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Estimating infectiousness throughout SARS-CoV-2 infection course

Our take —

This study was conducted among 25,381 individuals with SARS-CoV-2 in Germany to estimate the infectiousness of the virus through its infection time course. Infectiousness was based on measurements of viral load and the probability of a sample yielding replicating SARS-CoV-2 in cell culture. Though the trajectory of viral load levels varied by individual and symptom severity, the overall time from a near-zero culture probability to the peak culture probability was 1.8 days, with peak viral load being one to three days before symptom onset. Compared to infection with non-B.1.1.7 (Alpha) variants, people infected with the Alpha variant had 10 times higher viral load and 2.6 times higher probability of yielding replicating virus in cell culture. Very high viral loads (more than 10^9 virus copies per swab) were detected in less than 10% of individuals, with one third of these higher viral loads among pre-symptomatic, asymptomatic, or mildly symptomatic infections. Findings also demonstrated that younger individuals had slightly lower viral loads at first positive PCR and peak culture probability compared to adults, which may have been due to differences in swab size or test timing.  This study allowed researchers to compare infectiousness proxy parameters across several characteristics (e.g. across time, by variant, by symptom severity, and by age), however, it should be noted that viral load and replicating virus are not direct measures of infectiousness.

Study design

Case Series

Study population and setting

The goals of this study were to better quantify viral infection and shedding of SARS-CoV-2, by measuring and comparing viral load (viral RNA concentration) and replicating virus isolated in cell culture. Specifically, the study aimed to estimate: 1) differences in infectiousness by age and gender, along with differences by symptom severity (e.g. pre-symptomatic, asymptomatic, symptomatic); 2) differences in infectiousness by viral variants (specifically B.1.1.7); and 3) timing and peak of infectiousness. Samples on 25,381 German individuals with at least one positive RT-PCT test from February 24, 2020 to April 2, 2021 were examined. Samples were divided into three categories: hospitalized (n=9519, 37.5%), pre-symptomatic, asymptomatic, or mildly symptomatic (PAMS) individuals receiving testing at walk-in community testing centers (n=6110, 24.1%), and other (n=9752, 38.4%). A total of 1,533 individuals had the B.1.1.7 variant. Viral loads were assessed using standard RT-PCR methodologies. The probability of viral culture was estimated using Baysesian regression by combining the estimated viral loads with cell culture isolation data from previously published work relating viral loads and culture probabilities. B.1.1.7 variants were identified using sequencing and comparisons were made using data from only testing centers that specifically reported B.1.1.7 cases.

Summary of Main Findings

Younger individuals had a lower mean log10 viral load than adults (those 20-65 years old) (0.5 lower for 0-5 year olds and 0.18 lower for older adolescents (those 15-20 years old)). Younger individuals also experienced 78% of the peak cell culture replication probability compared with older individuals, though the authors suggest this may have been due to a small swab size used for the youngest individuals in the sample. No differences were seen by gender. Very high viral loads (above 109 copies per swab) were detected in 8% of all individuals, with approximately one third of these high viral loads among presymptomatic, asymptomatic, or mildly symptomatic individuals. When comparing those with the B.1.1.7 variant with those without it, it was found that those with the B.1.1.7 variant had a higher mean log10 viral load (1.05 log10 higher), and a 2.6 times higher estimated cell culture replication probability. The estimated time from the start of viral shedding to peak viral load was 4.3 days.

Study Strengths

This study utilized multiple samples from individuals, and therefore it was possible to model viral dynamics over the time course of infection. Additionally, the large and generally varied population, by symptom severity, age, hospitalization, and variants allowed for the estimation of infectiousness parameters by a number of different characteristics.

Limitations

The authors note that the two parameters studied here: viral load and replicating virus isolate are not a direct measure of infectiousness, as behavior and context play an important role in infectiousness as well and these were not measured. Additionally, replicating virus was not measured in any of these samples, but instead relied on prior data to model culture positive probability. This analysis relies on the assumption that this prior work may be generalized to this study population.

Value added

This study furthers our understanding of SARS-CoV-2 infectiousness through the analysis of viral load, cell culture isolation, and genome sequencing data, especially to understand differences in infectiousness among those who are not symptomatic compared to those who are and those with the B.1.1.7 variant compared to others.

This review was posted on: 30 July 2021