In a recent study published in PLOS Pathogens, researchers assessed the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on host viral burden.

Study: 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. Image Credit: Andrii Vodolazhskyi/Shutterstock.comStudy: 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. Image Credit: Andrii Vodolazhskyi/


In the United Kingdom (UK), the coronavirus disease 2019 (COVID-19) epidemic has been characterized by distinct SARS-CoV-2 variants. The Alpha, Delta, and Omicron variants exhibit substantial transmission advantages over previous variants.

The underlying cause may include differences in the infectious period, host viral burden, or per-virion transmission probability between hosts.

The study and findings

In the present study, researchers investigated the associations between SARS-CoV-2 variants and host viral burden using data from the UK’s COVID-19 infection survey (CIS). In CIS, private households were randomly selected from previous surveys and address lists to constitute a nationally representative sample.

Participants provided self-collected throat and nose swabs and information about demographics, close contacts, symptoms, and relevant behaviors. Subjects aged ≥ 16 from some households were asked to provide blood samples for serologic analyses.

Reverse-transcription polymerase chain reaction (RT-PCR) was performed, and the cycle threshold (Ct) values were recorded. Sequencing was attempted on all samples with a Ct ≤ 30 from December 2020.

Sequencing was performed at the Universities of Oxford and Northumbria for samples collected between September 2020 and July 2021 and September 2021 and January 2022, respectively.

Samples at Oxford covered parts of B.1.177, Alpha, and Delta waves, whereas those sequenced at Northumbria covered aspects of Delta and Omicron (BA.1) waves. Blood samples were tested for anti-SARS-CoV-2 antibodies.

The researchers developed a framework to assess the association between SARS-CoV-2 variants and viral burden by adjusting observed Ct values to account for distinct epidemiologic trajectories of the variants. This epidemiologic adjustment was applied to Alpha variant samples from non-vaccinated subjects without prior SARS-CoV-2 exposure.

The researchers split samples into early and late phases of the Alpha wave. Early-phase samples had lower median unadjusted Ct values than late-phase samples—the average time since infection was longer in the late phase relative to the early phase.

After adjustment, Ct values of early Alpha wave samples increased, whereas those of late-phase samples decreased. Moreover, the distribution of adjusted Ct values from both phases seemed more closely aligned than unadjusted Ct values.

In comparison, the adjustment applied to the entire set of samples from the Alpha wave was negligible. Next, the team used partial least squares regression to determine the association of sex, age, sampling date, ethnicity, first vaccine product, healthcare worker status, and prior SARS-CoV-2 exposure with adjusted Ct values.

Sampling date and age were predictors of Ct values for samples sequenced at both locations. Sex, ethnicity, and healthcare worker status were not associated with the viral burden. Among non-vaccinated individuals without prior SARS-CoV-2 exposure, Ct values were higher for B.1.177 than Alpha infections, corresponding to a 44% lower viral load.

Ct values were similar for Alpha and Delta variants but lower for Omicron BA.1 than Delta. Moreover, samples from vaccinated individuals had higher Ct values than those without SARS-CoV-2 exposure, translating into a 67% decline in viral burden upon vaccination.

The effect of two or more vaccine doses was insignificant, but the impact of the variant was considerable among vaccinated subjects.

Lower Ct values were observed for Delta samples compared to Alpha samples, suggesting that the viral burden was 286% higher for Delta than Alpha infections.

Further, reduced Ct values were also observed for the Omicron BA.1 variant compared to the Delta variant and among ChAdOx1 vaccinees relative to BNT162b2 recipients.


The study introduced a framework for comparing host viral burden across SARS-CoV-2 variants. The researchers inferred (adjusted) Ct values from large-scale survey data and observed temporal shifts in viral burden with changes in population immunity. Specifically, viral burden reduced over time but increased with age.

The viral burden was about 115% increased for Alpha infections than B.1.177 among individuals without prior SARS-CoV-2 exposure.

Notably, viral burden was reduced with vaccination; nevertheless, it was 286% higher for Delta than Alpha infections, presumably due to the higher genetic difference between the vaccine strain and the Delta variant than SARS-CoV-2 Alpha.

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