Background The second coronavirus disease (COVID-19) epidemic wave in the UK progressed aggressively and was characterised by the emergence and circulation of variant of concern alpha (VOC 202012/01). The impact of this variant on in-hospital COVID-19-specific mortality has not been widely studied. We aimed to compare mortality, clinical characteristics, and management of COVID-19 patients across epidemic waves to better understand the progression of the epidemic at a hospital level and support resource planning. Methods We conducted an analytical, dynamic cohort study in a large hospital in South London. We included all adults (≥ 18 years) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission to COVID-19-specific wards between January 2020 and March 2021 ( n = 2701). Outcome was COVID-19-specific in-hospital mortality ascertained through Medical Certificate Cause of Death. Results In the second wave, the number of COVID-19 admissions doubled, and the crude mortality rate dropped 25% (1.66 versus 2.23 per 100 person-days in second and first wave, respectively). After accounting for age, sex, dexamethasone, oxygen requirements, symptoms at admission and Charlson Comorbidity Index, mortality hazard ratio associated with COVID-19 admissions was 1.62 (95% CI 1.26, 2.08) times higher in the second wave. Conclusions Although crude mortality rates dropped during the second wave, the multivariable analysis suggests a higher underlying risk of death for COVID-19 admissions in the second wave. These findings are ecologically correlated with an increased circulation of SARS-CoV-2 variant of concern 202012/1 (alpha). Availability of improved management, particularly dexamethasone, was important in reducing risk of death. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01719-1.
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