Mortality and critical care unit admission associated with the SARS-CoV-2 lineage B.1.1.7 in England: an observational cohort study

Abstract

Background: A more transmissible variant of SARS-CoV-2, the variant of concern 202012/01 or lineage B.1.1.7, has emerged in the UK. We aimed to estimate the risk of critical care admission, mortality in patients who are critically ill, and overall mortality associated with lineage B.1.1.7 compared with non-B.1.1.7. We also compared clinical outcomes between these two groups.

Methods: For this observational cohort study, we linked large primary care (QResearch), national critical care (Intensive Care National Audit & Research Centre Case Mix Programme), and national COVID-19 testing (Public Health England) databases. We used SARS-CoV-2 positive samples with S-gene molecular diagnostic assay failure (SGTF) as a proxy for the presence of lineage B.1.1.7. We extracted two cohorts from the data: the primary care cohort, comprising patients in primary care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 26, 2021, and known SGTF status; and the critical care cohort, comprising patients admitted for critical care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 27, 2021, and known SGTF status. We explored the associations between SARS-CoV-2 infection with and without lineage B.1.1.7 and admission to a critical care unit (CCU), 28-day mortality, and 28-day mortality following CCU admission. We used Royston-Parmar models adjusted for age, sex, geographical region, other sociodemographic factors (deprivation index, ethnicity, household housing category, and smoking status for the primary care cohort; and ethnicity, body-mass index, deprivation index, and dependency before admission to acute hospital for the CCU cohort), and comorbidities (asthma, chronic obstructive pulmonary disease, type 1 and 2 diabetes, and hypertension for the primary care cohort; and cardiovascular disease, respiratory disease, metastatic disease, and immunocompromised conditions for the CCU cohort). We reported information on types and duration of organ support for the B.1.1.7 and non-B.1.1.7 groups.

Findings: The primary care cohort included 198 420 patients with SARS-CoV-2 infection. Of these, 117 926 (59·4%) had lineage B.1.1.7, 836 (0·4%) were admitted to CCU, and 899 (0·4%) died within 28 days. The critical care cohort included 4272 patients admitted to CCU. Of these, 2685 (62·8%) had lineage B.1.1.7 and 662 (15·5%) died at the end of critical care. In the primary care cohort, we estimated adjusted hazard ratios (HRs) of 2·15 (95% CI 1·75-2·65) for CCU admission and 1·65 (1·36-2·01) for 28-day mortality for patients with lineage B.1.1.7 compared with the non-B.1.1.7 group. The adjusted HR for mortality in critical care, estimated with the critical care cohort, was 0·91 (0·76-1·09) for patients with lineage B.1.1.7 compared with those with non-B.1.1.7 infection.

Interpretation: Patients with lineage B.1.1.7 were at increased risk of CCU admission and 28-day mortality compared with patients with non-B.1.1.7 SARS-CoV-2. For patients receiving critical care, mortality appeared to be independent of virus strain. Our findings emphasise the importance of measures to control exposure to and infection with COVID-19.

Funding: Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, and the Medical Sciences Division of the University of Oxford.

Figure 1

Flowchart of the primary care cohort and the critical care cohort ICNARC=Intensive Care National Audit & Research Centre. PHE=Public Health England. SGTF=S-gene molecular diagnostic assay failure. *SGTF is used as a proxy for lineage B.1.1.7.

Figure 2

Risk of 28-days mortality and critical care admission in the primary care cohort, and mortality in the critical care cohort SGTF was used as a proxy for lineage B.1.1.7. INARC=Intensive Care National Audit & Research. HR=hazard ratio. PHE=Public Health England. SGTF=S-gene molecular diagnostic assay failure. *Unadjusted, complete case analysis for the period between Nov 1, 2020, and Feb 23, 2021; data sources: QReserach, INARC COVID−19 study, and PHE. †Unadjusted, complete case analysis for the period between Nov 1, 2020, and Jan 7, 2021; data sources: QReserach, INARC COVID−19 study, and PHE. ‡Analysis for the period between Nov 1, 2020, and Jan 27, 2021; data sources: ICNARC and PHE.

Figure 3

Estimated adjusted HR for critical care admission in the primary care cohort Adjusted, complete case analysis for the period between Nov 1, 2020, and Jan 26, 2021. Data sources used were QReserach, Intensive Care National Audit & Research COVID−19 study, and Public Health England. S-gene molecular diagnostic assay failure was used as a proxy for lineage B.1.1.7. HR=hazard ratio.