PMID- 35617363
OWN - NLM
STAT- MEDLINE
DCOM- 20220530
LR  - 20220716
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 19
IP  - 5
DP  - 2022 May
TI  - Occurrence and transmission potential of asymptomatic and presymptomatic 
      SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.
PG  - e1003987
LID - 10.1371/journal.pmed.1003987 [doi]
LID - e1003987
AB  - BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory 
      Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence 
      is increasing and study designs have changed over time. We updated a living 
      systematic review to address 3 questions: (1) Among people who become infected 
      with SARS-CoV-2, what proportion does not experience symptoms at all during their 
      infection? (2) What is the infectiousness of asymptomatic and presymptomatic, 
      compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of 
      SARS-CoV-2 transmission in a population is accounted for by people who are 
      asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first 
      published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, 
      Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, 
      most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, 
      which documented symptom status at the beginning and end of follow-up, or 
      mathematical modelling studies were included. Studies restricted to people 
      already diagnosed, of single individuals or families, or without sufficient 
      follow-up were excluded. 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 a bespoke checklist and modelling 
      studies with a published checklist. All data syntheses were done using random 
      effects models. Review question (1): We included 130 studies. Heterogeneity was 
      high so we did not estimate a mean proportion of asymptomatic infections overall 
      (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 
      studies based on screening of defined populations (IQR 20% to 65%, prediction 
      interval 4% to 94%). In 46 studies based on contact or outbreak investigations, 
      the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 
      25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of 
      people with asymptomatic infection compared with symptomatic infection was 0.32 
      (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 
      modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from 
      presymptomatic individuals was higher than from asymptomatic individuals. 
      Limitations of the evidence include high heterogeneity and high risks of 
      selection and information bias in studies that were not designed to measure 
      persistently asymptomatic infection, and limited information about variants of 
      concern or in people who have been vaccinated. CONCLUSIONS: Based on studies 
      published up to July 2021, most SARS-CoV-2 infections were not persistently 
      asymptomatic, and asymptomatic infections were less infectious than symptomatic 
      infections. Summary estimates from meta-analysis may be misleading when 
      variability between studies is extreme and prediction intervals should be 
      presented. Future studies should determine the asymptomatic proportion of 
      SARS-CoV-2 infections caused by variants of concern and in people with immunity 
      following vaccination or previous infection. Without prospective longitudinal 
      studies with methods that minimise selection and measurement biases, further 
      updates with the study types included in this living systematic review are 
      unlikely to be able to provide a reliable summary estimate of the proportion of 
      asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science 
      Framework (https://osf.io/9ewys/).
FAU - Buitrago-Garcia, Diana
AU  - Buitrago-Garcia D
AUID- ORCID: 0000-0001-9761-206X
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
AD  - Graduate School of Health Sciences, University of Bern, Bern, Switzerland.
FAU - Ipekci, Aziz Mert
AU  - Ipekci AM
AUID- ORCID: 0000-0002-0260-9691
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
FAU - Heron, Leonie
AU  - Heron L
AUID- ORCID: 0000-0002-3820-3343
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
FAU - Imeri, Hira
AU  - Imeri H
AUID- ORCID: 0000-0002-0412-1649
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
FAU - Araujo-Chaveron, Lucia
AU  - Araujo-Chaveron L
AUID- ORCID: 0000-0002-2110-6088
AD  - EHESP French School of Public Health, Paris and Rennes, France.
AD  - Institut Pasteur, Paris, France.
FAU - Arevalo-Rodriguez, Ingrid
AU  - Arevalo-Rodriguez I
AUID- ORCID: 0000-0002-7326-4504
AD  - Clinical Biostatistics Unit, Hospital Universitario Ramon y Cajal, IRYCIS, CIBER 
      of Epidemiology and Public Health, Madrid, Spain.
FAU - Ciapponi, Agustin
AU  - Ciapponi A
AUID- ORCID: 0000-0001-5142-6122
AD  - Instituto de Efectividad Clinica y Sanitaria (IECS-CONICET), Buenos Aires, 
      Argentina.
FAU - Cevik, Muge
AU  - Cevik M
AUID- ORCID: 0000-0003-1133-3874
AD  - Division of Infection and Global Health Research, School of Medicine, University 
      of St. Andrews, Fife, Scotland, United Kingdom.
FAU - Hauser, Anthony
AU  - Hauser A
AUID- ORCID: 0000-0002-7221-1929
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
FAU - Alam, Muhammad Irfanul
AU  - Alam MI
AUID- ORCID: 0000-0002-8759-6585
AD  - EHESP French School of Public Health, Paris and Rennes, France.
FAU - Meili, Kaspar
AU  - Meili K
AUID- ORCID: 0000-0002-9889-4406
AD  - Department of Epidemiology and Global Health, Umea University, Umea, Sweden.
FAU - Meyerowitz, Eric A
AU  - Meyerowitz EA
AUID- ORCID: 0000-0001-7954-6548
AD  - Division of Infectious Diseases, Montefiore Medical Center, Bronx, New York, New 
      York, United States of America.
FAU - Prajapati, Nirmala
AU  - Prajapati N
AUID- ORCID: 0000-0001-7518-5968
AD  - Universite Paris-Saclay, Paris, France.
FAU - Qiu, Xueting
AU  - Qiu X
AUID- ORCID: 0000-0001-6810-7304
AD  - Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH 
      Chan School of Public Health, Boston, Massachusetts, United States of America.
FAU - Richterman, Aaron
AU  - Richterman A
AUID- ORCID: 0000-0001-7920-7191
AD  - Division of Infectious Diseases, University of Pennsylvania, Philadelphia, 
      Pennsylvania, United States of America.
FAU - Robles-Rodriguez, William Gildardo
AU  - Robles-Rodriguez WG
AUID- ORCID: 0000-0002-8383-6844
AD  - Fundacion Universitaria de Ciencias de la Salud, Bogota, Colombia.
FAU - Thapa, Shabnam
AU  - Thapa S
AD  - Manchester Centre for Health Economics, University of Manchester, Manchester, 
      United Kingdom.
FAU - Zhelyazkov, Ivan
AU  - Zhelyazkov I
AUID- ORCID: 0000-0001-6320-7517
AD  - University of Sheffield, Sheffield, United Kingdom.
FAU - Salanti, Georgia
AU  - Salanti G
AUID- ORCID: 0000-0002-3830-8508
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
FAU - Low, Nicola
AU  - Low N
AUID- ORCID: 0000-0003-4817-8986
AD  - Institute of Social and Preventive Medicine, University of Bern, Bern, 
      Switzerland.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20220526
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
SB  - IM
MH  - Asymptomatic Infections/epidemiology
MH  - *COVID-19/epidemiology
MH  - Humans
MH  - Mass Screening
MH  - Prospective Studies
MH  - SARS-CoV-2
PMC - PMC9135333
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: NL is an academic editor at PLOS Medicine, 
      received the grant funding from the organisations declared above, is a member of 
      the Swiss National COVID-19 Science Task Force, and is on the scientific board of 
      Sefunda, a start-up company that develops point-of-care diagnostics for sexually 
      transmitted infections. DBG receives funding from the organisations declared 
      above. AMI, LH, HI receive salary support from the grants to NL from the Swiss 
      National Science Foundation 320030_176233, and/or European Union H2020 101003688
EDAT- 2022/05/27 06:00
MHDA- 2022/05/31 06:00
PMCR- 2022/05/26
CRDT- 2022/05/26 14:03
PHST- 2022/01/24 00:00 [received]
PHST- 2022/04/13 00:00 [accepted]
PHST- 2022/05/26 14:03 [entrez]
PHST- 2022/05/27 06:00 [pubmed]
PHST- 2022/05/31 06:00 [medline]
PHST- 2022/05/26 00:00 [pmc-release]
AID - PMEDICINE-D-22-00260 [pii]
AID - 10.1371/journal.pmed.1003987 [doi]
PST - epublish
SO  - PLoS Med. 2022 May 26;19(5):e1003987. doi: 10.1371/journal.pmed.1003987. 
      eCollection 2022 May.