider designing and installing engineering controls to reduce or eliminate exposures
    • monitor and manage ill healthcare personnel in consultation with public health authorities
    • train and educate healthcare personnel
    • implement environmental infection control
      • use dedicated medical equipment for patient care
      • clean and disinfect all nondedicated, nondisposable equipment to manufacturer's instructions and facility policies
      • ensure environmental cleaning and disinfection procedures are followed
      • Environmental Protection Agency (EPA)-approved products for emerging viral pathogens are recommended for routine cleaning and disinfection procedures
      • manage laundry, food service, and medical waste in accordance with routine procedures
    • establish reporting within healthcare facilities and to public health authorities
      • implement mechanisms and policies to alert key facility staff
      • communicate and collaborate with public health authorities
    • Reference - CDC interim infection prevention and control recommendations for patients with suspected or confirmed coronavirus disease 2019 (COVID-19) in healthcare settings (CDC 2020 Apr 13)
  • duration of transmission-based precautions for persons under investigation and patients with confirmed COVID-19
    • discontinuation of transmission-based precautions for patients with COVID-19 may be made using test-based or non-test-based strategy
      • test-based strategy consists of both
        • clinical recovery (resolution of fever without use of fever-reducing medications and improvement in respiratory symptoms)
        • negative result on FDA Emergency Use Authorized COVID-19 molecular assay for detection of SARS-CoV-2 from ≥ 2 consecutive nasopharyngeal swabs taken ≥ 24 hours apart
      • non-test-based strategy consists of both
        • ≥ 3 days since clinical recovery (resolution of fever without use of fever-reducing medications and improvement in respiratory symptoms)
        • ≥ 7 days since first appearance of symptoms
      • test-based strategy preferred for patients with longer duration of virus detection and shedding or close contact with persons at high risk of severe disease, such as patients who are
        • hospitalized
        • severely immunocompromised
        • being transferred to long-term care or assisted living facility
    • discontinuation of transmission-based precautions for patients suspected of having COVID-19
      • decision based on clinical judgement and suspicion of infection
      • negative results from ≥ 1 FDA Emergency Use Authorized COVID-19 molecular assay for detection of SARS-CoV-2 supports discontinuation
      • if higher level of suspicion for COVID-19, consider maintaining precautions and performing second test
      • non-test-based strategy may be used if patient was never tested
    • disposition of patients with COVID-19
      • discharge patients when clinically indicated
      • if discharged home
        • maintain isolation at home if patient returns home prior to discontinuation of transmission-based precautions
        • make decision to discharge home in conjunction with clinical care team and public health departments
        • consider suitability for and patient ability to adhere to home isolation recommendations
      • if discharged to long-term care or assisted living facility, recommendations vary by need for transmission-based precautions
        • if transmission-based precautions still required, patient should go to facility with ability to adhere to infection prevention and control recommendations
        • if transmission-based precautions discontinued, but patient has persistent symptoms, patient should be placed in single room, be restricted to room, and wear face mask during care activities for 14 days after illness onset or until all symptoms resolve, whichever is longer
        • if transmission-based precautions discontinued and symptoms have resolved, no further restrictions required
    • Reference - CDC interim considerations for discontinuation of transmission-based precautions and disposition of hospitalized patients with COVID-19 (CDC 2020 Mar 23)
  • additional CDC setting-specific interim guidance
    • interim United States guidance for risk assessment and public health management of healthcare personnel with potential exposure in a healthcare setting to patients with coronavirus disease (COVID-19) (CDC 2020 Mar 7)
    • interim guidance for emergency medical services (EMS) systems and 911 public safety answering points (PSAPs) for COVID-19 in United states (CDC 2020 Mar 10)
    • interim guidance for pediatric healthcare providers (CDC 2020 Apr 3)
    • interim infection prevention and control recommendations for patients of coronavirus disease (COVID-19) in inpatient obstetric healthcare settings (CDC 2020 Feb 18)
  • CDC interim guidance for healthcare facilities
    • interim guidance containing criteria for return to work for healthcare personnel with confirmed or suspected COVID-19 (CDC 2020 Mar 16)
    • steps healthcare facilities can take now to prepare for COVID-19 (CDC 2020 Mar 20)
    • sequence for putting on personal protective equipment (CDC 2020 PDF)
    • interim guidance on preparing for COVID-19 in long-term care facilities and nursing homes can be found at CDC 2020 Mar 21
    • interim additional guidance for infection prevention and control recommendations for patients with suspected or confirmed COVID-19 in outpatient dialysis facilities (CDC 2020 Mar 30)
  • CDC interim guidance for health departments
Community settings
  • CDC general community guidance1
    • avoiding exposure to virus is best way to prevent illness
    • clean hands often
      • wash hands with soap and water for ≥ 20 seconds
      • if soap and water are not available, use hand sanitizer with ≥ 60% alcohol
      • avoid touching eyes, nose, and mouth with unwashed hands
    • avoid close contact with people who are sick
    • if COVID-19 is spreading in a community, create distance between residents
    • stay home if sick except to get medical care
    • cover coughs and sneezes
      • cover mouth and nose with a tissue or use the inside of the elbow
      • throw used tissues in the trash
      • immediately wash hands with soap and water for ≥ 20 seconds or use hand sanitizer with ≥ 60% alcohol
    • if sick, wear a face mask when around other people
    • if not sick, do not wear a face mask unless caring for someone who is sick and cannot wear a face mask
    • clean and disinfect frequently touched surfaces daily
  • CDC recommendations for people in the United States exposed to a person with known or suspected COVID-19, other than healthcare workers or other critical infrastructure workers
    • guidance for household members, intimate partners, individuals providing care without using recommended infection control precautions, or close contact (< 6 feet) for prolonged period (duration not clear, perhaps greater than a few minutes)
    • for persons with exposure to symptomatic COVID-19 between 48 hours prior to symptom onset until discontinuation of home isolation
      • stay home until 14 days after last exposure and maintain distance of ≥ 6 feet from others at all times
      • self-monitor for symptoms
        • check temperature twice daily
        • watch for fever, cough, or shortness of breath
      • avoid contact with people at higher risk for severe illness unless they live in the same home and had same exposure
      • follow CDC guidance if symptoms develop
    • Reference - CDC public health recommendations for people in U.S. communities exposed to a person with known or suspected COVID-19, other than healthcare workers or other critical infrastructure workers (CDC 2020 Mar 30)
  • CDC recommendations after travel from areas with potential risk of exposure to COVID-19
    • for travelers from a country with widespread ongoing transmission or cruise ship/river boat travelers
      • stay home for 14 days after arrival and maintain a distance of ≥ 6 feet from others
      • self-monitor for symptoms
        • check temperature twice daily
        • watch for fever, cough, or shortness of breath
      • avoid contact with people at higher risk for severe illness unless they live in the same home and had same exposure
      • follow CDC guidance if symptoms develop
    • for travelers from a country with ongoing community transmission
      • practice social distancing by maintaining a distance of ≥ 6 feet from others and staying out of crowded places
      • be alert for symptoms including fever, cough, or shortness of breath
      • if symptoms develop, take temperature and follow CDC guidance
    • Reference - CDC public health recommendations after travel from areas with potential risk of exposure to COVID-19 (CDC 2020 Mar 30)
  • additional CDC guidance
    • interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease (COVID-19) (CDC 2020 Feb 12)
    • interim guidance for public health professionals managing people with COVID-19 in home care and isolation who have pets or other animals (CDC 2020 Mar 16)
    • information on water transmission and COVID-19 (CDC 2020 Apr 3)
    • interim guidance for administrators of United States K-12 schools and childcare programs can be found at CDC 2020 Mar 19 or in Chinese or in Spanish

Surviving Sepsis Campaign

National Institutes of Health (NIH)

  • National Institutes of Health (NIH) guideline on treatment of COVID-19 recommendations for infection control in the critical care setting
    • during aerosol-generating procedures on patients with COVID-19, fit-tested respirators or powered air-purifying respirators recommended over surgical masks, in addition to other personal protective equipment (PPE) such as gloves, gown, and eye protection (NIH Grade AIII)
    • use of aerosol-generating procedures in patients with COVID-19 should be minimized, with any necessary procedures performed in an airborne infection isolation room (AIIR) (NIH Grade AIII)
    • if possible, endotracheal intubation should be performed by healthcare workers with extensive airway management experience (NIH Grade AIII)
    • consider video laryngoscopy for intubation, if possible (NIH Grade CIII)
    • surgical masks along with other PPE recommended for healthcare workers
      • providing usual care for nonventilated patients with COVID-19 (NIH Grade BIII)
      • performing nonaerosol-generating procedures on mechanically ventilated patients with COVID-19 (NIH Grade BIII)
    • Reference - NIH COVID-19 Treatment Guideline (NIH 2020 Apr 21)

Efficacy of Public Health Interventions

  • Study Summary
    quarantine measures reported to reduce incidence and mortality during COVID-19 pandemic
    DynaMed Level3
    Details
    Critical_Care Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Care Pulmonary_Disordersquarantine measures reported to reduce incidence and mortality during COVID-19 pandemic (Cochrane Database Syst Rev 2020 Apr 8)04/22/2020 12:07:34 PMstudySummary
    • Cochrane Review based on Cochrane review of mostly modelling studies with noncomparative data
    • systematic review of 29 studies (25 modelling studies, including 10 on COVID-19 and 15 on severe acute respiratory syndrome [SARS] or Middle East respiratory syndrome [MERS], and 4 observational studies on SARS or MERS) evaluating quarantine measures to control COVID-19
    • meta-analysis not conducted due to diverse methods of analysis and outcomes
    • compared to no measures, quarantine of people exposed to confirmed or suspected cases of COVID-19 estimated to prevent
      • 44%-81% of potential cases in 4 modelling studies on COVID-19 or SARS
      • 31%-63% of potential deaths in 2 modelling studies on COVID-19 or SARS
    • addition of other measures (including school closures, travel restrictions, and social distancing) to quarantine alone reported to be associated with greater reduction in
      • new cases in 4 modelling studies on COVID-19
      • transmission of SARS-CoV-2 in 2 modelling studies on COVID-19
      • death in 2 modelling studies on COVID-19
    • consistent findings for addition of other measures in studies on SARS and MERS
    • compared to later implementation of quarantine measures, earlier quarantine measures reported to be associated with greater cost savings in 2 modelling studies on SARS
    • quarantine of travellers from country with declared outbreak reported to have small impact on reducing incidence and deaths in 2 modelling studies on SARS
    • PubMed32267544The Cochrane database of systematic reviewsCochrane Database Syst Rev202004084CD013574CD013574Reference - Cochrane Database Syst Rev 2020 Apr 8;4:CD013574
  • Study Summary
    multicomponent public health interventions reported to mitigate transmission of COVID-19 in Wuhan, China
    DynaMed Level3
    Details
    Hospital_Medicine Infectious_Diseases Internal_Medicinemulticomponent public health interventions reported to mitigate transmission of COVID-19 in Wuhan, China (JAMA 2020 Apr 10 early online)04/15/2020 05:24:17 PMstudySummary
    • Cohort Study based on noncomparative analysis of cohort study
    • 32,583 patients (median age 56 years) with confirmed COVID-19 infection between December 8, 2019 and March 8, 2020 in Wuhan, China were assessed
    • 5 events or nonpharmaceutical public health interventions potentially affecting virus transmission were assessed
      • no COVID-19-specific interventions (December 8 to January 9)
      • massive human movement due to Chinese New Year holiday (January 10-22)
      • implementation of cordons sanitaire (restriction of movement of people into or out of defined geographic area), traffic restriction, compulsory masks, cancellation of social gatherings, and home quarantine of confirmed or suspected cases (January 23 to February 1)
      • implementation of centralized quarantine and treatment of confirmed or suspected cases, quarantine of close contacts of confirmed cases in designated hospitals or facilities, and stay-at-home policy for all residents (February 2-16)
      • door-to-door and individual-to-individual symptom screening for all residents (February 17 to March 8)
    • confirmed cases per 1 million persons/day by events or public health interventions
      • 2 during no intervention
      • 45.9 during massive human movement
      • 162.6 during city lock down with traffic suspension and home quarantine
      • 77.9 during intensified measures with centralized quarantine and treatment
      • 17.2 during door-to-door screening
    • case rate among healthcare workers peaked to 617.4 per million persons/day during January 23 to February 1 period
    • effective reproduction number (Rt) (defined as mean number of secondary cases generated by typical primary case at time t)
      • > 3 before January 26
      • < 1 after February 6
      • < 0.3 after March 1
    • proportion of severe and critical cases by events or public health interventions
      • 53% during no intervention
      • 35% during massive human movement
      • 23.5% during city lock down with traffic suspension and home quarantine
      • 15.9% during intensified measures with centralized quarantine and treatment
      • 10.3% during door-to-door screening
    • confirmed cases per 1 million persons/day over whole period
      • 41.5 in general population
      • 130.5 in local health workers
      • 7.9 in infants < 1 year old
      • ranged from 2 to 5.4 in children and adolescents aged 1-19 years
    • PubMed32275295JAMAJAMA20200410Reference - JAMA 2020 Apr 10 early online, editorial can be found in JAMA 2020 Apr 10 early online
  • Study Summary
    duration of subsequent interventions to control SARS-CoV-2 transmission after relaxation of public health interventions reported to have to be of longer duration than relaxation period unless Rt maintained below 1.5 during relaxation period and could be lowered to < 0.5 during subsequent intervention
    DynaMed Level3
    Details
    Hospital_Medicine Infectious_Diseases Internal_Medicineduration of subsequent interventions to control SARS-CoV-2 transmission after relaxation of public health interventions reported to have to be of longer duration than relaxation period unless Rt maintained below 1.5 during relaxation period and could be lowered to < 0.5 during subsequent intervention (Lancet 2020 Apr 8 early online)04/15/2020 05:33:50 PMstudySummary
    • Modeling study based on modeling study
    • 13,415 confirmed cases of COVID-19 from mainland China outside Hubei province have been reported as of March 18, 2020
    • cities in mainland China outside Hubei province with adequate data served as basis for analysis
    • since implementation of public health interventions, instantaneous reproduction number (Rt) decreased and consistently remained < 1 in all selected cities
    • susceptible-infectious-recovered model was used to estimate potential effect of relaxing containment measures after first wave of infection
      • Stage 1: interventions implemented so that Rt = 1
      • Stage 2: interventions relaxed allowing Rt > 1
      • Stage 3: interventions from stage 1 implemented again so that Rt = 1
      • Stage 4: interventions more aggressive than those in stages 1 and 3 so that Rt < 1
    • model suggests that
      • relaxation of interventions to allow Rt > 1 results in exponential increase in total cases as function of duration of relaxation measures even if later aggressive interventions lower prevalence to prerelaxation level
      • duration of aggressive interventions would need to be longer than duration of relaxation period unless Rt maintained below 1.5 during intervention relaxation and could be lowered to < 0.5 during stage 4
    • PubMed32277878Lancet (London, England)Lancet20200408Reference - Lancet 2020 Apr 8 early online

Effects of Personal Protective Equipment on Healthcare Workers

  • Study Summary
    working in inpatient wards and wearing PPE > 6 hours/day associated with increased risk of skin reactions to PPE in healthcare workers caring for COVID-19 patients in China
    Details
    Critical_Care Dermatologic_Disorders Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Careworking in inpatient wards and wearing PPE > 6 hours/day associated with increased risk of skin reactions to PPE in healthcare workers caring for COVID-19 patients in China (Br J Dermatol 2020 Apr 7 early online)04/26/2020 07:34:34 PMstudySummary
    • Cross-Sectional Study based on cross-sectional study
    • 376 healthcare workers (78% female) in 5 hospitals in Wuhan, China and five regional hospitals surrounding Wuhan responded to survey between February 6-11, 2020 querying skin reactions and effects of wearing personal protective equipment (PPE)
    • overall, adverse skin reactions reported in 280 (74.5%), including
      • dryness or scales in 68.6%
      • papules or erythema in 60.4%
      • maceration in 52.9%
    • most commonly affected sites included hands, cheeks and nasal bridge
    • increased risk of adverse skin reactions in multivariate analysis associated with
      • duration with full body PPE > 6 hours/day (odds ratio [OR] 4.26, 95% CI 1.99-9.12)
      • working in inpatient wards (OR 2.44, 95% CI 1.37-4.37)
      • working in hospitals with more severe epidemic (OR 2.41, 95% CI 1.41-4.11)
      • female sex (OR 1.87, 95% CI 1.04-3.39)
    • PubMed32255197The British journal of dermatologyBr J Dermatol20200407Reference - Br J Dermatol 2020 Apr 7 early online
  • Study Summary
    wearing goggles or N95 mask > 6 hours/day associated with increased risk of adverse skin reactions in healthcare workers caring for COVID-19 patients in China
    Details
    Critical_Care Dermatologic_Disorders Family_Medicine Hospital_Medicine Infectious_Diseases Internal_Medicine Primary_Carewearing goggles or N95 mask > 6 hours/day associated with increased risk of adverse skin reactions in healthcare workers caring for COVID-19 patients in China (J Am Acad Dermatol 2020 May)04/26/2020 07:36:52 PMstudySummary
    • Cross-Sectional Study based on cross-sectional study
    • 542 healthcare workers in Hubei Province, China responded to a survey between January and February 2020 querying skin reactions and effects of wearing personal protective equipment (PPE)
    • 71.4% worked in isolation wards and 28.6% in fever clinics
    • overall, skin effects reported in 526 (97%), including
      • dryness/tightness in 70.3%
      • desquamation in 62.2%
      • tenderness in 56.8%
      • itching in 52.5%
      • erythema in 49.4%
      • maceration in 39.9%
      • fissure in 38.8%
      • burning/pain in 38%
      • papule in 32.9%
      • erosion and ulcer in 10.1%
    • sites involved included nasal bridge in 83.1%, cheek in 78.7%, hands in 74.5%, and forehead in 57.2%
    • increased risk of adverse skin effects associated with
      • wearing goggles > 6 hours (odds ratio [OR] 2.32, 95% CI 1.41-3.83)
      • hand hygiene > 10 times/day (OR 2.17, 95% CI 1.38-3.43)
      • wearing N95 mask > 6 hours (OR 2.02, 95% CI 1.35-3.01
    • wearing gloves > 6 hours/day or wearing face shield > 6 hours/day were not significantly associated with increased risk of adverse skin effects
    • PubMed32171808Journal of the American Academy of DermatologyJ Am Acad Dermatol202005018251215-12161215Reference - J Am Acad Dermatol 2020 May;82(5):1215

Additional Resources

  • PubMed32112714Lancet (London, England)Lancet20200226review of psychological impact of quarantine and how to reduce it during the COVID-19 outbreak can be found in Lancet 2020 Mar 14;395(10227):912
  • FDA guidance on respirators for healthcare personnel
    • FDA issues emergency use authorization to allow healthcare personnel to use industrial National Institute for Occupational Safety and Health (NIOSH)-approved respirators not currently regulated by FDA during the COVID-19 outbreak (FDA News Release 2020 Mar 2)
    • Critical_Care Hospital_Medicine Infectious_Diseases Internal_MedicineFDA issues Emergency Use Authorization permitting emergency usage of non-NIOSH approved respirators imported from and made in China, including KN95 respirators, provided they comply with certain performance and regulatory standards that can be verified by FDA (FDA emergency use authorization 2020 Apr 3)04/08/2020 04:41:37 PMFDA issues Emergency Use Authorization permitting emergency usage of non-NIOSH approved respirators imported from and made in China, including KN95 respirators, provided they comply with certain performance and regulatory standards that can be verified by FDA
      • must be manufactured by an entity that holds ≥ 1 National Institute for Occupational Safety and Health (NIOSH) approval for other respirator models in accordance with standards of authorization in other countries
      • must have regulatory authorization under a jurisdiction other than China that can be authenticated
      • acceptable performance must be confirmed (by applicable testing standards) and documented by recognized independent laboratory
      • References - FDA emergency use authorization 2020 Apr 3, FDA press release 2020 Apr 3
  • FDA guidance on sterilization of respirators
    • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues Emergency Use Authorization permitting emergency usage of Sterilucent Sterilization System to decontaminate compatible N95 or N95-equivalent respirators in hospital setting, enabling single-user reuse by clinicians (FDA emergency use authorization 2020 Apr 21)04/26/2020 07:39:27 PMFDA issues Emergency Use Authorization permitting emergency usage of Sterilucent Sterilization System to decontaminate compatible N95 or N95-equivalent respirators in hospital setting, enabling single-user reuse by clinicians
      • Sterilucent Sterilization Systems utilize vaporized hydrogen peroxide in multi-step 35-minute Flexible Cycle in chamber; after completion of cycle, decontaminated respirators must be allowed to aerate for ≥ 6 hours prior to each use
      • each compatible respirator (those that are placed in individual pouches and do not contain cellulose-based material) may be decontaminated up to 10 times for reuse by a single user
      • visibly soiled or damaged respirators cannot be decontaminated and must be discarded
      • other instructions for use are similar to those of other sterilization systems authorized for emergency decontamination of respirators (see fact sheet and instructions for healthcare facilities for details)
      • Reference - FDA emergency use authorization 2020 Apr 21
    • Critical_Care Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues Emergency Use Authorization permitting emergency usage of Battelle Critical Care Decontamination System (Battelle CCDS) for use in decontaminating compatible N95 or N95-equivalent respirators for reuse by healthcare personnel to prevent exposure to pathogens when respirators are in short supply during the COVID-19 pandemic(FDA Fact Sheet 2020 Mar 29, FDA Emergency Use Authorization letter 2020 Mar 28)04/01/2020 04:50:29 PMFDA issues Emergency Use Authorization permitting emergency usage of Battelle Critical Care Decontamination System (Battelle CCDS) for use in decontaminating compatible N95 or N95-equivalent respirators for reuse by healthcare personnel to prevent exposure to pathogens when respirators are in short supply during the COVID-19 pandemic
      • Battelle CCDS uses vapor phase hydrogen peroxide (VPHP) for decontamination by injecting VPHP into the decontamination chamber with exposure time of 150 minutes
      • compatible N95 respirators (respirators not made with cellulose-based material) may be decontaminated with Battelle CCDS a maximum of 20 times
      • visibly soiled or damaged respirators cannot be decontaminated and must be discarded
      • healthcare facilities must send respirators to Battelle for decontamination, which will be returned following decontamination
      • References - FDA Fact Sheet 2020 Mar 29, FDA Emergency Use Authorization letter 2020 Mar 28
    • Critical_Care Hospital_Medicine Infectious_Diseases Internal_MedicineFDA issues Emergency Use Authorization permitting emergency usage of STERIS Sterilization Systems for use in decontamination of compatible N95 or N95-equivalent respirators in hospital setting, enabling reuse by clinicians (FDA press release 2020 Apr 10)04/14/2020 11:37:33 AMFDA issues Emergency Use Authorization permitting emergency usage of STERIS Sterilization Systems for use in decontamination of compatible N95 or N95-equivalent respirators in hospital setting, enabling reuse by clinicians
      • STERIS systems use vaporized hydrogen peroxide (which fills sterilization chamber, penetrates device, and sterilizes exposed surfaces) in a pre-programmed cycle for terminal sterilization of properly prepared (cleaned, rinsed and dried) medical devices
      • each compatible respirator (those that are individually pouched and do contain cellulose-based material) may be decontaminated for reuse up to 10 times for a single user
      • visibly soiled or damaged respirators cannot be decontaminated and must be discarded
      • healthcare facilities looking to use the system must
        • provide healthcare personnel with a fact sheet and authorized instructions for use
        • store decontaminated respirators in Tyvek pouch, on which number of decontamination cycles can be tracked along with name of individual user
      • References - FDA press release 2020 Apr 10, FDA emergency use authorization 2020 Apr 10
    • Critical_Care Hospital_Medicine Infectious_Diseases Internal_MedicineFDA issues Emergency Use Authorization permitting emergency usage of Advanced Sterilization Products (ASP) STERRAD sterilization systems for use in decontamination of compatible N95 or N95-equivalent respirators in hospital setting, enabling reuse by clinicians (FDA emergency use authorization 2020 Apr 11)04/15/2020 04:59:20 PMFDA issues Emergency Use Authorization permitting emergency usage of Advanced Sterilization Products (ASP) STERRAD sterilization systems for use in decontamination of compatible N95 or N95-equivalent respirators in hospital setting, enabling reuse by clinicians
      • ASP STERRAD systems allow vaporized hydrogen peroxide (59% nominal H2O2, which is transformed into gas plasma using electrical energy) to perfuse chamber, facilitating contact with all surfaces under sub-ambient conditions before atmospheric pressure is reestablished
      • model cycles that are authorized to decontaminate compatible respirators potentially exposed to COVID-19 include STERRAD 100S Cycle, STERRAD NX Standard cycle, and STERRAD 100NX Express Cycle
      • each compatible respirator (those that are individually pouched and do not contain cellulose-based material) may be decontaminated up to 2 times for reuse by a single user
      • other instructions for use are similar to those of other sterilization systems authorized for emergency decontamination of respirators (see fact sheet and instructions, to be provided to healthcare personnel, for details)
      • References - FDA emergency use authorization 2020 Apr 11
    • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues Emergency Use Authorization permitting emergency usage of Stryker Sterizone VP4 Sterilizer with N95 Respirator Decontamination Cycle to decontaminate N95 or N95-equivalent respirators in hospital setting, enabling reuse by clinicians (FDA Emergency Use Authorization 2020 Apr 14)04/22/2020 12:08:38 PMFDA issues Emergency Use Authorization permitting emergency usage of Stryker Sterizone VP4 Sterilizer with N95 Respirator Decontamination Cycle to decontaminate N95 or N95-equivalent respirators in hospital setting, enabling reuse by clinicians
      • Sterizone VP4 Sterilizer uses vaporized hydrogen peroxide and ozone in a pre-programmed cycle typically used for general instruments, flexible endoscopes, and rigid-channel devices
      • each compatible respirator (respirators not made with cellulose, paper, natural rubber, or latex) may be decontaminated up to 2 times for reuse by a single user
      • other instructions for use are similar to those of other sterilization systems authorized for emergency decontamination of respirators (see fact sheet to be provided to healthcare personnel for details)
      • References - FDA Emergency Use Authorization 2020 Apr 14, FDA Fact Sheet for Healthcare Personnel 2020 Apr 14
  • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues Emergency Use Authorization permitting emergency usage of B. Braun Space and Outlook Pumps for tracheal delivery of continuously nebulized medications into a nebulizer in patients suspected of having COVID-19 infection to decrease exposure of healthcare providers to such patients (FDA emergency use authorization 2020 Apr 11)04/16/2020 05:13:00 PMFDA issues Emergency Use Authorization permitting emergency usage of B. Braun Space and Outlook Pumps for tracheal delivery of continuously nebulized medications into a nebulizer in patients suspected of having COVID-19 infection to decrease exposure of healthcare providers to such patients (FDA emergency use authorization 2020 Apr 11)

Guidelines and Resources

Guidelines and Resources

Guidelines

International Guidelines

  • World Health Organization (WHO) technical guidance for coronavirus disease (COVID-19) can be found at WHO Coronavirus Disease (COVID-19)
  • American Thoracic Society (ATS) International Task Force interim guidance on COVID-19 management (pending empirical evidence) can be found at ATS 2020 Apr 3 PDF
  • World Confederation for Physical Therapy/International Confederation of Cardiorespiratory Physical Therapists/Australian Physiotherapy Association/Canadian Physiotherapy Association/Associazione Riabilitatori dell'Insufficienza Respiratoria/Association of Chartered Physiotherapists in Respiratory Care (WCPT/ICCrPt/APTA/CPA/ArIR/ACPRC) recommendations to guide clinical practice on physiotherapy management for COVID-19 in the acute hospital setting can be found at APTA 2020 Mar 23 PDF
  • PubMed32275978ChestChest20200407Fleischner Society multinational consensus statement on the role of chest imaging in patient management during the COVID-19 pandemic can be found in Chest 2020 Apr 7 early online
  • International Liaison Committee on Resuscitation (ILCOR) guidance on COVID-19 infection risk to rescuers from patients in cardiac arrest can be found at ILCOR 2020 Apr 10
  • PubMed32160345Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and GynecologyUltrasound Obstet Gynecol20200311International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) interim guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals can be found in Ultrasound Obstet Gynecol 2020 Mar 11 early online

United States Guidelines

Centers for Disease Control and Prevention (CDC) Guidelines
  • overall interim guidance on coronavirus (COVID-19) can be found at CDC Coronavirus (COVID-19) or in Chinese, Korean, Spanish, Vietnamese
  • evaluation and management
    • guidance on evaluating and testing persons for coronavirus disease (COVID-19) can be found at CDC 2020 Apr 27
    • interim guidance for public health personnel evaluating persons under investigation and asymptomatic close contacts of confirmed cases at their home or non-home residential settings can be found at CDC 2020 Mar 14
    • interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19) can be found at CDC 2020 Apr 3
    • interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease (COVID-19) can be found at CDC 2020 Feb 12
    • considerations for discontinuation of transmission-based precautions and disposition of hospitalized patients with COVID-19 can be found at CDC 2020 Mar 23
    • information for pediatric healthcare providers can be found at CDC 2020 Apr 17
    • interim guidelines for collecting, handling, and testing clinical specimens from patients under investigation for coronavirus disease 2019 (COVID-19) can be found at CDC 2020 Apr 14
    • interim laboratory biosafety guidelines for handling and processing specimens associated with coronavirus disease 2019 (COVID-19) can be found at CDC 2020 Mar 31
    • interim guidance for emergency medical services (EMS) systems and 911 public safety answering points (PSAPs) for COVID-19 in United States can be found at CDC 2020 Mar 10
  • infection prevention and control
    • interim infection prevention and control recommendations for patients with suspected or confirmed coronavirus disease 2019 (COVID-19) in healthcare settings can be found at CDC 2020 Apr 13
    • recommendation regarding use of cloth face coverings, especially in areas of significant community-based transmission can be found at CDC 2020 Apr 3 or in Chinese, Korean, Spanish, or Vietnamese
    • interim considerations for infection prevention and control recommendations for coronavirus disease (COVID-19) in inpatient obstetric healthcare settings can be found at CDC 2020 Apr 4
    • guidance for preventing the spread of coronavirus disease (COVID-19) in homes can be found at CDC 2020 Feb 14 or in Chinese, Korean, Spanish, Vietnamese
    • guidance on preparing for COVID-19 in long-term care facilities and nursing homes can be found at CDC 2020 Mar 21
    • interim guidance on mass gatherings or large community events can be found at CDC 2020 Mar 15
    • interim guidance for businesses and employers can be found at CDC 2020 Mar 21 or in Chinese, Korean, Spanish, Vietnamese
  • risk assessment
    • interim United States guidance for risk assessment and public health management of healthcare personnel with potential exposure in a healthcare setting to patients with coronavirus disease (COVID-19) can be found at CDC 2020 Apr 15
    • public health recommendations after travel-associated COVID-19 exposure can be found at CDC 2020 Mar 30
    • interim guidance for implementing safety practices for critical infrastructure workers who may have had exposure to a person with suspected or confirmed COVID-19 can be found at CDC 2020 Apr 8 or in Chinese, Korean, Spanish, Vietnamese
    • public health recommendations for people in United States communities exposed to a person with known or suspected COVID-19, other than healthcare workers or other critical infrastructure workers can be found at CDC 2020 Mar 30
  • guidance for healthcare facilities
    • interim guidance for outpatient and ambulatory care settings: responding to community transmission of COVID-19 in the United States can be found at CDC 2020 Apr 7
    • guidance on mitigating healthcare personnel staffing shortages can be found at CDC 2020 Apr 13
    • interim guidance containing criteria for return to work for healthcare personnel with confirmed or suspected COVID-19 can be found at CDC 2020 Apr 13
    • guidance for pharmacies during the COVID-19 pandemic can be found at CDC 2020 Apr 3 or in Chinese, Korean, Spanish, or Vietnamese
    • interim infection control guidance on COVID-19 for personnel at blood and plasma collection facilities can be found at CDC 2020 Mar 21
    • interim guidance on infection prevention and control for dental settings during the COVID-19 response can be found at CDC 2020 Apr 7
    • healthcare professional preparedness checklist for transport and arrival of patients with confirmed or possible COVID-19 can be found at CDC 2020 Feb 12
    • steps healthcare facilities can take now to prepare for COVID-19 can be found at CDC 2020 Mar 6
    • use of personal protective equipment (PPE) when caring for patients with confirmed or suspected COVID-19 can be found at CDC 2020 Mar 30 PDF
  • interim guidance for health departments
    • information for health departments on reporting a patient under investigation (PUI) or presumptive positive and laboratory-confirmed cases of COVID-19 can be found at CDC 2020 Mar 1
    • supplemental guidance for childcare programs that remain open can be found at CDC 2020 Apr 21 or in Chinese, Korean, Spanish, Vietnamese
    • considerations for infection prevention and control for alternate care sites can be found at CDC 2020 Apr 6
    • CDC/Occupational Safety and Health Administration (OSHA) interim guidance for meat and poultry processing workers and employers can be found at CDC 2020 Apr 26
    • interim guidance for public health professionals managing people with COVID-19 in home care and isolation who have pets or other animals can be found at CDC 2020 Apr 23
    • interim infection prevention and control guidance for veterinary clinics during the COVID-19 response can be found at CDC 2020 Apr 22 or in Chinese, Korean, Spanish, Vietnamese
    • information on drinking water, recreational water, and wastewater and COVID-19 can be found at CDC 2020 Apr 23
    • interim guidance for administrators of United States K-12 schools and childcare programs can be found at CDC 2020 Mar 12 or in Chinese, Korean, Spanish, Vietnamese
    • pandemic preparedness resources can be found at CDC 2020 Feb 15
Other United States Guidelines
  • Critical_Care Hospital_Medicine Infectious_Diseases Internal_Medicine Pulmonary_DisordersNational Institutes of Health (NIH) COVID-19 treatment guideline (NIH 2020 Apr 21)04/23/2020 04:21:50 PMNational Institutes of Health (NIH) COVID-19 treatment guideline can be found at NIH 2020 Apr 21
  • Infectious Diseases Society of America (IDSA)
  • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign guideline on management of critically ill patients with coronavirus disease 2019 (COVID-19) can be found in Crit Care Med 2020 Mar 27 early onlinePDF, also published in Intensive Care Med 2020 Mar 28 early onlinefull-text
  • American College of Obstetricians and Gynecologists (ACOG) practice advisory on novel coronavirus 2019 (COVID-19) can be found at ACOG 2020 Mar 13
  • United States Department of Health and Human Services (DHHS) interim guidance on COVID-19 and persons with HIV can be found at AIDSinfo 2020 Apr 21
  • American Heart Association (AHA) interim guidance for healthcare providers during COVID-19 outbreak: CPR and emergency cardiovascular care can be found at AHA 2020 Mar PDF
  • American College of Cardiology (ACC) COVID-19 clinical guidance for the cardiovascular care team can be found at ACC 2020 Mar 6 PDF
  • PubMed32270695CirculationCirculation20200409American Heart Association/American Academy of Pediatrics/American Association for Respiratory Care/American College of Emergency Physicians/Society of Critical Care Anesthesiologists/American Society of Anesthesiologists (AHA/AAP/AARC/ACEP/SOCCA/ASA) interim guidance on basic and advanced life support in adults, children, and neonates with suspected or confirmed COVID-19 can be found in Circulation 2020 Apr 9 early onlinefull-text
  • PubMed32259247Pain medicine (Malden, Mass.)Pain Med20200407American Academy of Pain Medicine (AAPM) guidance on pain management best practices from multispecialty organizations during the COVID-19 pandemic and public health crises can be found in Pain Med 2020 Apr 7 early online full-text
  • Centers for Medicare and Medicaid Services (CMS) guidance on
    • infection control and prevention of coronavirus disease 2019 (COVID-19) in nursing homes can be found at CMS 2020 Mar 13 PDF
    • infection control and prevention concerning coronavirus disease (COVID-19): FAQs and considerations for patient triage, placement and hospital discharge can be found at CMS 2020 Mar 4 PDF
  • American Academy of Ophthalmology (AAO) coronavirus updates for ophthalmologists can be found at AAO 2020 Apr 19

United Kingdom Guidelines

National Institute for Health and Care Excellence (NICE) Guidelines
Other United Kingdom Guidelines
  • Public Health England (PHE) information on COVID-19 can be found at PHE COVID-19
  • Royal College of Obstetricians and Gynecologists/Royal College of Midwives/Royal College of Paediatrics and Child Health/Public Health England/Health Protection Scotland (RCOG/RCM/RCPCH/PHE/HPS) guidance for healthcare professionals on coronavirus (COVID-19) infection in pregnancy can be found at RCOG 2020 Apr 17
  • Association of Anaesthetists of Great Britain and Ireland (AAGBI) guidelines on
    • disaster planning during a COVID-19 outbreak can be found at AAGBI 2020 Apr 2
    • anaesthetic management of patients during a COVID-19 outbreak can be found at AAGBI 2020 Apr 2
  • British Thyroid Association/Society for Endocrinology (BTA/SfE) guidance
    • statement regarding issues specific to thyroid dysfunction during the COVID -19 pandemic can be found at BTA 2020 Mar 25 PDF
    • advice regarding resource-limited treatment of thyrotoxicosis during the COVID-19 pandemic can be found at BTA 2020 Mar 25 PDF
    • advice for patients with thyroid cancer during the COVID-19 pandemic can be found at BTA 2020 Mar 23 PDF

Canadian Guidelines

  • Public Health Agency of Canada (PHAC)
  • Ontario Ministry of Health guidance for the health sector on COVID-19 can be found at Health.gov.on.ca 2020 Apr 20
  • Canadian Cardiovascular Society (CCS) guidance on COVID-19 and concerns regarding use of cardiovascular medications, including ACEi/ARB/ARNi, low-dose ASA and non-steroidal anti-inflammatory drugs (NSAIDS) can be found at CCS 2020 Mar 20 PDF
  • L’Institut national d’excellence en santé et en services sociaux (INESSS) rapid response guidance on COVID-19 and chloroquine/hydroxychloroquine can be found at INESSS 2020 Apr 4 [French]

European Guidelines

European Centre for Disease Prevention and Control (ECDC) Guidelines
  • European Centre for Disease Prevention and Control (ECDC) information on COVID-19 can be found at ECDC COVID-19
    • guidance on contact tracing: public health management of persons, including healthcare workers, having had contact with COVID-19 cases in the European Union can be found at ECDC 2020 Apr 9
    • guidance for discharge and ending isolation in the context of widespread community transmission of COVID-19 can be found at ECDC 2020 Apr 8
    • guidance on the use of face masks in the community - reducing COVID-19 transmission from potentially asymptomatic or pre-symptomatic people through the use of face masks can be found at ECDC 2020 Apr 8
    • guidance on infection prevention and control for COVID-19 in healthcare settings can be found at ECDC 2020 Mar 31
    • guidance on disinfection of environments in healthcare and nonhealthcare settings potentially contaminated with SARS-CoV-02 can be found at ECDC 2020 Mar 26
    • advice on the use of cloth face masks and sterilisation of respirators and surgical masks as an alternative in healthcare settings with suspected or confirmed COVID-19 cases if there is a shortage of specialised surgical masks and respirators can be found at ECDC 2020 Mar 26
    • guidance on health system contingency planning during widespread transmission of SARS-CoV-2 with high impact on healthcare services can be found at ECDC 2020 Mar 17
    • case definition and European surveillance for COVID-19 can be found at ECDC 2020 Mar 2
    • guidance for wearing and removing personal protective equipment in healthcare settings for care of patients with suspected or confirmed COVID-19 can be found at ECDC 2020 Feb 28
    • checklist for hospitals preparing for reception and care of coronavirus 2019 (COVID-19) patients can be found at ECDC 2020 Feb 26
    • guideline on use of nonpharmaceutical measures to delay and mitigate impact of 2019-nCoV can be found at ECDC 2020 Feb 10
    • guidance on personal protective equipment (PPE) needs in healthcare settings for the care of patients with suspected or confirmed novel coronavirus (2019-nCoV) can be found at ECDC 2020 Feb 7
Other European Guidelines
  • PubMed32208497Swiss medical weeklySwiss Med Wkly20200324150w20235w20235Association for Geriatric Palliative Medicine (FGPG) 2019 pandemic guideline on palliative care for elderly and frail patients at home and in residential and nursing homes can be found in Swiss Med Wkly 2020 Mar 23;150:w20235full-text
  • PubMed32264898World journal of emergency surgery : WJESWorld J Emerg Surg202004071512525National Congress of Italian Hospital Surgeons/Italian Society of Cardiology/Italian Society for Trauma and Emergency Surgery/Italian Society of Surgical Oncology/Italian Surgical Society for Elderly People/Italian Society of Surgical Pathophysiology/Italian Society of Endoscopic Surgery/Italian Society of Anaesthesia Analgesia Resuscitation and Intensive Care (ACOI/SIAARTI/SIC/SICUT/SICO/SICG/SIFIPAC/SICE/SIAARTI) operational directives on surgery in COVID-19 patients can be found in World J Emerg Surg 2020 Apr 7;15(1):25full-text
  • European Association of Urology (EAU) COVID-19 recommendations can be found at EAU 2020 Apr PDF
  • Government of Spain Ministry of Health (Gobierno de Espana Ministerio de Sanidad) guidelines on
  • Italian Society of Infectious and Tropical Diseases (SIMIT) guidelines on
    • therapeutic and supportive management for patients with COVID-19 coronavirus infection can be found at SIMIT 2020 Mar PDF [Italian]
    • treatment of persons with COVID-19 can be found at SIMIT 2020 Mar 13 PDF [Italian]
  • Republic of Portugal High Commission for Migrations (Republica Portuguesa ACM) COVID-19 measures, guidelines, and recommendations can be found at ACM 2020 Apr 16 [Portuguese and English]

Asian Guidelines

  • Chinese Center for Disease Control and Prevention guidance on new coronavirus pneumonia can be found at Chinese CDC [Chinese]
  • Japanese National Institute of Infectious Diseases (NIID)
    • guideline on infection control for novel coronavirus infections can be found at NIID 2020 Apr 7 [Japanese]
    • pathogen detection manual can be found at NIID 2020 Mar 19 [Japanese}
  • Japanese Association for Infectious Diseases (JAID) information on new coronavirus infection (COVID-19) can be found at JAID 2020 Apr 23 [Japanese]
  • Taiwan Centers for Disease Control and Prevention coronavirus disease (2019) information on disease totals in Taiwan, global numbers, and links to resources in 7 languages can be found at Taiwan CDC 2020 Apr 23
  • PubMed32029004Military Medical ResearchMil Med Res202002067144Wuhan University Novel Coronavirus Management and Research Team/China International Exchange & Promotive Association for Medical and Health Care rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCov) can be found in Mil Med Res 2020 Feb 6;7(1):4full-text, commentary can be found in Mil Med Res 2020 Apr 4;7(1):16

Central and South American Guidelines

  • Pan American Health Organization (PAHO)
    • laboratory guideline on detection and diagnosis of novel coronavirus (2019-nCoV) infection can be found at PAHO 2020 Feb 1PDF or in SpanishPDF
    • requirements and technical specifications of personal protective equipment (PPE) for novel coronavirus (2019-ncov) in healthcare settings can be found at PAHO 2020 Feb 6PDF
    • interim laboratory biosafety guideline on handling and transport of samples associated with novel coronavirus 2019 (2019-nCoV) can be found at PAHO 2020 Jan 28PDF or in SpanishPDF
    • technical specifications of medical devices for case management of COVID-19 in healthcare settings can be found at PAHO 2020 Mar 3PDF or in SpanishPDF

Australian and New Zealand Guidelines

Review Articles

Travel Information

Patient Information

References

General References Used

  1. Centers for Disease Control and Prevention (CDC). Coronavirus Disease 2019 (COVID-19). (CDC 2020 )

Recommendation Grading Systems Used

  • Society of Critical Care Medicine (SCCM) recommendation grading system
    • strength of recommendation
      • Strong - desirable effects of adherence to recommendation will clearly outweigh undesirable effects
      • Weak - desirable effects of adherence to recommendation will probably outweigh undesirable effects, but panel is not confident about trade-offs (either because benefits and downsides are closely balanced, or some evidence is low-quality and thus uncertainty remains regarding benefits and risks)
      • Best practice statement - ungraded strong recommendation where evidence is hard to summarize or assess using GRADE methodology
    • quality of evidence
      • High - randomized controlled trials (RCTs)
      • Moderate - downgraded RCTs or upgraded observational studies
      • Low - well-done observational studies with RCTs
      • Very low - downgraded controlled studies or expert opinion or other evidence
    • Reference - SCCM Surviving Sepsis Campaign guideline on management of critically ill patients with coronavirus disease 2019 (COVID-19) (Crit Care Med 2020 Mar 27 early onlinePDF)
  • Infectious Diseases Society of America (IDSA) grading system for recommendations
    • strength of recommendation
      • Strong recommendation - most people should receive recommended course of action
      • Conditional recommendation - be prepared to help people make a decision that is consistent with their own values/decision aids and shared decision making
      • Knowledge gap - additional research needed for recommendation
    • certainty of evidence
      • High - very confident that the true effect lies close to that of the estimate of the effect
      • Moderate - moderately confident in the effect estimate: true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
      • Low - confidence in the effect estimate is limited: true effect may be substantially different from the estimate of the effect
      • Very low - very little confidence in the effect estimate: true effect is likely to be substantially different from the estimate of effect
    • References
      • IDSA guideline on management of patients with COVID-19 (IDSA 2020 Apr 11)
      • IDSA guideline on infection prevention in patients with suspected or known COVID-19 (IDSA 2020 Apr 27)
  • National Institutes of Health (NIH) recommendation rating scheme
    • strength of recommendation
      • A - strong recommendation for the statement
      • B - moderate recommendation for the statement
      • C - optional recommendation for the statement
    • quality of evidence for recommendation
      • I - ≥ 1 randomized trials with clinical outcomes and/or validated laboratory endpoints
      • II - ≥ 1 more well-designed, nonrandomized trials or observational cohort studies
      • III - expert opinion
    • Reference - NIH COVID-19 treatment guideline (NIH 2020 Apr 21)

DynaMed Editorial Process

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Special Acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
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