Objectives: To determine how the intrinsic severity of successively dominant SARS-CoV-2 variants changed over the course of the pandemic.

Methods: A retrospective cohort analysis in the NHS Greater Glasgow and Clyde (NHS GGC) Health Board. All sequenced non-nosocomial adult COVID-19 cases in NHS GGC with relevant SARS-CoV-2 lineages (B.1.177/Alpha, Alpha/Delta, AY.4.2 Delta/non-AY.4.2 Delta, non-AY.4.2 Delta/Omicron, and BA.1 Omicron/BA.2 Omicron) during analysis periods were included. Outcome measures were hospital admission, ICU admission, or death within 28 days of positive COVID-19 test. We report the cumulative odds ratio; the ratio of the odds that an individual experiences a severity event of a given level vs all lower severity levels for the resident and the replacement variant after adjustment.

Results: After adjustment for covariates, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177, 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha, 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta, 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta, and 0.86 (95% CI: 0.68-1.09) for BA.2 Omicron versus BA.1 Omicron.

Conclusions: The direction of change in intrinsic severity between successively emerging SARS-CoV-2 variants was inconsistent, reminding us that the intrinsic severity of future SARS-CoV-2 variants remains uncertain.


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Pascall, D., Vink, E., Blacow, R., Bulteel, N., Campbell, A., Campbell, R., Clifford, S., Davis, C., da Silva Filipe, A., El Sakka, N., Fjodorova, L., Forrest, R., Goldstein, E., Gunson, R., Haughney, J., Holden, M., Honour, P., Hughes, J., James, E., Lewis, T., MacLean, O., McHugh, M., Mollett, G., Nyberg, T., Onishi, Y., Parcell, B., Ray, S., Robertson, D., Seaman, S., Shabaan, S., Shepherd, J., Smollett, K., Templeton, K., Wastnedge, E., Wilkie, C., Williams, T., Thomson, E. & COVID-19 Genomics UK (COG-UK) consortium 2023, 'Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent', Journal of Infection. https://doi.org/10.1016/j.jinf.2023.05.019

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Last updated: 29 August 2023
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