The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis
Pascall DJ., Vink E., Blacow R., Bulteel N., Campbell A., Campbell R., Clifford S., Davis C., Filipe ADS., Sakka NE., Fjodorova L., Forrest R., Goldstein E., Gunson R., Haughney J., Holden MTG., Honour P., Hughes J., James E., Lewis T., Lycett S., MacLean O., McHugh M., Mollett G., Onishi Y., Parcell B., Ray S., Robertson DL., Shabaan S., Shepherd JG., Smollett K., Templeton K., Wastnedge E., Wilkie C., Williams T., Thomson EC., Robson SC., Connor TR., Loman NJ., Golubchik T., Martinez Nunez RT., Bonsall D., Rambaut AA., Snell LB., Livett R., Ludden C., Corden S., Nastouli E., Nebbia G., Johnston I., Lythgoe KK., Torok ME., Goodfellow IG., Prieto JA., Saeed K., Jackson DK., Houlihan C., Frampton D., Hamilton WL., Witney AA., Bucca G., Pope CF., Moore C., Cutino-Moguel T., Harrison EM., Smith CP., Rogan F., Beckwith SM., Murray A., Singleton D., Eastick K., Sheridan LA., Randell P., Jackson LM., Ariani CV., Gonçalves S., Fairley DJ., Loose MW., Watkins J., Moses S., Nicholls S., Bull M., Amato R., Smith DL., Aanensen DM., Barrett JC., Kele B., Aggarwal D., Curran MD., Parmar S., Parker MD., Williams C., Glaysher S., Underwood AP., Bashton M., Pacchiarini N., Loveson KF., Byott M., Carabelli AM., Templeton KE.
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. :