Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis
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 experie...
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| Published in | PLoS medicine Vol. 17; no. 9; p. e1003346 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
01.09.2020
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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?
We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources.
The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed. |
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| AbstractList | The end of follow-up was defined as any of the following: virological cure, with one or more negative reverse transcriptase PCR (RT-PCR) test results; follow-up for 14 days or more after the last possible exposure to an index case; follow-up for 7 days or more after the first RT-PCR positive result.
The end of follow-up was defined as any of the following: virological cure, with one or more negative RT-PCR test results; follow-up for 14 days or more after the last possible exposure to an index case; follow-up for 7 days or more after the first RT-PCR positive result.
The primary outcomes for each review question were (1) proportion with asymptomatic SARS-CoV-2 infection who did not experience symptoms at all during follow-up; (2) proportion with SARS-CoV-2 infections who did not have symptoms at the time of testing but developed symptoms during follow-up; (3) estimated proportion (with uncertainty interval) of SARS-CoV-2 transmission accounted for by people who are asymptomatic or presymptomatic.
The adapted tool included items about inclusion criteria, measurement of asymptomatic status, follow-up of course of disease, and statistical analysis. The end of follow-up was defined as any of the following: virological cure, with one or more negative reverse transcriptase PCR (RT-PCR) test results; follow-up for 14 days or more after the last possible exposure to an index case; follow-up for 7 days or more after the first RT-PCR positive result. The end of follow-up was defined as any of the following: virological cure, with one or more negative RT-PCR test results; follow-up for 14 days or more after the last possible exposure to an index case; follow-up for 7 days or more after the first RT-PCR positive result. The primary outcomes for each review question were (1) proportion with asymptomatic SARS-CoV-2 infection who did not experience symptoms at all during follow-up; (2) proportion with SARS-CoV-2 infections who did not have symptoms at the time of testing but developed symptoms during follow-up; (3) estimated proportion (with uncertainty interval) of SARS-CoV-2 transmission accounted for by people who are asymptomatic or presymptomatic. The adapted tool included items about inclusion criteria, measurement of asymptomatic status, follow-up of course of disease, and statistical analysis. 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?BACKGROUNDThere 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?We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources.METHODS AND FINDINGSWe searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources.The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed.CONCLUSIONSThe findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed. 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? We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources. The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed. BackgroundThere 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?Methods and findingsWe searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources.ConclusionsThe findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed. Diana Buitrago-Garcia and co-workers present a systematic review and meta-analysis on asymptomatic SARS-CoV-2 infections. |
| Author | Buitrago-Garcia, Diana Hossmann, Stefanie Counotte, Michel J. Salanti, Georgia Imeri, Hira Ipekci, Aziz Mert Egli-Gany, Dianne Low, Nicola |
| AuthorAffiliation | World Health Organization, SWITZERLAND 2 Graduate School of Health Sciences, University of Bern, Bern, Switzerland 1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland |
| AuthorAffiliation_xml | – name: 2 Graduate School of Health Sciences, University of Bern, Bern, Switzerland – name: World Health Organization, SWITZERLAND – name: 1 Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland |
| Author_xml | – sequence: 1 givenname: Diana orcidid: 0000-0001-9761-206X surname: Buitrago-Garcia fullname: Buitrago-Garcia, Diana – sequence: 2 givenname: Dianne orcidid: 0000-0002-4725-0475 surname: Egli-Gany fullname: Egli-Gany, Dianne – sequence: 3 givenname: Michel J. orcidid: 0000-0003-1039-6873 surname: Counotte fullname: Counotte, Michel J. – sequence: 4 givenname: Stefanie orcidid: 0000-0003-1600-5925 surname: Hossmann fullname: Hossmann, Stefanie – sequence: 5 givenname: Hira orcidid: 0000-0002-0412-1649 surname: Imeri fullname: Imeri, Hira – sequence: 6 givenname: Aziz Mert orcidid: 0000-0002-0260-9691 surname: Ipekci fullname: Ipekci, Aziz Mert – sequence: 7 givenname: Georgia orcidid: 0000-0002-3830-8508 surname: Salanti fullname: Salanti, Georgia – sequence: 8 givenname: Nicola orcidid: 0000-0003-4817-8986 surname: Low fullname: Low, Nicola |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32960881$$D View this record in MEDLINE/PubMed |
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| Snippet | There is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living systematic... The end of follow-up was defined as any of the following: virological cure, with one or more negative reverse transcriptase PCR (RT-PCR) test results;... Diana Buitrago-Garcia and co-workers present a systematic review and meta-analysis on asymptomatic SARS-CoV-2 infections. BackgroundThere is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living... |
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| SubjectTerms | Application programming interface Asymptomatic Asymptomatic Diseases - epidemiology Asymptomatic Infections - epidemiology Betacoronavirus Bias Biology and life sciences Coronavirus Infections - epidemiology Coronavirus Infections - physiopathology Coronavirus Infections - transmission Coronaviruses COVID-19 Disease Progression Disease transmission Humans Infections Laboratories Mass Screening Medicine and health sciences Meta-analysis Pandemics People and Places Pneumonia, Viral - epidemiology Pneumonia, Viral - physiopathology Pneumonia, Viral - transmission Polymerase chain reaction Population Research and Analysis Methods Reverse Transcriptase Polymerase Chain Reaction RNA-directed DNA polymerase SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Statistical analysis Subject heading schemes Systematic review |
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| Title | Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis |
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