Coronavirus SARS-CoV2 infection (COVID-19)

Essential Evidence

Last Updated on 2020-05-22 © 2020 John Wiley & Sons, Inc.

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Authors:
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

Editor:
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 weekly by the editor-in-chief (a family physician and professor of epidemiology) with support from other EE+ editors and staff. We are 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 Since preprint servers have not been peer-reviewed, and data and conclusions may change, information from them should be used with great caution if at all.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. Most common symptoms are fever, cough, myalgias, and dyspnea.C
  • 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, a strategy of waiting until at least 3 days free of fever without antipyretics, 3 days without respiratory symptoms, and at least 7 days after onset of symptoms is recommended by CDC. C
  • Treatment is primarily supportive, and includes monitoring oxygen saturation. Corticosteroids are not routinely recommended; they may be considered for patients with sepsis or septic shock. Remdesivir shortens the duration of hospitalization and may reduce mortality slightly, but other outcomes have not yet been reported. B
  • The overall case fatality rate is estimated to be 1% and is higher in older patients and those with comorbidities. 65 As of May 20th, the Johns Hopkins Center for Health Security reports that there have been 92,149 deaths and 1,532,974 confirmed cases in the US (6.0% case fatality rate), 6,029 deaths and 80,537 confirmed cases in Canada (7.5% case fatality rate), and 35,422 deaths and 250,141 confirmed cases in the UK (14.2% case fatality rate). These rates are higher than the true case and infected fatality rates due to the large number of undiagnosed mild and asymptomatic cases. B

Background

  • COVID-19 (coronavirus disease 2019) is a viral lower respiratory infection first reported in Wuhan City, China that has rapidly spread to become a pandemic. It is caused by novel coronavirus named 2019-nCoV and more recently SARS-CoV2.

Incidence

  • Information about incidence and the case fatality rate are evolving. Peak incidence predictions nationally and by state for the US are provided by the modeling group at the University of Washington.
  • Several other Web sites and the Johns Hopkins Coronavirus Resource Center provide detailed information on new cases, total cases, and deaths that are updated daily.
  • The initial report (preprint server) of a community serosurvey is from Santa Clara County, California (population 1.9 million). At the time of the study there had been 956 confirmed cases, and they had some of the earliest reported cases (January 31, 2020). On April 3rd and 4th, they obtained serum from 3330 adults and children. After adjusting for age distribution in the population and trying to account for false positives and negatives, they estimate a prevalence of 2.5% to 4.2% of antibodies to SARS-CoV2. That provides a range of 48,000 to 81,000 infections, far higher than the number reported number on April 1 of 956 cases.
  • In a study of 220 women admitted for delivery in New York in late March/early April 2020, all were tested and 15.4% were positive for SARS-CoV2, most of whom were asymptomatic. 60

Other Impact

  • Based on modeling by the COVID-19 research unit at Imperial College in London, the case fatality ratio is estimated to be 0.9% overall (95% credible interval 0.4% to 1.4%). It is lowest in children (0.002%), and is higher with increasing age (0.08% for 30 to 39, 0.60% for 50 to 59, 2.2% for 60 to 69, 5.1% for 70 to 79 and 9.3% for 80 and older). Mortality is also higher in those with comorbidities such as hypertension, diabetes and chronic cardiopulmonary conditions. To some extent, this may be a matter of confounding as these conditions are more common in older persons.
  • These estimates are likely to change as the epidemic evolves, as there is currently incomplete case ascertainment, especially in the US, while some infected persons who will die in the next 2 weeks are not yet counted in the fatality data. Data from Italy and China found similar case-fatality rates when stratified by age, with the exception of a higher rate in Italy for those 80 years and older. Since data were not reported for those 90 and older in China, this could still represent an effect of greater age in Italy within this group.
  • A time series study of hospitals designated to provide primary coronary interventions in northern Italy determined the daily rate of hospitalizations for acute coronary syndromes was significantly lower in the six weeks after the first case of COVID-19 than for the six weeks immediately preceding and the same time period the prior year (13.3 per day during COVID-19 vs. 18.0 and 18.9 per day, respectively). 97

Causes of the Condition

  • The cause of COVID-19 is the novel coronavirus SARS-CoV-2.
  • Coronaviruses are enveloped, single-stranded RNA viruses that include those that caused a large-scale epidemic of severe acute respiratory syndrome (SARS) in 2002-3 and the Middle-East respiratory syndrome (MERS), a persistent epidemic in the Arabian Peninsula since 2012. There also several widely circulating species that cause mild respiratory tract infections in humans. 74

Pathophysiology

  • COVID-19 infection ("COronaVirus Disease 2019") is caused by a novel coronarvirus SARS-CoV-2. It is the 7th coronavirus reported to cause disease in humans.
  • Like SARS-CoV, SARS-CoV-2 is in the subgenus sarbecovirus. It is more closely related genetically to SARS than to MERS (Middle Eastern Respiratory Syndrome). 16
  • The genome has been sequenced. 16
  • The incubation period is a median of 5 days, and 97.5% who develop symptoms will do so within 11.5 days. About 1% may develop symptoms more than 14 days after exposure. 36
  • The median duration of viral shedding in survivors is 20 days, based on early data from Wuhan City, China. 18
  • It is thought that the virus is spread mainly through respiratory droplets and by those in close contact, within about 6 feet or 2 meters. However, the virus can be spread by asymptomatic persons. 27 A report from Singapore has been published in MMWR, a country where there was very careful contact tracing. They estimated that 10 of 157 (6.4%) locally-acquired cases were infected by someone who was presymptomatic (e.g. 1 to 3 days before symptom onset) based on contact with the presymptomatic individual and no contact with any symptomatic persons. A modeling study estimated even higher rates of infection from persons with mild or asymptomatic disease. 48
  • Researchers report a cluster of 10 COVID-19 cases that were most likely spread from one infected person at a restaurant in Guangzhou, China. The index case and 3 family members traveled from Wuhan on January 23, 2020 and had lunch at a small restaurant. The index case reportedly did not feel ill at lunch, but developed cough and fever later that day. Within 2 weeks, 9 other people who were in the restaurant became ill; 4 family members of the index case, 3 members of a family sitting at a neighboring table and 2 family members sitting at the table on the other side. The distance between tables was 3 feet, and the exposure time to the other two families was about one hour. The investigators could find no other exposures to COVID-19 for the other two infected families. The investigators hypothesize that the infection may have been spread by the air-conditioning unit. If so, this report has significant implications as countries open up restaurants and other business venues requiring close physical proximity. 64
  • In a series of 94 patients published in Nature Medicine, researchers estimated that 44% (95% CI 25% to 69%) were infected by presymptomatic or asymptomatic index patients. Shedding declined over a median 21-day period. They estimate that patients were infectious 2.3 days prior to symptom onset (95% CI 0.8 to 3.0 days), with a peak infectiousness at 0.7 days prior to symptom onset (95% CI -0.2 to 2.0 days).
  • A series of 116 patients with COVID-19 found that coinfection was fairly uncommon, most often with rhinovirus (6.9%), RSV (5.2%) and other coronaviruses (4.3%). 58
  • Close contacts of 100 confirmed COVID-19 patients in Taiwan were identified and followed to ascertain what proportion of them became infected with the coronavirus. Among 2,761 contacts, there were 22 secondary infections, an attack rate of 0.7% (95% CI, 0.4%-1.0%) The attack rate was highest among the 1,818 individuals exposed within 5 days of symptom onset (1.0%) compared to those with later exposure (0 cases from 852 contacts). The rate was also highest among household contacts (4.6%) and non-household family contacts (5.3%). Contacts with only pre-symptomatic exposure had a 0.9% incidence of infection. This study suggests that isolation of infected individuals is insufficient to halt transmission of COVID-19. 78
  • The virus can also remain on surfaces like cardboard (up to 24 hours) and steel or plastic (up to 72 hours). However, it is not known how long before the level of viral pathogen on the surface is below the amount needed to cause human infection, and the effect of environmental factors on duration. 28
  • Researchers evaluated 96 consecutive patients hospitalized with COVID-19, 22 of whom had mild disease and 74 had severe disease. They performed daily PCR assays of sputum, saliva, blood, urine and stool. The researchers evaluated 3497 samples and found SARS-CoV-2 RNA in 59% of the patients. The median duration of fecal shedding of SARS-CoV-2 RNA was 22 days compared with 18 days in the respiratory samples and 16 days in the serum samples. It was detected in only a single urine sample. Patients with severe disease shed virus for 1 week longer than those with mild disease (21 days vs. 14 days, respectively). 68

Risk Factors

Risk Factor
Living in or traveling to an endemic area for SARS-CoV-2
Risk factors for severe COVID-19 infection include increasing age, comorbidities (diabetes, COPD, asthma, heart disease), elevated CRP, LDH, ALT or AST, decreased albumin, lymphopenia, and neutrophilia.