Abstract
Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). We included all positive nose and throat swabs 26 April 2020 to 13 March 2021 from the UK's national COVID-19 Infection Survey, tested by RT-PCR for the N, S, and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Of 3,312,159 nose and throat swabs, 27,902 (0.83%) were RT-PCR-positive, 10,317 (37%), 11,012 (40%), and 6550 (23%) for 3, 2, or 1 of the N, S, and ORF1ab genes, respectively, with median Ct = 29.2 (~215 copies/ml; IQR Ct = 21.9-32.8, 14-56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity, and age. Single-gene positives almost invariably had Ct > 30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4808 (78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody negative. Marked variation in community SARS-CoV-2 Ct values suggests that they could be a useful epidemiological early-warning indicator. Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.
Highlights
After initial reductions in SARS-CoV-2 cases in mid-2020, following release of large-scale lockdowns (Flaxman et al, 2020), infection rates have undergone waves of resurgence and suppression in many countries worldwide
A small number of participants appeared to have become infected despite antecedent high anti-spike antibody titres, one case in particular which had ‘higher evidence’ positive swab tests separated by four consecutive negative swabs with 65 days between positive swabs. In this large community surveillance study, we found wide variation in cycle threshold (Ct) values
Whilst Ct values were independently associated with several factors, including symptoms at/ around the test as previously reported (Edwards et al, 2020; Lee et al, 2020), their effects were small compared with population-level variability
Summary
After initial reductions in SARS-CoV-2 cases in mid-2020, following release of large-scale lockdowns (Flaxman et al, 2020), infection rates have undergone waves of resurgence and suppression in many countries worldwide. Estimates of asymptomatic infection rates vary, being 17–41% overall in recent reviews (Buitrago-Garcia et al, 2020; Byambasuren et al, 2020), but these included many studies of contacts of confirmed cases. Studies have generally indicated lower rates of transmission from asymptomatic infection (Buitrago-Garcia et al, 2020; Byambasuren et al, 2020), this may be a proxy for SARS-CoV-2 viral load as a key determinant of transmission. Most studies rely on ‘average’ estimates of the asymptomatic infection percentage, independent of characteristics and viral load, and have not quantified temporal variation in these key parameters for mathematical models across the community. Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity, and age.
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