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COVID-19 (Novel Coronavirus)

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 breath(1)
  • 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 cases(1)

Also Called

  • 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 may include
      • hospitalized patients with compatible clinical features in order to inform infection control
      • symptomatic individuals at high risk for complications, such as older adults and individuals with chronic medical conditions or immunocompromise
      • persons (including healthcare personnel) with history of
        • close contact with known case of COVID-19 within 14 days of symptom onset
        • history of travel from affected geographic areas with 14 days of symptoms onset
    • Reference - CDC Interim Guidance for Healthcare Professionals 2020 Mar 9

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]

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 Infectious_Diseases Internal_Medicine Pulmonary_Disorders634,835 confirmed cases of coronavirus disease 2019 (COVID-19) including 29,891 deaths worldwide reported by World Health Organization (WHO) as of March 29, 2020 (WHO Situation Report 2020 Mar 29)03/30/2020 02:22:40 PM634,835 confirmed cases of coronavirus disease 2019 (COVID-19) including 29,891 deaths worldwide reported by World Health Organization (WHO) as of March 29, 2020
    • European Region
      • 361,031 cases including 21,427 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed cases*New Confirmed cases*Total Deaths
        Italy92,4725,97410,023
        Spain72,2488,1895,690
        Germany52,5473,965389
        France37,1454,6032,311
        United Kingdom17,0932,546 1,019
        Switzerland13,1521,048235
        Netherlands9,7621,159 639
        Belgium9,1341,850 353
        Austria8,29159468
        Turkey7,4021,704108
        Portugal5,170902100
        Israel3,86540515
        Norway3,84526420
        Sweden3,447401102
        Czechia2,66338411
        Ireland2,41529436
        Denmark2,20115565
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Region of the Americas
      • 120,798 cases including 1,973 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        United States103,32118,0931,668
        Canada4,75773955
        Brazil3,41750292
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Western Pacific Region
      • 102,803 cases including 3,626 deaths
      • countries reporting > 2,000 cases
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        China82,3561263,306
        Republic of Korea9,583105152
        Australia3,96633116
        Malaysia2,32015927
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Eastern Mediterranean Region
      • 42,777 cases including 2,668 deaths
      • countries most affected
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        Iran35,4083,0762,517
        Pakistan1,52629113
        Saudi Arabia1,203994
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • South-East Asia Region
      • 3,709 cases including 139 deaths
      • countries most affected
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        Thailand1,3882527
        Indonesia1,155109102
        India97925525
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • African Region
      • 3,005 cases including 51 deaths
      • countries most affected
        CountryTotal Confirmed Cases*New Confirmed Cases*Total Deaths
        South Africa1,187171
        Algeria4094226
        Burkina Faso14603
        *Case counts are informed by local and regional testing capacity and reporting policies.
    • Reference - WHO Situation Report 2020 Mar 29 PDF
  • United States
  • real-time dashboard of COVID-19 cases can be found at Johns Hopkins Center for Systems Science and Engineering (CSSE)
  • COVID-19 cases in the United States can be found at The Weather Channel (An IBM Business)

Risk factors

  • interim exposure risk categories for persons in United States established by Centers for Disease Control and Prevention (CDC)
    • guidance applies to United States-bound travelers and people in United States who may have been exposed to SARS-CoV-2
    • high risk persons include those living in same household as, being intimate partner of, or providing care in nonhealthcare setting (such as home) for a person with symptomatic laboratory-confirmed COVID-19 without using recommended precautions for home care and home isolation
    • medium risk persons include those
      • with close contact with a person with symptomatic laboratory-confirmed COVID-19 not meeting high risk category
      • on an aircraft, being seated within 6 feet (2 meters) or within 2 seats in any direction of a traveler with symptomatic laboratory-confirmed COVID-19
      • living in same household as, intimate partner of, or providing care in nonhealthcare setting (such as home) for a person with symptomatic laboratory-confirmed COVID-19 while consistently using recommended precautions for home care and home isolation
      • travel
        • from a country with widespread sustained transmission or sustained community transmission
        • on a cruise ship or river boat
    • low risk persons include those in same indoor environment (such as a classroom or healthcare waiting room) with a person with symptomatic laboratory-confirmed COVID-19 for prolonged period of time but not meeting the definition for close contact
    • no identifiable risk for persons with interaction with patients with symptomatic laboratory-confirmed COVID-19 that does not meet high, medium, or low risk categories
    • Reference - CDC Interim United States Guidance for Risk Assessment 2020 Mar 22

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 with 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
  • infected persons are thought to be most contagious when they are most symptomatic, though some spread may be possible before 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 1-11, 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
    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
    Infectious_Diseases Internal_Medicineon 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 (Lancet 2020 Feb 20 early online)03/04/2020 02:11:20 PMstudySummary
    • 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

History and Physical

History and Physical

Clinical Presentation

  • 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
  • common symptoms include1
    • fever
    • cough
    • shortness of breath
  • Study Summary
    fever, fatigue, and cough most common clinical features in adults with COVID-19 pneumonia
    Details
    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 PMstudySummary
    • 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, between 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
        • acute respiratory distress syndrome (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 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 (APACHE II) 12 points
        • Sequential Organ Failure Assessment (SOFA) 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
      • 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 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
      • 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 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
        • 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
      • PubMed32007143Lancet (London, England)Lancet20200130Reference - Lancet 2020 Feb 15;395(10223):507
  • Study Summary
    wide spectrum of clinical features and disease severity in children with SARS-CoV2-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-CoV2-infection in China (N Engl J Med 2020 Mar 18 early online)03/24/2020 07:02:35 PMstudySummary
    • 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)
    • 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 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 x 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

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 may include
      • hospitalized patients with compatible clinical features in order to inform infection control
      • symptomatic individuals at high risk for complications, such as older adults and individuals with chronic medical conditions or immunocompromise
      • persons (including healthcare personnel) with history of
        • close contact with known case of COVID-19 within 14 days of symptom onset
        • history of travel from affected geographic areas with 14 days of symptoms onset
    • 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 9

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
          • if collected, combine in same tube as nasopharyngeal swab
          • may be collected as only specimen if other swabs unavailable
        • nasopharyngeal wash/aspirate or nasal aspirate
      • 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 Mar 21
  • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign recommendations for specimen collection in intubated and mechanically ventilated adults with suspected COVID-19
  • FDA issues emergency use authorization for point-of-care Cepheid Xpert Xpress SARS-CoV-2 test (FDA News Release 2020 Mar 21)
  • FDA issues emergency use authorization for Hologic Panther Fusion SARS-COV-2 assay and Laboratory Corporation of America (LabCorp) COVID-19 RT-PCR test (FDA News Release 2020 Mar 16)
  • FDA issues policy update on developing and authorizing tests for COVID-19 (FDA News Release 2020 Mar 16)
  • Critical_Care Infectious_Diseases Internal_Medicine Pulmonary_DisordersFDA issues emergency use authorization for 2019-nCoV real-time PCR diagnostic panel at qualified laboratories designated by CDC (FDA News Release 2020 Feb 4)02/05/2020 10:31:33 AMFDA issues emergency use authorization for 2019-nCoV real-time PCR diagnostic panel at qualified laboratories designated by CDC (FDA News Release 2020 Feb 4)

Blood tests

  • 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 1-20, 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 Infectious_Diseases Internal_Medicine Pulmonary_Disordersbilateral ground glass opacities common finding on chest computed tomography in patients with COVID-19 pneumonia (AJR Am J Roentgenol 2020 Mar 14 early online)03/30/2020 09:12:57 AMstudySummary
    • Cohort StudyCohort StudySystematic Review based on 1 systematic review and 2 retrospective cohort studies
    • 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
    • 101 patients (mean age 44 years, range 17-75 years) with COVID-19 pneumonia who had chest CT were evaluated
      • CT findings included
        • ground glass opacities in 86.1%
        • vascular enlargement in 71.3%
        • mixed ground glass opacities and consolidation in 64.4%
        • traction bronchiectasis in 52.5%
        • reticulation in 48.5%
        • consolidation in 43.6%
        • bronchial wall thickening in 28.7%
        • subpleural bands in 27.7%
        • centrilobular nodules in 22.8%
        • architectural distortion in 21.8%
        • pleural effusions in 13.9%
        • intrathoracic lymph node enlargement in 1%
      • distribution of features
        • lung region
          • bilateral in 82.2%
          • unilateral in 9.9%
        • craniocaudal distribution
          • lower lung predominant in 54.5%
          • no craniocaudal distribution in 31.7%
          • upper lung predominant in 5.9%
        • transverse distribution
          • peripheral in 87.1%
          • no transverse distribution in 4%
          • central in 1%
        • scattered distribution
          • multifocal in 54.5%
          • diffuse in 31.7%
          • focal in 5.9%
      • PubMed32125873AJR. American journal of roentgenologyAJR Am J Roentgenol202003031-61Reference - AJR Am J Roentgenol 2020 Mar 3 early online
    • 83 patients (mean age 45 years) with COVID-19 pneumonia who had CT imaging were evaluated
      • CT findings included
        • ground glass opacities in 97.6%
        • linear opacities in 65.1%
        • consolidation in 63.9%
        • interlobular septal thickening in 62.7%
        • crazy-paving pattern in 36.1%
        • spiderweb sign in 25.3%
        • bronchial wall thickening in 22.9%
        • subpleural curvilinear line in 20.5%
        • lymph node enlargement in 8.4%
        • pleural effusion in 8.4%
        • nodule in 7.2%
        • reticulation in 4.8%
        • pericardial effusion in 4.8%
      • bilateral lung disease in 95.2% with median 5 involved lobes
      • PubMed32118615Investigative radiologyInvest Radiol20200229Reference - Invest Radiol 2020 Feb 29 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 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%
    • Reference - N Engl J Med 2020 Mar 18 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

Supportive management

Investigational therapies

  • no antiviral drugs are currently approved for patients with COVID-191
  • 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
      • remdesivir (adenosine nucleotide analogue) 100-200 mg/day IV for 5-10 days in clinical trials
      • lopinavir/ritonavir (protease inhibitor) 400 mg/100 mg orally twice daily for 14 days in 1 trial
      • 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
      • hydroxychloroquine1
        • optimal dosing for COVID-19 unknown
        • anecdotal dosing reported
          • 400 mg twice daily on day 1 followed by 400 mg once daily for 5 days, with extension to 10 days depending on clinical response
          • 400 mg twice on day 1 followed by 200 mg twice daily for 4 days
          • 600 mg twice on day 1 followed by 400 mg daily for 2-5 days
      • 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
      • arbidol hydrochloride
      • recombinant human interferon
      • Yinhu Qingwen granula
      • T89
      • anti-programmed death-1 (anti-PD-1)
      • IV immunoglobulin
      • aviptadil
      • nitric oxide
      • N-acetylcysteine plus Fuzheng Huayu
      • immunoglobulin from recovered patients
      • natural killer cells
    • list of COVID-19 related clinical trials can be found at ClinicalTrials.gov
  • 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 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)

Prognosis

  • Study Summary
    overall mortality rate 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 rate 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
    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
    DynaMed Level2
    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
    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

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.

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 glove; 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)

  • CDC interim recommendations for infection prevention and control for patients with suspected or confirmed COVID-19
    • guidance intended for United States healthcare settings only
    • minimize chance for exposures
      • 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 facemasks and tissues (putting a facemask 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
          • inform infection prevention and control services, local and state public health authorities, and other healthcare staff as appropriate
        • 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 non-urgent outpatient visits
      • adherence to standard, contact, and airborne precautions
        • 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 facemask 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
        • 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 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)
            • facemasks 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 disinfection prior to re-use
        • specimen collection
          • limit number of healthcare personnel present during procedure; visitors should not be present
          • health care providers in room should wear N-95 or higher respirators (or facemasks 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
      • 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
          • screen visitors for symptoms of acute respiratory illness prior to entry
          • evaluate risk to health of visitor
          • 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
          • CLINICIANS' PRACTICE POINT

            Asymptomatic high risk individuals should remain quarantined in a location determined by public health officials. Asymptomatic medium risk individuals should remain at home or comparable setting, avoid congregate settings, limit public activities, and practice social distancing to the extent possible.

        • 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 non-dedicated, non-disposable equipment to manufacturer's instructions and facility policies
        • ensure environmental cleaning and disinfection procedures are followed
        • 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 Mar 10)
  • duration of transmission-based precautions for persons under investigation and patients with confirmed COVID-19
    • discontinuation of isolation precautions determined on case-by-case basis in conjunction with local, state, and federal health authorities
    • factors to consider include
      • resolution of fever without antipyretics
      • improvement in signs and symptoms
      • negative testing with COVID-19 molecular assay from ≥ 2 consecutive sets of paired nasopharyngeal and throat swabs collected ≥ 24 hours apart
    • patients may be discharged from healthcare facility when clinically indicated
    • isolation should be maintained at home if patient is discharged prior to decision to discontinue transmission-based precautions
    • Reference - CDC interim considerations for discontinuation of transmission-based precautions and disposition of hospitalized patients with COVID-19 (CDC 2020 Mar 10)
  • CDC interim guidance on movement restrictions and public activities for persons with potential exposure to SARS-CoV-2 exposure based on risk category and symptoms
    • for symptomatic persons
      • high risk individuals
        • immediate isolation with consideration of public health orders
        • public health assessment to determine need for medical evaluation
        • if medical evaluation is necessary
          • diagnostic testing guided by CDC person of interest definition to determine who to test
          • pre-notify receiving health care facilities and emergency medical services (if needed)
          • air travel only by medical transport
          • local travel only by medical transport or in private vehicle with symptomatic patient wearing face mask
      • medium risk individuals
        • self-isolation
        • public health assessment to determine need for medical evaluation;
        • if medical evaluation is necessary
          • diagnostic testing guided by CDC person of interest definition to determine who to test
          • pre-notify receiving health care facilities and emergency medical services (if needed)
          • air travel only by medical transport
          • local travel only by medical transport or in private vehicle with symptomatic patient wearing face mask
      • low risk individuals or individuals at no identifiable risk
        • self-isolation and social distancing
        • seek health advice to determine need for medical evaluation
        • diagnostic testing guided by CDC person of interest definition to determine who to test
        • postpone travel on commercial conveyances until no longer symptomatic
    • for asymptomatic persons
      • high risk individuals
        • quarantined in a location determined by public health officials
        • no public activities
        • daily active monitoring based on local priorities, if possible
        • air travel only by medical transport and local travel only by medical transport or in private vehicle with symptomatic patient wearing face mask
      • medium risk individuals
        • close contacts, travelers from mainland China (outside Hubei Province) or Iran, and travelers from other countries with widespread transmission
          • remain at home or comparable setting
          • practice social distancing
          • self-monitor
          • postpone additional long-distance travel on commercial conveyance
        • travelers from country with sustained community transmission should practice social distancing and self-monitor
      • no restrictions for low risk individuals
    • Reference - CDC interim United States guidance for risk assessment and public health management of persons with potential coronavirus disease (COVID-19) exposures: geographic risk and contacts of laboratory-confirmed cases (CDC 2020 Mar 22)
  • 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 Mar 12)
    • interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease (COVID-19) (CDC 2020 Feb 12)
    • 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 6)
    • 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 10)
  • CDC interim guidance for health departments
    • 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 (CDC 2020 Feb 24)
    • 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
    • interim United States guidance for risk assessment and public health management of persons with potential coronavirus disease (COVID-19) exposures: geographic risk and contacts of laboratory-confirmed cases (CDC 2020 Mar 7)
    • 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 1)
    • information on water transmission and COVID-19 (CDC 2020 Mar 10)
    • interim guidance for administrators of United States K-12 schools and childcare programs can be found at CDC 2020 Mar 12 or in Chinese or in Spanish
    • pandemic preparedness resources (CDC 2020 Feb 15)

Surviving Sepsis Campaign

  • Society of Critical Care Medicine (SCCM) Surviving Sepsis Campaign Guidelines on Management of Critically Ill Adults with COVID-19 recommendations for infection control
    • for aerosol-generating procedures
      • fitted respirator masks (N95, FFP2, or equivalent) are recommended for healthcare workers in addition to other personal protective equipment including gloves, gown, and eye protection (SCCM Best practice statement)
      • performance of procedure in negative pressure room recommended (SCCM Best practice statement)
    • use of surgical/medical masks in addition to other personal protective equipment (PPE) recommended for
    • if endotracheal intubation is required, it should be performed by a trained and experienced provider using airborne precautions
    • Reference - SCCM Surviving Sepsis Campaign guideline on management of critically ill patients with coronavirus disease 2019 (COVID-19) (SCCM 2020 Mar 20 PDF)

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 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)

Guidelines and Resources

Guidelines and Resources

Guidelines

International Guidelines

United States Guidelines

  • Centers for Disease Control and Prevention (CDC)
    • overall interim guidance on coronavirus (COVID-19) can be found at CDC Coronavirus (COVID-19) or in Chinese or in Spanish
    • evaluation and management
      • interim guidance on evaluating and testing persons for coronavirus disease (COVID-19) can be found at CDC 2020 Mar 24
      • 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 Mar 7
      • interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease (COVID-19) can be found at CDC 2020 Feb 12
      • interim considerations for discontinuation of transmission-based precautions and disposition of hospitalized patients with COVID-19 can be found at CDC 2020 Mar 23
      • interim guidance for pediatric healthcare providers can be found at CDC 2020 Mar 12
      • 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 Mar 24
      • interim laboratory biosafety guidelines for handling and processing specimens associated with coronavirus disease 2019 (COVID-19) can be found at CDC 2020 Mar 18
      • 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 Mar 10
      • interim infection prevention and control recommendations for coronavirus disease (COVID-19) in inpatient obstetric healthcare settings can be found at CDC 2020 Feb 18
      • interim guidance for preventing the spread of coronavirus disease (COVID-19) in homes and residential communities can be found at CDC 2020 Feb 14 or in Chinese or in Spanish
      • interim 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
    • 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 Mar 7
      • interim United States guidance for risk assessment and public health management of persons with potential coronavirus disease (COVID-19) exposures: geographic risk and contacts of laboratory-confirmed cases can be found at CDC 2020 Mar 22
    • interim guidance for healthcare facilities
      • interim guidance containing criteria for return to work for healthcare personnel with confirmed or suspected COVID-19 can be found at CDC 2020 Mar 16
      • 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
      • sequence for putting on personal protective equipment can be found at CDC 2020 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
      • 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 Mar 1
      • information on water transmission and COVID-19 can be found at CDC 2020 Mar 10
      • interim guidance for administrators of United States K-12 schools and childcare programs can be found at CDC 2020 Mar 12 or in Chinese or in Spanish
      • pandemic preparedness resources can be found at CDC 2020 Feb 15
  • 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 at SCCM 2020 Mar 20 PDF
  • 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 Mar 20

United Kingdom Guidelines

  • Public Health England (PHE) information on COVID-19 can be found at PHE COVID-19
  • National Institute for Health and Care Excellence (NICE) COVID-19 rapid guidelines on
  • Royal College of Obstetricians and Gynecologists/Royal College of Midwives/Royal College of Paediatrics and Child Health/Public Health England/Health Protection Scotland guidance for healthcare professionals on coronavirus (COVID-19) infection in pregnancy can be found at RCOG 2020 Mar 28
  • Association of Anaesthetists of Great Britain and Ireland (AAGBI) guidelines on
    • disaster planning during a COVID-19 outbreak can be found at AAGBI 2020 Mar 19
    • anaesthetic management of patients during a COVID-19 outbreak can be found at AAGBI 2020 Mar 19

Canadian Guidelines

European Guidelines

  • European Centre for Disease Prevention and Control (ECDC) information on COVID-19 can be found at ECDC COVID-19
    • 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
    • guidance on infection prevention and control for COVID-19 in healthcare settings can be found at ECDC 2020 Mar 12
    • guidance on novel coronavirus (SARS-CoV-2) - discharge criteria for confirmed COVID-19 cases can be found at ECDC 2020 Mar 10
    • 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
    • guidance on public health management of persons, including health care workers, having had contact with COVID-19 cases in the European Union can be found at ECDC 2020 Feb 25
    • 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

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 Mar 19 [Japanese]
    • pathogen detection manual can be found at NIID 2020 Mar 4 [Japanese}
  • Japanese Association for Infectious Diseases (JAID) information on new coronavirus infection (COVID-19) can be found at JAID 2020 Mar 27 [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 Mar 30

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

Australian and New Zealand Guidelines

Travel Information

Patient Information

References

General References Used

  1. Centers for Disease Control and Prevention (CDC). Coronavirus Disease 2019 (COVID-19) . (CDC 2020 Mar 22)

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) (SCCM 2020 Mar 23 PDF)

DynaMed Editorial Process

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  • DynaMed content includes Practice-Changing Updates, with support from our partners, McMaster University and F1000.

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.
  • Editorial Team role definitions
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