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A recent study by Kang and colleagues (1) found that individuals infected with the SARS-CoV-2 BA.5 Omicron sub-lineage exhibited more severe symptoms at the onset of symptomatic disease but had a shorter viable virus shedding period compared to individuals with BA.1 or BA.2. However, the study did not elucidate whether these differences reflected any variability in severe outcomes as the disease progressed. Additionally, data on BA.4 severity compared to previous sub-lineages are limited. Studies have shown that both BA.4 and BA.5 have a spike protein mutation with the potential for immune evasion (2), which may result in increased severity for BA.4 and BA.5 compared to previous sub-lineages. Herein, we used a case-control study to assess relative severity of BA.4 and BA.5 compared to BA.2 by estimating the differences in risk of severe outcomes following presentation to emergency care. While this has been undertaken in other countries with similar demographics, these studies have been conducted in settings with low vaccine coverage.

Background The emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated. Aim Our aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type. Methods Laboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death. Results Of 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality. Conclusion We found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.