What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate, serial interval, and asymptomatic infection

Abstract

Background Current SARS-CoV-2 containment measures rely on the capacity to control person-to-person viral transmission. Effective prioritization of these measures can be determined by understanding SARS-CoV-2 transmission dynamics. We conducted a systematic review and meta-analyses of three parameters: (i) secondary attack rate (SAR) in various settings, (ii) clinical onset serial interval (SI), and (iii) the proportion of asymptomatic infection. Methods and Findings We searched PubMed, medRxiv, and bioRxiv databases between January 1, 2020, and May 15, 2020, for articles describing SARS-CoV-2 attack rate, SI, and asymptomatic infection. Studies were included if they presented original data for estimating point estimates and 95% confidence intervals of the three parameters. Random effects models were constructed to pool SAR, mean SI, and asymptomatic proportion. Risk ratios were used to examine differences in transmission risk by setting, type of contact, and symptom status of the index case. Publication and related bias were assessed by funnel plots and Egger's meta-regression test for small-study effects. Our search strategy for SAR, SI, and asymptomatic infection identified 459, 572, and 1624 studies respectively. Of these, 20 studies met the inclusion criteria for SAR, 18 studies for SI, and 66 studies for asymptomatic infection. We estimated the pooled household SAR at 15.4% (95% CI: 12.2%, 18.7%) compared to 4.0% (95% CI: 2.8%, 5.2%) in non-household settings. We observed variation across settings; however, the small number of studies limited power to detect associations and sources of heterogeneity. SAR of symptomatic index cases is significantly higher than cases that were symptom-free at diagnosis (RR 2.55, 95% CI: 1.47, 4.45). Adults appear to be more susceptible to transmission than children (RR 1.40, 95% CI: 1.00, 1.96). The pooled mean SI is estimated at 4.87 days (95% CI: 3.98, 5.77). The pooled proportion of cases who had no symptoms at diagnosis is 25.9% (95% CI: 18.8%, 33.1%). Conclusions Based our pooled estimates, 10 infected symptomatic persons living with 100 contacts would result in 15 additional cases in <5 days. To be effective, quarantine of contacts should occur within 3 days of symptom onset. If testing and tracing relies on symptoms, one-quarter of cases would be missed. As such, while aggressive contact tracing strategies may be appropriate early in an outbreak, as it progresses, control measures should transition to account for SAR variability across settings. Targeted strategies focusing on high-density enclosed settings may be effective without overly restricting social movement.

Substantial underestimation of SARS-CoV-2 infection in the United States

“…The quantity P(S 0 | test+) is a function of other parameters P(S 1 | untested), α, β, meaning its distribution is entirely determined by those three parameters. However, we considered estimates of P(S 0 | test +) to be more reliable than those of P(test + |S 1 ) and P(test + | S 0 ) because P(S 0 | test +) has been estimated in numerous published studies, including some with more representative sampling 1,2,4,[42][43][44][45] . Thus, we used Bayesian melding to incorporate both sources of information into a joint (melded) distribution on P(S 0 | test +) and P(S 1 | test +) = 1 -P(S 0 | test +) 46 .…”

“…In these studies, it is possible that individuals who were asymptomatic at the time of testing developed symptoms later. A meta-analysis reported that 25.9% (95% CI: 18.8%, 33.1%) of individuals who tested positive were asymptomatic at the time of diagnosis (N = 25 studies) 45 , and a narrative review reported a similar range of estimates from 16 studies 44 . Though there were more studies to support this prior than for other priors, we chose not perform a meta-analysis to obtain the prior distribution due to limitations that affect the generalizability of the majority of these studies.…”

“…Though there were more studies to support this prior than for other priors, we chose not perform a meta-analysis to obtain the prior distribution due to limitations that affect the generalizability of the majority of these studies. These include very small sizes (nearly 31% in the meta-analysis 45 had a sample size ≤10) and enrollment of non-representative populations, such as pregnant women, employees at a specific location, travelers on cruise ships, and nursing home residents. A recent narrative review which included many of the same studies came to similar conclusions regarding the risks of pooling data for formal analysis 44 .…”

Implementation and validation of a pooling strategy for a sustainable screening campaign for the presence of SARS-CoV-2

“…Since various studies have highlighted the existence of asymptomatic virus carriers, screening campaigns aimed at identifying and isolating these subjects could substantially contribute to the achievement of these objectives. Defining the prevalence of asymptomatic subjects, the fraction that later develop symptoms, their viral load and their transmission potential are still under investigations [10][11][12][13][14][15] . However, some mathematical modelling studies hypothesized that asymptomatic subjects can be the major responsible for COVID-19 transmission 16,17 .…”

Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment

“…In fact, it is now known that the course of infection includes an incubation pre-symptomatic period, during which the patients shows no sign of disease but are still potentially infectious (likely to a lesser degree), after which some individuals progress to a symptomatic state, while others remain asymptomatic, but still potentially infectious [8]. This behavior has important consequence on how we model COVID-19's epidemiology and plan countermeasures.…”