Critical Findings on COVID-19: Select Publications from the National Academies of Sciences, Engineering, and Medicine (2021)

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Rapid Expert Consultation on Severe Illness in Young Adults for the COVID-19 Pandemic (March 14, 2020) Rapid Expert Consultation on Severe Illness in Young Adults for the COVID-19 Pandemic (March 14, 2020) March 14, 2020 Kelvin Droegemeier, Ph.D. Office of Science and Technology Policy Executive Office of the President Eisenhower Executive Office Building 1650 Pennsylvania Avenue, NW Washington, DC 20504 Robert Kadlec, M.D. Assistant Secretary for Preparedness and Response 200 Independence Avenue, SW Washington, DC 20201 Dear Drs. Droegemeier and Kadlec: Attached is a brief response to your question on whether reports of severe illness in younger adults in Italy may represent a genetic change to the virus. As explained in the note, the reports from Italy of severe illness in young adults may not represent a change in the pattern of susceptibility, as even the earliest reports from China indicated severe illness among young adults, though at a lower frequency than among older persons. At the present time, the genetic make up of the virus circulating in Italy appears to be the same as that found in other countries of Europe. The enclosed document was prepared by staff of the National Academies of Sciences, Engineering, and Medicine based on input from Trevor Bedford, David Walt, and me. My colleagues and I hope this input is helpful to you as you continue to guide the nation’s response in this ongoing public health crisis. Respectfully, Harvey V. Fineberg, M.D., Ph.D. Chair Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats 1 Copyright National Academy of Sciences. All rights reserved. 

Rapid Expert Consultation on Severe Illness in Young Adults for the COVID-19 Pandemic (March 14, 2020) Recent reports from Italy describe severe illness requiring ventilatory support in younger adults without underlying comorbidities. At this time, there are not enough data to indicate whether these cases are a small fraction of a large number of infected young adults or represent a shift in the severity spectrum toward more severe disease in younger adults. Of note, China reported 12.0% (67/557) of patients 15-49 years of age developed severe illness (compared to 28.8% [44/153] in those ≥65 years), 1 so severe illness in young adults has not been an uncommon occurrence from the start of the pandemic. 2 Unofficial reports from the outbreak in the state of Washington similarly note the occurrence of severe illness in young adults. A determination of any change in the incidence or severity spectrum of illness in different segments of the population requires a systematic analysis of longitudinal data, currently unavailable. Obtaining these data through the tracking of natural patient histories and outcomes is an important component of managing the epidemic. This analysis would produce updated calculations of risk factors by age group and tracking of any changes over time. We need to be prepared to routinely collect and share these data as the epidemic progresses in the United States. If changes in risk factor by age group were to occur, this could potentially be a result of mutations in the circulating virus. On genomic epidemiologic analysis, the Italian outbreak is primarily driven by the “Lombardy clade” or “A2.” 3 This clade has a P314L mutation in ORF1b and also R203K and G204R in N. However, this same virus is distributed widely throughout Europe, and there are not enough data reported from other European countries to conclude whether the Italian experience is atypical. The epidemic expanded rapidly in Italy prior to an increase in cases in other European countries. If Italy is reporting an increase in severity and deaths among young adults compared to other European countries, this could be due to the stage of the epidemic, health system shortcomings, or different reporting methods rather than virus evolution. Although COVID-19 typically has caused higher rates of severe illness and mortality in older populations and those with underlying illnesses, it is important not to downplay the potential seriousness of this infection in younger age groups. While data are gathered and analyzed, messaging should stress that everyone should be concerned about COVID-19 and take appropriate steps to protect their health, the health of their loved ones and neighbors, and the health of the public at large. 1 Guan et al. 2020. Clinical characteristics of coronavirus disease 2019 in China. New England Journal of Medicine. DOI: 10.1056/NEJMoa2002032. 2 The manuscript defines “severe” as per the American Thoracic Society guidelines and not all severe cases may have required mechanical ventilation. In addition, the manuscript does not delineate by age group how many severe cases had underlying illnesses (38.7% of severe cases overall had a coexisting disorder). Metlay et al. 2019. Diagnosis and treatment of adults with community-acquired pneumonia: An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. American Journal of Respiratory and Critical Care Medicine 200(7):e45-e67. DOI: 10.1164/rccm.201908-1581ST. 3 See https://nextstrain.org/ncov?branchLabel=aa&label=clade:A2&m=div. 2 Copyright National Academy of Sciences. All rights reserved.