The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis

• DOI: 10.1371/journal.pone.0284187
• Publication Date: 2023-04-13T17:48:20Z
• Authors: David J. Pascall; Elen Vink; Rachel Blacow; Naomi Bulteel; Alasdair Campbell; Robyn Campbell; Sarah Clifford; Chris Davis; Ana da Silva Filipe; Noha El Sakka; Ludmila Fjodorova; Ruth Forrest; Emily Goldstein; Rory Gunson; John Haughney; Matthew T. G. Holden; Patrick Honour; Joseph Hughes; Edward James; Tim Lewis; Samantha Lycett; Oscar MacLean; Martin McHugh; Guy Mollett; Yusuke Onishi; Ben Parcell; Surajit Ray; David L. Robertson; Sharif Shabaan; James G. Shepherd; Katherine Smollett; Kate Templeton; Elizabeth Wastnedge; Craig Wilkie; Thomas Williams; Emma C. Thomson
• Keywords: FOS: Computer and information sciences; 0301 basic medicine; Scotland/epidemiology; Science; 610; FOS: Physical sciences; E-DAS; 03 medical and health sciences; name=General; SDG 3 - Good Health and Well-being; RA0421; SARS-CoV-2/genetics; RA0421 Public health. Hygiene. Preventive Medicine; /dk/atira/pure/subjectarea/asjc/1000; 616; Humans; Retrospective Studies; MCC; Medicine and health sciences; Computer and information sciences; Biology and life sciences; SARS-CoV-2; Q; R; COVID-19; Genomics; 3. Good health; Physical sciences; Scotland; Medicine; People and places; Research Article

Objectives 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. We aimed to do this.

Methods In 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 Alpha 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.

Results 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 pre-Alpha variants).

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