Diana Buitrago-Garcia , Dianne Egli-Gany , Michel J. Counotte , Stefanie Hossmann, Hira Imeri,
Aziz Mert Ipekci, Georgia Salanti, Nicola Low
There is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living systematic review and meta-analysis to address three questions: (1) Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? (3) What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection or presymptomatic?
There is ongoing discussion about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The authors of a narrative review report a range of proportions of participants positive for SARS-CoV-2 but asymptomatic in different studies from 6% to 96% . The discrepancy results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. The studies cited include both people who will remain asymptomatic throughout and those, known as presymptomatic, who will develop symptoms of coronavirus disease 2019 (COVID-19) if followed up . The full spectrum and distribution of COVID-19, from completely asymptomatic, to mild and nonspecific symptoms, viral pneumonia, respiratory distress syndrome, and death, are not yet known . Without follow-up, however, the proportions of asymptomatic and presymptomatic infections cannot be determined.
We conducted a living systematic review, a systematic review that provides an online summary of findings and is updated when relevant new evidence becomes available . The review follows a published protocol (https://osf.io/9ewys/), which describes in detail the methods used to speed up review tasks  and to assess relevant evidence rapidly during a public health emergency . The first two versions of the review have been published as preprints [7,8]. We report our findings according to the statement on preferred reporting items for systematic reviews and meta-analyses (S1 PRISMA Checklist) . Ethics committee review was not required for this study. Box 1 shows our definitions of symptoms, asymptomatic infection, and presymptomatic status. We use the term asymptomatic SARS-CoV-2 infection for people without symptoms of COVID-19 who remain asymptomatic throughout the course of infection. We use the term presymptomatic for people who do not have symptoms of COVID-19 when enrolled in a study but who develop symptoms during adequate follow-up.
Summary of main findings
The summary proportion of SARS-CoV-2 that is asymptomatic throughout the course of infection was estimated, across all study settings, to be 20% (95% CI 17%–25%, 79 studies), with a prediction interval of 3%–67%. In studies that identified SARS-CoV-2 infection through screening of defined populations, the proportion of asymptomatic infections was 31% (95% CI 26%–37%, 7 studies). In 31 studies reporting on people who are presymptomatic but who go on to develop symptoms, the results were too heterogeneous to combine. The secondary attack rate from asymptomatic infections may be lower than that from symptomatic infections (relative risk 0.35, 95% CI 0.1–1.27). Modelling studies estimated a wide range of the proportion of all SARS-CoV-2 infections that result from transmission from asymptomatic and presymptomatic individuals.
Citation: Buitrago-Garcia D, Egli-Gany D, Counotte MJ, Hossmann S, Imeri H, Ipekci AM, et al. (2020) Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. PLoS Med 17(9): e1003346. https://doi.org/10.1371/journal.pmed.1003346
Academic Editor: Nathan Ford, World Health Organization, SWITZERLAND
Received: June 11, 2020; Accepted: August 18, 2020; Published: September 22, 2020
Copyright: © 2020 Buitrago-Garcia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The file listing all included studies and files used for all analyses are available from the Harvard Dataverse database. https://doi.org/10.7910/DVN/TZFXYO, Harvard Dataverse, V2, UNF:6:nblmY3m4rXPJ/oD2d9Lo5A== [fileUNF].
Funding: Funding was received from the Swiss National Science Foundation (320030_176233, to NL), http://www.snf.ch/en/Pages/default.aspx; European Union Horizon 2020 research and innovation programme (101003688, to NL), https://ec.europa.eu/programmes/horizon2020/en; Swiss government excellence scholarship (2019.0774, to DB-G), https://www.sbfi.admin.ch/sbfi/en/home/education/scholarships-and-grants/swiss-government-excellence-scholarships.html; and the Swiss School of Public Health Global P3HS stipend (to DB-G), https://ssphplus.ch/en/globalp3hs/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: GS has participated in two scientific meetings for Merck and Biogen. NL is a member of the PLOS Medicine editorial board.
Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; CrI, credibility interval; E, number of secondary transmission events; F, female; GI, generation interval; IQR, interquartile range; M, male; NR, not reported; RT-PCR, reverse transcriptase PCR; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; USA, United States of America.