SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

Abstract

Background Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. Methods In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. Findings 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17•0 days (95% CI 15•5-18•6; 43 studies, 3229 individuals) in upper respiratory tract, 14•6 days (9•3-20•0; seven studies, 260 individuals) in lower respiratory tract, 17•2 days (14•4-20•1; 13 studies, 586 individuals) in stool, and 16•6 days (3•6-29•7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0•304 [95% CI 0•115-0•493]; p=0•0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10. Interpretation Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. Funding None.

Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study

“…The timing of the peak Ct was sampled from the incubation period (time from exposure to onset of symptoms) using the pooled log-normal distribution from a published meta-analysis. 10 The peak Ct value is normally distributed with mean 22·3 and SD of 4·2 9 and the time of cessation of viral shedding, a return to baseline, is parameterised as normally distributed with mean 17 days after exposure and SD of 0·94 days for symptomatic individuals, 11 with asymptomatic individuals having a duration that is 40% shorter. 10 The peak and end times are drawn, for each individual, in such a way that each individual is at the same quantile, q, in the cumulative densities of each distribution; this guarantees that the ordering of peak and end is maintained and that there are no rapid returns to baseline Ct after a slow transition to peak Ct. We then fit a cubic Hermite spline 12 to the generated exposure, peak, and end values for each individual, constraining the slope of the curve to be zero at each of them, to simulate viral load kinetics (in Ct) over the course of infection.…”

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial

“…Before considering higher or multiple dose schemes, there is also need to better understand the potential role of ivermectin´s metabolites in any observed effect. Finally, given the tendency to lower IgG titers in the ivermectin group, there is need to evaluate the potential relationship between ivermectin treatment, disease severity, inflammation, viral dynamics and antibody titers; [ 37 , 38 ] particular attention should be paid to the long-term humoral and cellular immune responses against SARS-CoV-2 in ivermectin treated patients.…”

Performance of a Point-of-Care Test for the Rapid Detection of SARS-CoV-2 Antigen

“…The diagnosis of a SARS-CoV-2 infection would therefore be too uncertain for a medical laboratory based on the antigen detection alone. However, it is known that patients have a high viral load in their URT in the first days of infection [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Thus, POCT for the detection of SARS-CoV-2 antigen may reliably identify patients in this period who can then be isolated to prevent further spreading of infection [ 9 , 10 , 11 , 12 , 14 , 29 ].…”

“…A recent review emphasizes that virus growth rate correlates with viral load. In addition, the authors report that with a few exceptions, cultivation is only successful within the first nine days after the onset of the disease, even if some patients have a high viral load in the RT-PCR for weeks [ 28 ]. This could explain why no virus could be isolated in some of the highly positive samples in our study, especially since we have no information on the onset and kind of symptoms.…”