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Frequently Asked Questions on Diagnosis, Transmission, and Epidemiology of SARS-CoV-2

David Heymann, BA, MD, DTM&H
Sharon R. Lewin, AO, FRACP, PhD, FAHMS
Jens D. Lundgren, MD, DMSc
Vikramjit Mukherjee, MD
Paul E. Sax, MD
Lynora Saxinger, MD, FRCPC, CTropMed
Released: July 8, 2020
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Anand S, Montez-Rath M, Han J, et al. Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study. Lancet. 2020;396;1335.

Bobay LM, O’Donnell AC, Ochman H. Recombination events are concentrated in the spike protein region of Betacoronaviruses. PLoS Genet. 2020;16:e1009272.

Buonsenso D, De Rose C, Moroni R, et al. SARS-CoV-2 infections in Italian schools: preliminary findings after one month of school opening during the second wave of the pandemic. medRxiv. October 11, 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.10.10.20210328v1. Accessed April 4, 2021.

Callaway E. The coronavirus is mutating - does it matter? Nature. 2020;585:174-177.

Centers for Disease Control and Prevention. New COVID-19 variants. January 15, 2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. Interim: implications of the emerging SARS-CoV-2 variant VOC 202012/01. December 29, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-emerging-variant.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. Symptoms of coronavirus. Updated December 22, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. COVID-19 pandemic planning scenarios. Updated September 10, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. Operational considerations for adapting a contact tracing program to respond to the COVID-19 pandemic. Updated December 9, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/operational-considerations-contact-tracing.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. Duration of isolation and precautions for adults with COVID-19. Updated October 19, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. Public health guidance for community-related exposure. Updated December 3, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/php/public-health-recommendations.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. How to protect yourself & others. Updated December 31, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html. Accessed April 4, 2021.

Centers for Disease Control and Prevention. Interim guidance for use of pooling procedures in SARS-CoV-2 diagnostic, screening, and surveillance testing. Updated October 23, 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/lab/pooling-procedures.html. Accessed April 4, 2021.

Cheng HW, Jian SW, Liu DP, et al. Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset. JAMA Intern Med. 2020;180:1156.

Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med. 2020;383:2291-2293.

Dagan M, Barda, M, Kepten E, et al. BNT162b2 mRNA COVID-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;[Epub ahead of print].

European Centre for Disease Prevention and Control. Risk related to the spread of new SARS-CoV-2 variants of concern in the EU/EEA – first update. January 21, 2021. Available at: https://www.ecdc.europa.eu/sites/default/files/documents/COVID-19-risk-related-to-spread-of-new-SARS-CoV-2-variants-EU-EEA-first-update.pdf. Accessed April 4, 2021.

Foundation for Innovative New Diagnostics. COVID-19 diagnostics & testing. Available at: https://www.finddx.org/covid-19/. Accessed April 4, 2021.

Gandhi M, Yokoe DS, Havlir DV. Asymptomatic transmission, the Achilles’ heel of current strategies to control Covid-19. N Engl J Med. 2020;382:2158.

GISAID. Available at: https://www.gisaid.org/epiflu-applications/phylodynamics/. Accessed April 4, 2021.

Ioannidis JPA. Infection fatality rate of COVID-19 inferred from seroprevalence data. Bulletin of the World Health Organization;BLT.20.265892. Available at: https://www.who.int/bulletin/online_first/BLT.20.265892.pdf. Accessed April 4, 2021.

Ismail SA, Saliba V, Lopez Bernal, J, et al. SARS-CoV-2 infection and transmission in educational settings: cross-sectional analysis of clusters and outbreaks in England. medRxiv. August 24, 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.08.21.20178574v1. Accessed April 4, 2021.

Korea Centers for Disease Control and Prevention. Findings from investigation and analysis of re-positive cases. May 19, 2020. Available at: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030&act=view&list_no=367267&nPage=1. Accessed April 4, 2021.

Kwok KO, Lai F, Wei WI, et al. Herd immunity—estimating the level required to halt the COVID-19 epidemics in affected countries. J Infect. 2020;80:e32.

Lauer SA, Grantz KH, Bi Q, et al. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172:577-582.

Li N, Wang X, Lv T. Prolonged SARS‐CoV‐2 RNA shedding: not a rare phenomenon. J Med Virol. 2020a;92:2286-2287.

Li Y, Yao L, Li J, et al. Stability issues of RT‐PCR testing of SARS‐CoV‐2 for hospitalized patients clinically diagnosed with COVID‐19. J Med Virol. 2020b;92:903-908.

Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020a;10.1038/s41591-020-0965-6.

Long Q-X, Liu B-Z, Deng H-J, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020b;26:845-848.

Manzanares-Meza LD, Medina-Contreras O. SARS-CoV-2 and influenza: a comparative overview and treatment implications. Bol Med Hosp Infant Mex. 2020;77:262-273.

Olson SJ, Azziz-Baumgartner E, Budd AP, et al. Decreased influenza activity during the COVID-19 pandemic—United States, Australia, Chile, and South Africa, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1305-1309.

Otte Im Kampe E, Lehfeld AS, Buda S, et al. Surveillance of COVID-19 school outbreaks, Germany, March to August 2020. Euro Surveill. 2020;25:2001645.

Plante JA, Liu Y, Liu J, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature. 2021;592:116-121.

Pollán M, Pérez-Gómez B, Pastor-Barriuso R, et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020;396:535.

Premraj A, Aleyas AG, Nautiyal B, et al. Nucleic Acid and Immunological Diagnostics for SARS-CoV-2: Processes, Platforms and Pitfalls. Diagnostics (Basel). 2020;10:866.

Public Health Agency of Canada. Public health management of cases and contacts associated with COVID-19. Updated December 23, 2020. Available at: https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/health-professionals/interim-guidance-cases-contacts.html. Accessed April 4, 2021.

Randolph HE, Barreiro LB. Herd immunity: understanding COVID-19. Immunity. 2020;52:737.

Robbiani DF, Gaebler C, Muecksch F, et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020;584:437-442.

Rostami A, Sepidarkish M, Leeflang MMG, et al. SARS-CoV-2 seroprevalence worldwide: a systematic review and meta-analysis. Clin Microbiol Infect. 2020;27:331-340.

Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med. 2020;382:970.

Russell FM, Ryan K, Snow K, et al. COVID-19 in Victorian Schools: an analysis of child-care and school outbreak data and evidence-based recommendations for opening schools and keeping them open. Melbourne, Australia: Murdoch Children’s Research Institute and the University of Melbourne; 25 September, 2020. Available at: https://www.dhhs.vic.gov.au/sites/default/files/documents/202009/Report-summary-COVID-19-in-victorian-schools-pdf.pdf. Accessed April 4, 2021.

US Food and Drug Administration. Coronavirus (COVID-19) update: FDA issues Emergency Use Authorization to Yale School of Public Health for SalivaDirect, which uses a new method of saliva sample processing. Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-yale-school-public-health. Accessed April 4, 2021.

Vogels CBV, Brackney DE, Wang J, et al. SalivaDirect: simple and sensitive molecular diagnostic test for SARS-CoV-2 surveillance. Available at: https://www.medrxiv.org/content/10.1101/2020.08.03.20167791v1.full.pdf. Accessed April 4, 2021. Note: This study has not been peer reviewed.

Volz EM, Hill V, McCrone JT, et al. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity. medRxiv. September 1, 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.07.31.20166082v2. Accessed April 4, 2021.

Wang Y, Zhang L, Sang L, et al. Kinetics of viral load and antibody response in relation to COVID-19 severity. J Clin Invest. 2020a;138759.

Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020b;323:1843-1844

Ward H, Cooke G, Atchison C, et al. Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults. medRxiv. October 27, 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.10.26.20219725v1. Accessed April 4, 2021.

Weekes M, Jones, NK, Rivett L, et al. Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection. Available at: https://www.authorea.com/users/332778/articles/509881-single-dose-bnt162b2-vaccine-protects-against-asymptomatic-sars-cov-2-infection?commit=3947109177a9e05258812c5566ab91f44c3e08e6. Accessed April 4, 2021. Note: This study has not been peer reviewed.

Woloshin S, Neeraj P, Kesselheim AS. False negative tests for SARS-CoV-2 infection—challenges and Implications. N Engl J Med. 2020;383:e38.

World Health Organization. Criteria for releasing COVID-19 patients from isolation: scientific brief. Available at: https://www.who.int/publications/i/item/criteria-for-releasing-covid-19-patients-from-isolation. Accessed April 4, 2021.

Xiao F, Sun J, Xu Y, et al. Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19. Emerg Infect Dis. 2020;26:1920-1922.

Yang Y, Yang M, Shen C, et al. Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections. medRxiv. 2020;[Preprint]. Note: This study has not been peer reviewed.

Young BE, Fong SW, Chan YH, et al. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. Lancet. 2020;396:603-611.

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