UK variant associated with a significantly higher mortality — Two studies

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The highly infectious variant of COVID-19 discovered in Kent, which swept across the UK last year before spreading worldwide, is between 30% and 100% more deadly than previous strains, analysis has shown.

A study, by epidemiologists from the Universities of Exeter and Bristol, has shown that the SARS-CoV-2 variant, B.1.1.7, is associated with a significantly higher mortality rate amongst adults diagnosed in the community compared to previously circulating strains. A second study, published in Nature, estimate a 61% higher hazard of death.

The first study compared death rates among people infected with the new variant and those infected with other strains.

It showed that the new variant led to 227 deaths in a sample of 54,906 patients – compared to 141 amongst the same number of closely matched patients who had the previous strains.

With the new variant already detected in more than 50 countries worldwide, the analysis provides crucial information to governments and health officials to help prevent its spread.

Robert Challen, lead author of the study from the University of Exeter said: "In the community, death from COVID-19 is still a rare event, but the B.1.1.7 variant raises the risk. Coupled with its ability to spread rapidly this makes B.1.1.7 a threat that should be taken seriously."

The Kent variant, first detected in the UK in September 2020, has been identified as being significantly quicker and easier to spread, and was behind the introduction of new lockdown rules across the UK from January.

The study shows that the higher transmissibility of the Kent strain meant that more people who would have previously been considered low risk were hospitalised with the newer variant.

Having analysed data from 54,609 matched pairs of patients of all age-groups and demographics, and differing only in strain detected, the team found that there were 227 deaths attributed to the new strain, compared to 141 attributable to earlier strains.

Leon Danon, senior author of the study from the University of Bristol said: "We focussed our analysis on cases that occurred between November 2020 and January 2021, when both the old variants and the new variant were present in the UK. This meant we were able to maximise the number of "matches" and reduce the impact of other biases. Subsequent analyses have confirmed our results.

"SARS-CoV-2 appears able to mutate quickly, and there is a real concern that other variants will arise with resistance to rapidly rolled out vaccines. Monitoring for new variants as they arise, measuring their characteristics and acting appropriately needs to be a key part of the public health response in the future."

Ellen Brooks-Pollock from the University of Bristol expanded: "It was fortunate the mutation happened in a part of the genome covered by routine testing. Future mutations could arise and spread unchecked."

 

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

Robert Challen, Ellen Brooks-Pollock, Jonathan M Read, Louise Dyson, Krasimira Tsaneva-Atanasova, Leon Danon

Published in BMJ on 25 February 2021

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.

The B.1.1.7 variant of SARS-CoV-2, which was first identified in the UK, may be associated with an increased risk of death, a study suggests. The findings, based on an analysis of more than 2m community test results and over 17,000 COVID-19 deaths in England from September 2020 to February 2021, may have implications for the future of the SARS-CoV-2 pandemic and efforts to curtail it.

The B.1.1.7 variant, which was first detected in the UK in September 2020, has now spread to many countries around the world. Studies have established that it is more transmissible than pre-existing variants, but its effect on the mortality of disease has been uncertain.

Nicholas Davies and colleagues at the London School of Hygiene and Tropical Medicine, analysed a database of 2,245,263 positive SARS-CoV-2 community test results and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 of the community tests (51%), the presence or absence of the B.1.1.7 variant can be identified owing to mutations in the spike gene of this variant, which produce a negative result for this gene in certain diagnostic tests for SARS-CoV-2 (known as a spike gene target failure).

Using data from 4,945 deaths, the authors estimate that in tests that resulted in a spike gene target failure, the risk of death was 55% higher than that for people infected with other pre-existing variants when adjusted for several factors including age, sex and ethnicity.

This corresponds to an absolute risk of death for a male aged 55 to 69 increasing from 0.6% to 0.9% over the 28 days after a positive test. The authors note that some other circulating SARS-CoV-2 lineages could also cause a spike gene target failure in tests. Thus, they used a modelling approach to correct for misclassification of the potential variants and estimate that there was a 61% higher risk of death associated with the B.1.1.7 variant.

 

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

Nicholas G Davies, Christopher I Jarvis, CMMID COVID-19 Working Group, W John Edmunds, Nicholas P Jewell, Karla Diaz-Ordaz Ruth H Keogh

Published in Nature on 15 March 2021

Abstract
SARS-CoV-2 lineage B.1.1.7, a variant first detected in the UK in September 20201, has spread to multiple countries worldwide. Several studies have established that B.1.1.7 is more transmissible than pre-existing variants, but have not identified whether it leads to any change in disease severity2. Here we analyse a dataset linking 2,245,263 positive SARS-CoV-2 community tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021. For 1,146,534 (51%) of these tests, the presence or absence of B.1.1.7 can be identified because of mutations in this lineage preventing PCR amplification of the spike gene target (S gene target failure, SGTF1). Based on 4,945 deaths with known SGTF status, we estimate that the hazard of death associated with SGTF is 55% (95% CI 39–72%) higher after adjustment for age, sex, ethnicity, deprivation, care home residence, local authority of residence and test date. This corresponds to the absolute risk of death for a 55–69-year-old male increasing from 0.6% to 0.9% (95% CI 0.8–1.0%) within 28 days after a positive test in the community. Correcting for misclassification of SGTF and missingness in SGTF status, we estimate a 61% (42–82%) higher hazard of death associated with B.1.1.7. Our analysis suggests that B.1.1.7 is not only more transmissible than pre-existing SARS-CoV-2 variants, but may also cause more severe illness.

 

Nature study (Restricted access)

 

University of Exeter material

 

BMJ study (Open access)

 

Nature study (Restricted access)

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