Abstract

Background The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death.

Methods In this prospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced and analysed for the presence of Alpha variant defining mutations. We prospectively matched sequence data to clinical outcomes as the variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. Additionally, we calculated an estimate of the growth rate of Alpha variant-associated infections following its introduction into Scotland, using phylogenetic data.

Results The Alpha variant was responsible for a third wave of SARS-CoV-2 in Scotland, and rapidly replaced the previously dominant second wave lineage B.1.177 due to a significantly higher transmission rate (∼5 fold). Of 1475 patients, 364 were infected with Alpha/B.1.1.7, 1030 with B.1.177, and 81 with other lineages. Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus non-Alpha variant). Viral load was higher in Alpha variant samples than in non-Alpha variant samples as measured by cycle threshold (Ct) value (mean Ct change: −2.46, 95% CI: −4.22, −0.70).

Conclusions The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.

Rights

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. http://creativecommons.org/licenses/by/4.0/

Cite as

Pascall, D., Mollett, G., Vink, E., Shepherd, J., Williams, T., Wastnedge, E., Blacow, R., Hughes, J., Robertson, D., Lycett, S., Bulteel, N., Campbell, R., Campbell, A., Clifford, S., Davis, C., Da Silva Filipe, A., Fjodorova, L., Forrest, R., Goldstein, E., Gunson, R., Haughney, J., Holden, M., Honour, P., James, E., Lewis, T., McHugh, M., Onishi, Y., Parcell, B., Sakka, N., Shabaan, S., Smollett, K., Templeton, K., The COVID-19 Genomics UK (COG-UK) Consortium & Thomson, E. 2022, 'The SARS-CoV-2 Alpha variant caused increased clinical severity of disease in Scotland: a genomics-based prospective cohort analysis'. To be published in MedRxiv [Preprint]. Available at: https://doi.org/10.1101/2021.08.17.21260128

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Last updated: 01 October 2022
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