Avian Flu Diary: LSHTM Preprint: Increased Hazard of Death in Community-tested Cases of SARS-CoV-2 Variant of Concern 202012/01

Mutation of SARS-CoV2 - current variants of concern - ECDC

#15,785

Two weeks ago today, in UK: NERVTAG paper on COVID-19 variant of concern B.1.1.7, we saw the first official acknowledgement that the UK COVID B.1.1.7 variant (aka VOC 202012/01) might carry a higher fatality rate than the older, `wild type' COVID.

The NERVTAG report cited several unpublished studies suggesting at least a 35% greater fatality rate:

a. LSHTM: reported that the relative hazard of death within 28 days of test for VOC-infected individuals compared to non-VOC was 1.35 (95%CI 1.08-1.68).
b. Imperial College London: mean ratio of CFR for VOC-infected individuals compared to non-VOC was 1.36 (95%CI 1.18-1.56) by a case-control weighting method, 1.29 (95%CI 1.07-1.54) by a standardised CFR method.
c. University of Exeter: mortality hazard ratio for VOC-infected individuals compared to non-VOC was 1.91 (1.35 - 2.71).

Since then we've seen other sources - including our CDC - acknowledge the possibility that this variant is not only more transmissible, but may cause more severe illness as well. The CDC describes the B.1.1.7 variant as:

The United Kingdom (UK) identified a variant called B.1.1.7 with a large number of mutations in the fall of 2020. This variant spreads more easily and quickly than other variants. In January 2021, experts in the UK reported that this variant may be associated with an increased risk of death compared to other variant viruses, but more studies are needed to confirm this finding. It has since been detected in many countries around the world. This variant was first detected in the US at the end of December 2020.

There are, admittedly, thousands of variants around the world but only a few have been pegged as posing a greater threat to public health. The B.1.1.7 (aka VOC 202012/01) variant is thus far, the most examined of these emerging variants.

Yesterday researchers at the London School of Health & Tropical Medicine published the results of their study as a preprint on MedRxiv server.

Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01
Nicholas G Davies, Christopher I Jarvis, CMMID COVID-19 Working Group, W. John Edmunds, Nicholas P. Jewell, Karla Diaz-Ordaz, Ruth H. Keogh
doi: https://doi.org/10.1101/2021.02.01.21250959
This article is a preprint and has not been certified by peer review [what does this mean?

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Abstract

VOC 202012/01, a SARS-CoV-2 variant first detected in the United Kingdom in September 2020, has spread to multiple countries worldwide. Several studies have established that this novel variant is more transmissible than preexisting variants of SARS-CoV-2, but have not identified whether the new variant leads to any change in disease severity.

We analyse a large database of SARS-CoV-2 community test results and COVID-19 deaths for England, representing approximately 47% of all SARS-CoV-2 community tests and 7% of COVID-19 deaths in England from 1 September 2020 to 22 January 2021. Fortuitously, these SARS-CoV-2 tests can identify VOC 202012/01 because mutations in this lineage prevent PCR amplification of the spike gene target (S gene target failure, SGTF).

We estimate that the hazard of death among SGTF cases is 30% (95% CI 9-56%) higher than among non-SGTF cases after adjustment for age, sex, ethnicity, deprivation level, care home residence, local authority of residence and date of test. In absolute terms, this increased hazard of death corresponds to the risk of death for a male aged 55-69 increasing from 0.56% to 0.73% (95% CI 0.60-0.86%) over the 28 days following a positive SARS-CoV-2 test in the community.

Correcting for misclassification of SGTF, we estimate a 35% (12-64%) higher hazard of death associated with VOC 202012/01. Our analysis suggests that VOC 202012/01 is not only more transmissible than preexisting SARS-CoV-2 variants but may also cause more severe illness.

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While a 35% increase in the risk of death from COVID is not something we want to see, in absolute terms, the risk of dying from the disease - particularly among those under the age of 55 - remains low.

But as the following excerpt illustrates, it becomes far more significant the older the COVID cases are.

Absolute risks

To estimate absolute risks for individuals with VOC 202012/01, we applied the 28- and 60-day hazard ratios obtained for SGTF and pVOC to the baseline (i.e. not variant-specific) risk estimated from all specimens taken between 1 August and 31 October 2020 (Table 5). The absolute risk remains low amongst age groups less than 54, and the absolute risk was higher in males compared to females.

For SGTF, in females aged 70–84 the risk of death within 28 days increased from 2.9% to 3.7% (95% CI 3.1–4.4%) and for females 85 or older increased from 12.8% to 16.4% (13.7–19.0%). For males aged 70–84 the risk of death within 28 days increased from 4.7% to 6.1% (5.0–7.1%) and for males 85 or older increased from 17.1% to 21.7% (18.3– 25.1%).

Estimates of the absolute risk at 60 days were higher than those for 28 days and show similar patterns, with the largest increase of 17.1% to 22.3% (18.6–26.1%) in males 85 years and older. Estimates based on pVOC were marginally higher. These estimates reflect a substantial increase in absolute risk amongst older age groups. Note that these estimates do not reflect the infection fatality ratio, but the fatality ratio among people tested in the community, and are thus likely to be higher than the infection fatality rate as many infected individuals will not have been tested.

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B.1.1.7 (and other) variants are moving targets, with the ability to mutate and adapt over time. Just a few days ago we learned that E484K Mutation had been Detected In A Small Number of B.1.1.7 Variant VIruses in the UK.