key: cord-0896643-bf5c8q2m
authors: Giles, Benjamin; Meredith, Paul; Robson, Samuel; Smith, Gary; Chauhan, Anoop
title: The SARS-CoV-2 B.1.1.7 variant and increased clinical severity—the jury is out
date: 2021-06-28
journal: Lancet Infect Dis
DOI: 10.1016/s1473-3099(21)00356-x
sha: 332f58121bd15ee392aa56be17cdf69847265503
doc_id: 896643
cord_uid: bf5c8q2m

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the WHO clinical progression ordinal scale used by Frampton and colleagues) with physiological measures, and assess the impact of viral load, novel treatments, and vaccinations. For the purposes of future case-control studies, we estimate post-hoc that a sample size of 234 patients in each group is required to detect an effect size of 11·4% in 28-day mortality for a baseline mortality in the control group of 20·7% at 80% power with 5% significance. We believe the jury is still out on whether B.1.1.7 infections are associated with increased mortality, with more time and data required.

The SARS-CoV-2 B.1.1.7 variant and increased clinical severity-the jury is out Dan Frampton and colleagues 1 demonstrated increased viral load but not severity of disease or 28-day mortality in hospitalised patients infected by the B.1.1.7 variant of SARS-CoV-2. By contrast, we found slightly different results when assessing the risk of morbidity and mortality in a matched case-control study in 60 hospitalised patients-30 with the B.1.1.7 variant and 30 with non-B.1.1.7 variants. Cases were matched for admission period and age band. Clinical severity scores, requirement for ventilation, treatments received, and 28-day mortality were compared between groups using anonymised, retrospectively collected data and Wilcoxon rank-sum and χ 2 or Fisher's exact tests.

Our findings (table) show consistent and rational evidence that patients infected with the B.1.1.7 variant developed more serious disease: they had greater clinical severity (eg, higher National Early Warning Score value, lower respiratory rate oxygenation index) and greater requirement for supplemental oxygen and mechanical ventilation, they more often received approved treatments for SARS-CoV-2 infection (eg, dexa methasone, remdesivir, and tocilizumab), and they had more serious clinical outcomes (ie, higher 28-day mortality, WHO clinical progression scale score). Although our results show a tendency towards severe disease with B.1.1.7 infection, it is likely that our study was underpowered as statistical significance was seen only for patients requiring dexamethasone. Nevertheless, our data echo the findings of other, larger studies. For example, Challen and colleagues, 2 who studied a younger population than described here or studied by Frampton and colleagues, with likely less comorbidity, found a 64% increase in 28-day mortality following community infection with the B.1.1.7 variant (control group, 0·26%; B.1.1.7 variant group, 0·41%). Similarly, Davies and colleagues 3 concluded that infections with the B.1.1.7 variant were associated with a hazard of death of 61% (95% CI 42-82) higher than with pre-existing variants.

We believe that the identification of any increased morbidity and mortality risks in patients infected by SARS-CoV-2 variants of concern requires adequately powered studies that use a combination of community and hospital PCR swabs, examine disease severity using more detailed clinical severity scores (such as 

Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study

Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7

Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study