Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future

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

Objective

To determine how the severity of successively dominant SARS-CoV-2 variants changed over the course of the COVID-19 pandemic.

Design

Retrospective cohort analysis.

Setting

Community- and hospital-sequenced COVID-19 cases in the NHS Greater Glasgow and Clyde (NHS GG&C) Health Board.

Participants

All 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 measures

Admission to hospital, ICU, or death within 28 days of positive COVID-19 test

Results

For 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.

Conclusions

The 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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