TY - JOUR
T1 - The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis
AU - Pascall, David J.
AU - Vink, Elen
AU - Blacow, Rachel
AU - Bulteel, Naomi
AU - Campbell, Alasdair
AU - Campbell, Robyn
AU - Clifford, Sarah
AU - Davis, Chris
AU - Filipe, Ana da Silva
AU - Sakka, Noha El
AU - Fjodorova, Ludmila
AU - Forrest, Ruth
AU - Goldstein, Emily
AU - Gunson, Rory
AU - Haughney, John
AU - Holden, Matthew T. G.
AU - Honour, Patrick
AU - Hughes, Joseph
AU - James, Edward
AU - Lewis, Tim
AU - Lycett, Samantha
AU - MacLean, Oscar
AU - McHugh, Martin
AU - Mollett, Guy
AU - Onishi, Yusuke
AU - Parcell, Ben
AU - Ray, Surajit
AU - Robertson, David L.
AU - Shabaan, Sharif
AU - Shepherd, James G.
AU - Smollett, Katherine
AU - Templeton, Kate
AU - Wastnedge, Elizabeth
AU - Wilkie, Craig
AU - Williams, Thomas
AU - Thomson, Emma C.
AU - Robson, Samuel C.
AU - Connor, Thomas R.
AU - Loman, Nicholas J.
AU - Golubchik, Tanya
AU - Martinez Nunez, Rocio T.
AU - Bonsall, David
AU - Rambaut, Andrew A.
AU - Snell, Luke B.
AU - O'Grady, Justin
AU - Dervisevic, Samir
AU - Mather, Alison E.
AU - Stanley, Rachael
AU - Davidson, Rose K.
AU - Rudder, Steven
AU - The COVID-19 Genomics UK (COG-UK) Consortium
N1 - Data Availability: Data cannot be shared publicly due to ethical constraints on data sharing because it contains sensitive patient data. As such, full data cannot be removed from the NHS GG&C SafeHaven, a trusted research environment without appropriate permissions. Aggregated data are available in the supplementary materials. The Safe Haven can be contacted for data access requests [email protected].
Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. Funding was also provided by UKRI through the JUNIPER consortium (MR/V038613/1). Sequencing, bioinformatics and statistical support was funded by the Medical Research Council (MRC) core awards for the MRC-University of Glasgow Centre for Virus Research (MC UU 1201412) and MRC Biostatistics Unit (MC UU 00002/11). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2023/4/13
Y1 - 2023/4/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85152598538&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0284187
DO - 10.1371/journal.pone.0284187
M3 - Article
C2 - 37053201
AN - SCOPUS:85152598538
VL - 18
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e0284187
ER -