The SARS-CoV-2 Alpha variant causes increased clinical severity of disease

David J Pascall*, Guy Mollett, Rachel Blacow,, Naomi Bulteel, Robyn Campbell, Alasdair Campbell, Sarah Clifford, Chris Davis, Ana Da Silva Filipe, Ludmila Fjodorova, Ruth Forrester, Emily Goldstein, Rory Gunson, John Haughney, Matthew T.G. Holden, Patrick Honour, Joseph Hughes, Edward James, Tim Lewis, Samantha LycettMartin McHugh, Yusuke Onishi, Ben Parcell, David L Robertson, Noha El Sakka, Sharif Shabaan, James G. Shepherd, Katherine Smollett

*Corresponding author for this work

Research output: Working paper

Abstract / Description of output

Background The B.1.1.7 (Alpha) SARS-CoV-2 variant of concern was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between the B.1.1.7 lineage infection and increased 28-day mortality. However, to date none have addressed the impact of infection on severity of illness or the need for oxygen or ventilation.

Methods In this prospective clinical cohort sub-study of the COG-UK consortium, 1475 samples from hospitalised and community cases collected between the 1st November 2020 and 30th January 2021 were collected. These samples were sequenced in local laboratories and analysed for the presence of B.1.1.7-defining mutations. We prospectively matched sequence data to clinical outcomes as the lineage became dominant in Scotland and modelled the association between B.1.1.7 infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no support, 2. oxygen, 3. ventilation and 4. death. Additionally, we calculated an estimate of the growth rate of B.1.1.7-associated infections following introduction into Scotland using phylogenetic data.

Results B.1.1.7 was responsible for a third wave of SARS-CoV-2 in Scotland, and rapidly replaced the previously dominant second wave lineage B.1.177) due to a significantly higher transmission rate (∼5 fold). Of 1475 patients, 364 were infected with B.1.1.7, 1030 with B.1.177 and 81 with other lineages. 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 (B.1.1.7 versus non-B.1.1.7). Viral load was higher in B.1.1.7 samples than in non-B.1.1.7 samples as measured by cycle threshold (Ct) value (mean Ct change: -2.46, 95% CI: -4.22, -0.70).

Conclusions The B.1.1.7 lineage was associated with more severe clinical disease in Scottish patients than co-circulating lineages.
Original languageEnglish
Publication statusE-pub ahead of print - 24 Aug 2021

Publication series

Publishercold spring harbor


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