Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
Walker AS., Pritchard E., House T., Robotham JV., Birrell PJ., Bell I., Bell JI., Newton JN., Farrar J., Diamond I., Studley R., Hay J., Vihta K-D., Peto TEA., Stoesser N., Matthews PC., Eyre DW., Pouwels KB.
<jats:sec id="abs1"><jats:title>Background:</jats:title><jats:p>Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load).</jats:p></jats:sec><jats:sec id="abs2"><jats:title>Methods:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="abs3"><jats:title>Results:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="abs4"><jats:title>Conclusions:</jats:title><jats:p>Marked variation in community SARS-CoV-2 Ct values suggests that they could be a useful epidemiological early-warning indicator.</jats:p></jats:sec><jats:sec id="abs5"><jats:title>Funding:</jats:title><jats:p>Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.</jats:p></jats:sec>