Coronavirus SARS-CoV2 infection (COVID-19)

Essential Evidence

Last Updated on 2020-09-28 © 2020 John Wiley & Sons, Inc.

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Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia
Mindy A. Smith, MD, MS, Clinical Professor, Department of Family Medicine, Michigan State University
Henry C. Barry, MD, MD, MS, Professor Emeritus, Michigan State University
Pete Yunyongying, MD, FACP, Associate Professor , Carle-Illinois College of Medicine, University of Illinois
John Hickner MD, MS, Professor Emeritus, University of Illinois-Chicago

Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia

Overall Bottom Line

  • EDITOR'S NOTE: This topic has been made freely available and is being updated regularly. We are at times linking to preprint servers and providing direct links to articles where possible, and most of this literature has been made freely available. As preprint work becomes peer reviewed and formally published, we will update the citations. Since preprint servers have not been peer-reviewed, and the data and conclusions may change, information from them should be used with great caution if at all.
  • Suspect COVID-19 when the virus is circulating in the population and a patient reports signs and symptoms of respiratory tract infection, or less commonly fever and neurologic symptoms or thrombosis. Most common symptoms are fever, cough, myalgias, and dyspnea; loss of taste and smell are also common. Approximately 40% of all patients are asymptomatic but appear to be as infectious as symptomatic patients. B
  • Preventive measures include hand washing, surface cleaning, case isolation, quarantine of contacts for 14 days, school and university closures, and general social distancing/sheltering at home. Modeling indicates that only by doing all of these measures can the number of severe cases requiring ventilation not overwhelm hospitals.B
  • Mask and isolate patients on presentation to a healthcare facility and obtain PCR from nasopharynx and oropharynx. Also test for influenza and strep throat if clinically suspected. C
  • The combination of age and CRP can be used to identify patients at low, moderate and high risk of severe illness (see Prognosis section below).B
  • Patients can be considered cured using a test-based strategy (recovery from fever without antipyretics and without respiratory symptoms plus 2 negative PCR tests 24 hours apart). For outpatients in settings where tests are not widely available, the CDC recommends that isolation be maintained for at least 10 days after illness onset and at least 3 days (72 hours) after recovery, defined as: at least 3 days free of fever without antipyretics, 3 days without respiratory symptoms, and at least 7 days after onset of symptoms. C
  • Treatment is primarily supportive and includes monitoring oxygen saturation.
  • Remdesivir shortens the duration of hospitalization (11 vs. 15 days) and may reduce mortality slightly. 108B
  • Corticosteroids have been shown in a large UK trial with 6425 patients to be highly effective at reducing mortality in patients with COVID-19 who are mechanically ventilated (NNT = 7) or who are on oxygen (NNT = 20) but not in hospitalized patients not requiring oxygen. 161 Their use also decreases the likelihood of requiring mechanical ventilation. 171B
  • Multiple randomized controlled trials have confirmed that hydroxychloroquine is not effective for severe disease, mild disease, early disease, or as post-exposure prophylaxis, and is associated with a higher risk of adverse events. 173 105A
  • The overall infection fatality rate is estimated to be 0.5% to 0.9% and is higher in older patients and those with comorbidities. 65 As of September 24th, the Johns Hopkins Center for Health Security reports that there have been 984,813 deaths and 32,356,829 confirmed cases worldwide, 203,147 deaths and 6,997,468 confirmed cases in the US (2.9% case fatality ratio), 9,304 deaths and 151,982 confirmed cases in Canada (6.1% case fatality ratio), and 42,025 deaths and 425,765 confirmed cases in the UK (9.9% case fatality ratio). Mortality rates per 100,000 are 62.0 in the US, 25.1 in Canada, and 63.2 in the UK. These rates are higher than the true case and infected fatality rates due to the large number of undiagnosed mild and asymptomatic cases. B

Management of Special Populations


  • To date, studies have found no evidence of the virus in breastmilk or amniotic fluid samples. 25 24
  • Two case series of 10 and 38 births respectively found no evidence of infection by PCR in the infants. Vertical transmission of infection therefore seems unlikely. 39 38
  • WHO interim guidance recommends that mother and infant be allowed to remain together and have skin to skin contact, regardless of whether they or their infant have COVID-19 infection.
  • A study 215 pregnant women who delivered in New York in late March or early April 2020 found that 13.5% were SARS-CoV2-positive but asymptomatic, and 1.9% were SARS-CoV2 positive and symptomatic. 60
  • A study in a single UK hospital compared rates of stillbirth, preterm birth, cesarean delivery, or NICU admissions during the pandemic and during the same period one year before. Rates of stillbirth were significantly higher during the pandemic (6.98 vs.1.19 per 1000 births, p <0.05). The cause is not known, but the authors hypothesized it could be due to asymptomatic COVID-19 infection, worse prenatal care, or thrombotic complications affecting the placenta. The other outcomes did not increase during the pandemic. 160
  • A systematic review concluded that pregnant women less likely to manifest COVID-19 symptoms but more likely to need intensive care than non-pregnant women. 173

Infants and Children

  • Infants and children generally have milder illness and a milder clinical presentation. In one series of 171 children with confirmed infection with COVID-19, 41% had fever, and 16% had no signs or symptoms. Only 3 required ICU support, all of whom had serious comorbidities (hydronephrosis, leukemia, and intussusception). 29
  • In an Italian case series of 100 childhood cases presenting to pediatric emergency departments, only 54% presented with fever, 44% with cough and 11% with shortness of breath. Mortality ranged from 0% to 0.6% in the Italian study and 4 other studies summarized by the authors. 81
  • A case series from China Table 1 identified 2,143 cases, of which 731 (34.2%) were laboratory confirmation cases and 1,412 (65.8%) suspected cases. Cases were initially identified based on clinical signs and symptoms and exposure history. The median age was 7 years. More cases were boys (56.6%) than girls (43.4%). Of the confirmed cases, 12.9% were asymptomatic, 43.1% mild, 41% moderate, 2.5% severe and 0.4% critical. Severe and critical cases were more prevalent in those under 1 year of age. On average, children were less severely ill compared to adult cases. 73
  • A CDC report in MMWR of pediatric hospitalizations in 14 states from 3/1/20 to 7/25/20 found a rate of 8 hospitalizations/100,000 children. Highest rate was <2 years (25/100,000) and was much higher for Hispanic and Black children (16.4 and 10.5 per 100,000, respectively, compared to non-Hispanic White children (2.1 per 100,000). One in 3 hospitalized children required intensive care.
  • In a study of 91 children with COVID-19 identified by contact tracing in South Korea, 2% remained asymptomatic, 60% had respiratory symptoms, and 55% had non-specific systemic symptoms. Viral shedding was 14 to 20 days, longer in those who were more symptomatic. 170
  • Multisystem inflammatory syndrome
  • A case series from Bergamo, Italy reported an outbreak of an inflammatory disorder in children that is similar to Kawasaki disease. They compared 19 children diagnosed prior to 2/17/20 with 10 diagnosed since that time. The monthly incidence since 2/17/20 was 30x higher than previously, and children were older (mean 7.5 vs. 3.0 years) and sicker (more with shock, cardiac involvement, and need for adjunctive corticosteroids). 92
  • This syndrome is now referred to as multisystem inflammatory syndrome. Five case series describe the characteristics of children with this syndrome. Overall, 381 children were included in these studies, 115 (30%) were black, 276 (72%) had lab-confirmed COVID-19, and 143 (38%) also met criteria for Kawasaki Disease. Overall, 88% had gastrointestinal symptoms, 53% had nausea or vomiting and 58% had abdominal pain. Rash occurred in 60% of the children and desquamation, only reported in two studies, occurred in 7 of 28 (25%). Two-hundred twelve (56%) 36% had redness or swelling of the lips or mucous membranes. Coronary artery dilation occurred in 11% of the children, myocardial dysfunction in 32% and shock in 34%. Only three of the studies reported chest radiograph data; 101 of the 224 (45%) were abnormal. 124 125 123