Mechanical ventilation

2019-20 coronavirus outbreak

Jury

Sars virus

Betacoronavirus

Cohort

Virology

Mann–Whitney U test

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Outbreak

Tocilizumab

Coronavirus disease 2019 (COVID-19)

Pediatrics

Political science

Infectious disease (medical specialty)

Internal medicine

Wilcoxon signed-rank test

Medicine

Disease

Severity of illness

Mortality rate

The Lancet Infectious Diseases

Dan Frampton and colleagues1Frampton D Rampling T Cross A et al.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.Lancet Infect Dis. 2021; (published online April 12.)https://doi.org/10.1016/S1473-3099(21)00170-5Summary Full Text Full Text PDF PubMed Scopus (272) Google Scholar 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 χ2 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, dexamethasone, 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,2Challen R Brooks-Pollock E Read JM Dyson L Tsaneva-Atanasova K Danon L Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study.BMJ. 2021; 372: n579Crossref PubMed Scopus (508) Google Scholar 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 colleagues3Davies NG Jarvis CI Edmunds WJ Jewell NP Diaz-Ordaz K Keogh RH Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7.Nature. 2021; 593: 270-274Crossref PubMed Scopus (620) Google Scholar 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.TableDemographics and outcomes of cases of SARS-CoV-2 infection with B.1.1.7 variant compared with non-B.1.1.7 variantsnInfection with B.1.1.7 variantnInfection with a non-B.1.1.7 variantp valueDate of first positive PCR swab30Dec 3–20, 202030Oct 10–Dec 20, 2020..Age (years)3077 (59–88)3079 (59–87)0·976Sex30..30..0·436Male..15 (50%)..18 (60%)..Female..15 (50%)..12 (40%)..Number of comorbidities302 (1–3)302 (1–3)0·845White ethnicity (%)3026 (87%)3030 (100%)0·112NEWS2*NEWS=National Early Warning Score. *The NEWS2 score was not calculated at maximum FiO2.30..30....At presentation..4 (2–7)..2·5 (1–6)0·135Maximum value..6 (4–8)..5 (3–9)0·345Respiratory rate oxygenation index..........At presentation3020 (15–26)3024 (15–27)0·371At maximum FiO22515 (11–21)2618 (13–26)0.341Sequential Organ Failure Assessment score30..30....At presentation..3·0 (2–7)..3·5 (2–6)0·858At maximum FiO2..5·5 (2–7)..5·0 (2–7)0·5664C Mortality Score30..30....At presentation..12·0 (9·0–14·8)..10·5 (9·0–14·0)0·568At maximum FiO2..12·5 (8·3–14·0)..11·5 (9·0–13·0)0·463Maximum ventilatory support received30..30..0·265Mechanical ventilation..3 (10%)..1 (3%)..Non-invasive ventilation..0 (0%)..1 (3%)..Standard oxygen therapy..18 (60%)..14 (47%)..No supplemental oxygen required..9 (30%)..14 (47%)..Treatment..........Dexamethasone1813 (72%)2410 (42%)0·049Remdesivir142 (14%)221 (5%)0·547Anticoagulation244 (17%)308 (27%)0·380Tocilizumab281 (4%)280 (0%)1·00028-day mortality (%, 95% CI)289 (32·1%, 17·9–50·7)296 (20·7%, 9·8–38·4)0·326Patients with a severe clinical outcome†A severe clinical outcome was defined as a WHO scale score by day 14 after symptom onset or the first positive SARS-CoV-2 PCR of at least 6 or death within 28 days.3011 (37%)308 (27%)0·405Data are n (%) or median (IQR), unless otherwise stated. FiO2=fraction of inspired oxygen.* NEWS=National Early Warning Score. *The NEWS2 score was not calculated at maximum FiO2.† A severe clinical outcome was defined as a WHO scale score by day 14 after symptom onset or the first positive SARS-CoV-2 PCR of at least 6 or death within 28 days. Open table in a new tab Data are n (%) or median (IQR), unless otherwise stated. FiO2=fraction of inspired oxygen. 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 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. AC reports grants from NIHR, Asthma UK, Boehringer-Ingelheim Charity; consulting fees and honoraria from Sanofi; and support for meeting attendance from GSK. All other authors declare no competing interests. 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 studyEmerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. Full-Text PDF Open Access

The SARS-CoV-2 B.1.1.7 variant and increased clinical severity—the jury is out