Ratio of asymptomatic COVID-19 cases among ascertained SARS-CoV-2 infections in different regions and population groups in 2020: a systematic review and meta-analysis including 130 123 infections from 241 studies

Abstract

IntroductionAsymptomatic infection of SARS-CoV-2 may lead to silent community transmission and compromise the COVID-19 pandemic control measures. We aimed to estimate the rate of asymptomatic COVID-19 from published studies and compare this rate among different regions and patient groups.MethodsIn this systematic review and meta-analysis, electronic databases including Medline, Embase, PubMed and three Chinese electronic databases (Chinese National Knowledge Infrastructure [CNKI], WanFang Data and China Science, and Technology Journal Database [VIP]) were searched for literature published from 1 November 2019 to 31 December 2020. Original investigations with sample size (or number of subjects) not less than five were included for further analyses. Subgroup analyses were conducted according to different study types, study periods, geographical regions and patient demographics. The STATA (V.14.0) command ‘metaprop’ was implemented to conduct a meta-analysis of the pooled rate estimates of asymptomatic infections with exact binomial and score test-based 95% confidence interval (CI).ResultsA total of 130 123 ascertained COVID-19 infections from 241 studies were included in this meta-analysis, including 31 411 asymptomatic infections. The overall rate of asymptomatic infections was 23.6% (18.5%–29.1%) and 21.7% (16.8%–27.0%) before and after excluding presymptomatic cases, respectively. Subgroup analysis showed that significantly higher in pregnant women (48.8%, 28.9%–68.9%), children (32.1%, 24.2%–40.5%), and studies reporting screening programmes (36.0%, 24.6%–48.1%) conducted on or after 1 March 2020 (42.5%, 33.4%–51.9%). In terms of geographical region, the rate was the highest in Africa (64.3%, 56.7%–71.6%), followed by America (40.0%, 27.4%–53.3%), Europe (28.1%, 19.0%–38.1%) and Asia (18.1%, 13.2%–23.5%).ConclusionWe approximated that one-fifth of COVID-19 infections are asymptomatic throughout the course of infection. Public health policies targeting these high-risk groups may be recommended to achieve early identification and more stringent containment of the pandemic.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: update of a living systematic review and meta-analysis

“…Estimates from meta-analysis might be precise, but are likely to be unreliable owing to unacceptably high levels of heterogeneity. In three large systematic reviews, overall estimates had narrow confidence intervals [14-16], but I 2 values were 94-99% and prediction intervals, which show the extent of all between-study variability were not reported [17]. The prediction intervals that we calculated extended more or less from zero to 100% (S2 Appendix), making differences in estimates between these studies hard to interpret.…”

“…The number of published studies about SARS-CoV-2 is also increasing continuously and the types of published studies are also changing [10], including the designs of studies about asymptomatic infection. In systematic reviews of studies published to April 2021, reported point estimates from random effects meta-analysis models range from 17 to 41% [11][12][13][14][15][16]. Authors of these reviews typically report values of the I 2 statistic >90 [17,18], but heterogeneity is often not explored in detail and prediction intervals, which give information about sampling error and variability between studies, are recommended but rarely reported [17,19,20].…”

“…We used meta-regression for posthoc analyses examining associations with study size and publication date. To compare our findings with other studies, we extracted the raw data from five systematic reviews [11,[13][14][15][16] and calculated prediction intervals [17]. For review question 2, as a measure of infectiousness, we calculated the secondary attack rate as the number of SARS-CoV-2-infected contacts as a proportion of all close contacts ascertained.…”

“…Table 2 shows analyses for factors pre-specified in the protocol and post-hoc ( not appear to influence the estimated asymptomatic proportion. In three systematic reviews that we reanalysed, prediction intervals were: 1-83% (241 studies [14]); 4-97% (95 studies [15]); and 3-89% (170 studies [16]). I 2 values were between 94% and 99% (S2 Appendix).…”

Multi-Level Immune Support by Vitamins C and D during the SARS-CoV-2 Pandemic

“…In the absence of specific comorbidities that increase the risk of developing severe COVID-19 [ 23 ], infection with SARS-CoV-2 can be relatively mild and even asymptomatic [ 24 ]. To date, one published trial has investigated the effects of vitamin C supplementation on SARS-CoV-2 symptoms [ 25 ].…”