Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.Author summary: The SARS-CoV-2 epidemic in the United Kingdom (UK) has been characterized by the successive transmission of distinct viral variants. Viral variation can impact viral properties, including infectiousness and pathogenicity. These properties may be linked to the amount of virus present in an infected individual. In this study, we examined the association between intra-patient viral burden and a range of factors, including viral variant, using a large, population-representative SARS-CoV-2 survey conducted in the UK. As part of our investigation, we developed a novel method to account for bias in sampled viral burden resulting from the study’s sampling methodology. Our findings indicate that viral burden within the host increases with age, is reduced by vaccination, and is influenced by the interplay between vaccination status and viral variant.