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. 2023 Aug;87(2):128-135.
doi: 10.1016/j.jinf.2023.05.019. Epub 2023 Jun 1.

Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent

David J Pascall  1 , Elen Vink  2 , Rachel Blacow  3 , Naomi Bulteel  4 , Alasdair Campbell  5 , Robyn Campbell  6 , Sarah Clifford  7 , Chris Davis  8 , Ana da Silva Filipe  9 , Noha El Sakka  10 , Ludmila Fjodorova  11 , Ruth Forrest  12 , Emily Goldstein  13 , Rory Gunson  14 , John Haughney  15 , Matthew T G Holden  16 , Patrick Honour  17 , Joseph Hughes  18 , Edward James  19 , Tim Lewis  20 , Oscar MacLean  21 , Martin McHugh  22 , Guy Mollett  23 , Tommy Nyberg  24 , Yusuke Onishi  25 , Ben Parcell  26 , Surajit Ray  27 , David L Robertson  28 , Shaun R Seaman  29 , Sharif Shabaan  30 , James G Shepherd  31 , Katherine Smollett  32 , Kate Templeton  33 , Elizabeth Wastnedge  34 , Craig Wilkie  35 , Thomas Williams  36 ; COVID-19 Genomics UK (COG-UK) Consortium; Emma C Thomson  37
Affiliations

Directions of change in intrinsic case severity across successive SARS-CoV-2 variant waves have been inconsistent

David J Pascall et al. J Infect. 2023 Aug.

Abstract

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.

Keywords: Alpha variant; COVID-19; Delta variant; Intrinsic severity; Omicron variant; SARS-CoV-2.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas C Williams is Principal Investigator for the BronchStart project, which is funded by the Respiratory Syncytial Virus Consortium in Europe (RESCEU), with data collection supported by the National Institute for Health Research.

Figures

Fig. 1
Fig. 1
SARS-CoV-2 sequencing through time in Scotland.
Fig. 2
Fig. 2
Comparison of case severity by age between pairs of co-circulating SARS-CoV-2 lineages Clinical severity was measured on a four-level ordinal scale based on observed outcomes within 28 days of a positive test: no hospitalisation, hospitalisation, admission to Intensive Care Unit/High Dependency Unit (ICU/HDU), death. The first column compares B.1.177 and Alpha between 1st November 2020 and 30th January 2021. The second column compares Alpha and Delta between 1st April 2021 and 30th June 2021. The third column compares Delta lineages against AY.4.2 between 1st July 2021 and 30th September 2021. The fourth column compares non-AY.4.2 Delta and Omicron between 1st December 2021 and 31st December 2021. The final column compares BA.1 Omicron and BA.2 Omicron between 1st January 2022 and 31st March 2022.
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