SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of observational studies and trials reporting viral shedding kinetics.
PubMed 33521734 · doi:10.1016/S2666-5247(20)30172-5
What was done
The authors conducted a systematic review and meta-analysis of MEDLINE, Embase, Europe PubMed Central, medRxiv, bioRxiv, and grey literature from Jan 1, 2003, to June 6, 2020. They included case series (≥5 participants), cohort studies, and randomised controlled trials reporting viral load kinetics, duration of viral RNA shedding, or viable virus detection for SARS-CoV-2, SARS-CoV, or MERS-CoV. Quality was assessed using Joanna Briggs Institute appraisal tools. Mean duration of shedding was pooled using random-effects meta-analysis, and moderators were assessed using weighted meta-regression.
What was found
The review identified 79 studies (5,340 individuals) on SARS-CoV-2, 8 studies (1,858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV. - Mean duration of SARS-CoV-2 RNA shedding was 17.0 days (95% CI 15.5–18.6; 43 studies, 3,229 individuals) in the upper respiratory tract, 14.6 days (95% CI 9.3–20.0; 7 studies, 260 individuals) in the lower respiratory tract, 17.2 days (95% CI 14.4–20.1; 13 studies, 586 individuals) in stool, and 16.6 days (95% CI 3.6–29.7; 2 studies, 108 individuals) in serum. - Maximum shedding duration reached 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. - Mean SARS-CoV-2 shedding duration correlated positively with age (slope 0.304 [95% CI 0.115–0.493]; p=0.0016). - SARS-CoV-2 upper respiratory viral load peaked within the first week of illness (compared with days 10–14 for SARS-CoV and days 7–10 for MERS-CoV). - No study detected live, replication-competent virus beyond day 9 of illness, despite persistent high RNA loads.
Why it matters
This study demonstrates that SARS-CoV-2 infectiousness peaks early in the first week of illness, explaining rapid community spread, and that viable virus shedding ceases by day 9 despite prolonged PCR positivity. These findings provide strong empirical justification for symptom-onset-based isolation durations.
Limits
The search captured literature only through June 2020, representing early wild-type SARS-CoV-2 in immunologically naive populations. Most included designs were observational cohorts or case series with heterogeneous sampling schedules. Fewer studies performed viral culture than RT-PCR, and culture sensitivity limitations might influence the observed day 9 cutoff.
Cited by
- supports In COVID-19 cases, death typically occurs days after the infectious transmission window has already passed.