Increased hazard of mortality in cases compatible with SARS-CoV-2 variant of concern 202012/1 - a matched cohort study

Abstract

Objectives - To establish whether there is any change in mortality associated with infection of a new variant of SARS-CoV-2 (VOC-202012/1), first detected in UK in December 2020, compared to that associated with infection with circulating SARS-CoV-2 variants. Design - Matched cohort study. Cases are matched by age, gender, ethnicity, index of multiple deprivation, lower tier local authority region, and sample date of positive specimen, and differing only by detectability of the spike protein gene using the TaqPath assay - a proxy measure of VOC-202012/1 infection. Setting - United Kingdom, Pillar 2 COVID-19 testing centres using the taqPath assay. Participants - 54,773 pairs of participants testing positive for SARS-CoV-2 in Pillar 2 between 1st October 2020 and 29th January 2021. Main outcome measures - Death within 28 days of first positive SARS-CoV-2 test. Results - There is a high probability that the risk of mortality is increased by infection with VOC-202012/01 (p <0.001). The mortality hazard ratio associated with infection with VOC-202012/1 compared to infection with previous strains is 1.7 (95% CI 1.3 - 2.2) in patients who have tested positive for COVID-19 in the community. In this comparatively low risk group, this represents an increase of deaths from 1.8 in 1000 to 3.1 in 1000 detected cases. Conclusions - If this finding is generalisable to other populations, VOC-202012/1 infections have the potential to cause substantial additional mortality over and previously circulating variants. Healthcare capacity planning, 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.

SARS-CoV-2 one year on: evidence for ongoing viral adaptation

“…Interestingly, the aforementioned UK B.1.1.7 lineage, assumed to have arisen from an immunocompromised individual, contains a premature stop codon at position 27 of ORF8 – it is highly likely this results in loss of function of the accessory protein, similar to the Singapore cluster [87, 145, 146]. However, unlike the Singapore cluster, B.1.1.7 has been found to have a higher case fatality rate than other circulating lineages [89, 90], potentially due to the complex set of mutations in this variant of concern. Additionally, a single case report from an immunocompromised patient also included a premature stop codon in ORF8, similar to the B.1.1.7 lineage [71].…”

“…In December 2020, a cluster of COVID-19 cases (known variously as B.1.1.7, 20B/501Y.V1, or VOC/202012/01) was detected in South East England [87]. This cluster showed evidence of higher transmissibility in the community compared to contemporary strains [88], significantly higher case-fatality rates [89, 90], and, depending on the study, lower Ct values from diagnostic PCR tests on clinical swabs [91–94]. In the UK, B.1.1.7 is now the predominant lineage, accounting for >90 % of infections [95].…”

Bayesian inference across multiple models suggests a strong increase in lethality of COVID-19 in late 2020 in the UK

“…It is natural to speculate that the increase is related to the emergence of one or more new virus strains, whose potentially increased lethality has been the subject of several cohort-based studies summarised previously in a UK Government publication [5]. Those works estimate a lethality increase for B.1.1.7 by factors ranging up to 1.7 [23]. In contrast, a study by Davies et al using a compartmented model including two virus strains [24] did not produce clear evidence for any change in severity (only a large increase transmissibility).…”

Spatio-temporal estimation of basic and effective reproduction number of COVID-19 and post-lockdown transmissibility in Bangladesh

“…The new variant is estimated to be 70% more transmissible than previous circulating variants [ 41 ]. Moreover, variant B.1.1.7 is 64% more lethal than the previously circulating variants [ 43 ]. People who catch the new variant are infected for a relatively long time [ 44 ]; thus, a more extended quarantine period might be warranted for passengers coming from UK in Bangladesh.…”