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ObjectiveTo determine how the severity of successively dominant SARS-CoV-2 variants changed over the course of the COVID-19 pandemic. DesignRetrospective cohort analysis. SettingCommunity- and hospital-sequenced COVID-19 cases in the NHS Greater Glasgow and Clyde (NHS GG&C) Health Board. ParticipantsAll sequenced non-nosocomial adult COVID-19 cases in NHS GG&C infected with the relevant SARS-CoV-2 lineages during analysis periods. B.1.177/Alpha: 1st November 2020 - 30th January 2021 (n = 1640). Alpha/Delta: 1st April - 30th June 2021 (n = 5552). AY.4.2 Delta/non-AY.4.2 Delta: 1st July - 31st October 2021 (n = 9613). Non-AY.4.2 Delta/Omicron: 1st - 31st December 2021 (n = 3858). Main outcome measuresAdmission to hospital, ICU, or death within 28 days of positive COVID-19 test ResultsFor B.1.177/Alpha, 300 of 807 B.1.177 cases were recorded as hospitalised or worse, compared to 232 of 833 Alpha cases. After adjustment, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177. For Alpha/Delta, 113 of 2104 Alpha cases were recorded as hospitalised or worse, compared to 230 of 3448 Delta cases. After adjustment, the cumulative odds ratio was 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha. For non-AY.4.2 Delta/AY.4.2 Delta, 845 of 8644 non-AY.4.2 Delta cases were recorded as hospitalised or worse, compared to 101 of 969 AY.4.2 Delta cases. After adjustment, the cumulative odds ratio was 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta. For non-AY.4.2 Delta/Omicron, 30 of 1164 non-AY.4.2 Delta cases were recorded as hospitalised or worse, compared to 26 of 2694 Omicron cases. After adjustment, the median cumulative odds ratio was 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta. ConclusionsThe direction of change in disease severity between successively emerging SARS-CoV-2 variants of concern was inconsistent. This heterogeneity demonstrates that severity associated with future SARS-CoV-2 variants is unpredictable.
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ObjectivesThe 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. We aimed to do this. MethodsIn this retrospective 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. We 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. ResultsOur 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). ConclusionsThe Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.
