Wednesday, March 10, 2021

BMJ: Risk of Mortality in Patients Infected with SARS-CoV-2 VOC 202012/1 (B.1.1.7)

#15,857

Although there are other variants of concern - like the P.1 variant first reported in Brazil, and the B.1.351 variant in South Africa - the B1.1.7 variant from the UK is the fastest spreading, most widely dispersed (reported in 94 countries), and most studied COVID variant at this time. 

Currently, 97% of the COVID Variants of Concern (VOC) being tracked in the United States by the CDC are B.1.1.7, and the MMWR has forecast this variant to become the dominant COVID virus in the United States this spring (see MMWR: Emergence Of SARS-CoV-2 B.1.1.7 Lineage — United States, Dec 29, 2020–Jan 12, 2021).

While reports of its increased transmissibility began to emerge in December, on the 21st of January, in UK: NERVTAG paper on COVID-19 variant of concern B.1.1.7, we saw the first analyses (from LSHTM, The University of Exeter, Imperial College London and the PHE) suggesting the UK variant B.1.1.7 might be more severe than the the previously dominant `wild type' variants.

Since then we've seen additional studies come out of the UK (see Updated NERVTAG Report On Increased Severity With COVID Variant B.1.1.7) and Denmark (see SSI: COVID Variant B.1.1.7 Now Dominant In Denmark - Increases Risk of Hospitalization 64%) supporting the notion that this variant produces more severe illness, and death than the older `wild type' COVID.

Although the overall fatality rate from COVID B.1.1.7 remains relatively low, today we have additional data - published in the British Medical Journal - suggesting the risk of death from this variant is increased between 32% and 102% with the most probable hazard ratio estimate of 1.64, or 64%.

First a link to the open access BMJ study, then a look at some expert reaction from the Science Media Centre.  

Research
Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study
(Published 10 March 2021) Cite this as: BMJ 2021;372:n579
Robert Challen, postdoctoral research associate123, Ellen Brooks-Pollock, senior lecturer in veterinary public health345,  Jonathan M Read, senior lecturer in epidemiology and biostatistics36, Louise Dyson, associate professor in epidemiology37,  Krasimira Tsaneva-Atanasova, professor of mathematics for healthcare18, Leon Danon, associate professor in infectious disease epidemiology and data analytics3589 

Correspondence to: R Challen rc538@exeter.ac.uk (or @rjchallen on Twitter)
Accepted 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.

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While this study's results are in line with others we've seen, not everyone views their significance in the same way. The two opposing views (below) appear on the Science Media Centre website.  Follow the link to read all of the expert reactions.

MARCH 10, 2021
expert reaction to paper looking at mortality in patients infected with the SARS-CoV-2 variant of concern B.1.1.7

A paper published in the BMJ compares mortality of patients infected with the SARS-CoV-2 variant B.1.1.7, with those infected with previously circulating SARS-CoV-2 variants.

Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:

“This new, peer reviewed study has studied the lethality of the coronavirus that causes Covid-19 by directly comparing the outcomes of individuals infected in the community, either with the B.1.1.7 ‘Kent’ variant or other, pre-existing variants. Other factors such as age, sex, ethnicity and socioeconomic status, could be eliminated by matching results to someone with a similar profile.

“Patients infected with the Kent variant were 64% more likely to die than those infected with other versions of the virus circulating in the UK. While it is important to note that absolute risk remained low, increasing from 2.5 to 4.1 deaths per 1000 cases, this is substantially higher than the 30-40% possible increase reported by Sir Patrick Vallance on 22nd January, which was dismissed as unlikely in some quarters. Unsurprisingly, the increase in lethality is largest in men and increases with age. Further data is needed to make any meaningful conclusions on ethnicity or socioeconomic status.

“It is now well established that the Kent variant is more transmissible; it has come to dominate in the UK and it is increasing in prevalence in other parts of the developed world. This increased lethality, in addition to the increased transmissibility, means that this version of the virus presents a substantial challenge to healthcare systems and policy makers. It also makes it even more important people get vaccinated when called.”


Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:

“Again, I’m still not yet very convinced by these results.

“Clinical teams know that the coldest winter temperatures occurring in Jan/Feb can exacerbate all the comorbidities that predispose to more severe outcomes of COVID-19 – like chronic heart, lung, renal, neurological diseases – including diabetes, hypertension (stressing the heart).

“So without the careful matching of comorbidities in the VOC and non-VOC arms, these differential clinical severity model outcomes are still questionable.

“We really need to revisit this in Spring to account for the cold weather factor – and there are also other seasonal variables related to shorter daylight hours, such as melatonin levels that may impact differentially on VOC vs. non-VOC clinical outcomes – related to host immune responses.

“Also, there is another possible confounder within the last few months which may impact on the VOC/non-VOC unequally, I.e. the winter timing of this 3rd lockdown – which adds to various stress factors due to lack of exercise, increased consumption of junk food, stresses related to home schooling, increased and prolonged economic stress, ongoing lack of attendance for other healthcare problems, etc. which may impact on various host immune responses to these viruses.

“But at the end of the day, we just deal with all such cases as and when they present to the NHS – so this type of analysis does not really impact on that.”
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