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

Abstract

Objective: To establish whether there is any change in mortality from infection with a new variant of SARS-CoV-2, designated a variant of concern (VOC-202012/1) in December 2020, compared with circulating SARS-CoV-2 variants.

Design: Matched cohort study.

Setting: Community based (pillar 2) covid-19 testing centres in the UK using the TaqPath assay (a proxy measure of VOC-202012/1 infection).

Participants: 54 906 matched pairs of participants who tested positive for SARS-CoV-2 in pillar 2 between 1 October 2020 and 29 January 2021, followed-up until 12 February 2021. Participants were matched on age, sex, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimens, and differed only by detectability of the spike protein gene using the TaqPath assay.

Main outcome measure: Death within 28 days of the first positive SARS-CoV-2 test result.

Results: The mortality hazard ratio associated with infection with VOC-202012/1 compared with infection with previously circulating variants was 1.64 (95% confidence interval 1.32 to 2.04) in patients who tested positive for covid-19 in the community. In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases.

Conclusions: The probability that the risk of mortality is increased by infection with VOC-202012/01 is high. If this finding is generalisable to other populations, infection with VOC-202012/1 has the potential to cause substantial additional mortality compared with previously circulating variants. Healthcare capacity planning and national and international control policies are all impacted by this finding, with increased mortality lending weight to the argument that further coordinated and stringent measures are justified to reduce deaths from SARS-CoV-2.

Fig 1

Sample selection algorithm showing average figures for numbers of participants in each study arm. Matching involved random sampling to create 50 replicates. Some cases were excluded for more than one reason

Fig 2

Kaplan-Meier survival curve for S gene positive (previously circulating variants) and S gene negative (new variant VOC-202012/1) participants in the UK. The y axis has been truncated as mortality was low in both groups

Fig 3

Investigation of biases in S gene positive and S gene negative study arms

Fig 4

Sensitivity analyses. Red bar indicates default assumptions (cycle threshold <30; age tolerance ±5 years; sample date tolerance ±1 day) from rest of study