Increased Risk of Severe COVID-19 in Hospitalized Patients With SARS-CoV-2 Variant of Concern Alpha Infection in France: A Multicentre Matched Cohort Study With Retrospective Data Collection

Background: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 is debated and has to be analyzed in different epidemiological situations. We report our analysis in France. Methods: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to patients infected by historical lineages. Participants were matched on age (+/- 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale >5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease (age, BMI and comorbidities) to compare the 2 groups.  Findings: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p=0.004). Infection by VOC Alpha was associated with a higher risk of severe COVID-19 (41.7% vs 38.5% - aOR=1.33 95% CI [1.03-1.72]). The rate of mortality was 24.0% vs 19.0% (aHR 1.21 95% CI [0.93-1.58]). Interpretation: Infection by the VOC Alpha was associated with a higher risk of severe COVID-19 during the third COVID-19 epidemic wave in France. Clinical Trial Registration Details: Registered on ClinicalTrials.gov (NCT04863547). Funding Information: The study was funded by the ANRS Maladies Infectieuses Emergentes. Declaration of Interests: DC reports HIV grants from Janssen (2017-2018, 2019-2020), personal fees from Janssen (2018) and Gilead (2018, 2020) for lectures on HIV outside the submitted work. CC reports personal fees from Janssen (2018), MSD (2019), Gilead (2018-2020), Theratechnologies (2020) and ViiV Healthcare (2018-2020). HC reports personal fees from MSD (2020) and ViiV Healthcare (2020) for lectures on HIV. GMB reports support for attending meetings and personal fees from BMS, MSD, Janssen, Sanofi, Pfizer and Gilead for lectures outside the submitted work. JP reports support for attending meetings and personal fees from Gilead, Pfizer and Eumedica Gilead for lectures. DD reports personal fees from Gilead, ViiV Healthcare and Janssen for participation on an advisory Board. Other authors declare that they have no competing interest. Ethics Approval Statement: The study was approved by the SPILF Ethics Committee.