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

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.

Interferon Resistance of Emerging SARS-CoV-2 Variants

“…As IFNs are critical in controlling early virus infection levels, IFN-resistant SARS-CoV-2 variants may produce higher viral loads that could in turn promote transmission and/or exacerbate pathogenesis. Consistent with this hypothesis, alarming preliminary reports linked B.1.1.7 with increased viral loads 34 and risk of death [35][36][37] . In addition to Spike, emerging variants exhibited mutations in nucleocapsid, membrane and nonstructural proteins NSP3, NSP6 and NSP12 (Supplementary Table 1).…”

Altered Subgenomic RNA Expression in SARS-CoV-2 B.1.1.7 Infections

“…These findings suggest a potential reason for enhanced transmissibility, though they did not account for potential confounders such as days since symptom onset at sampling. Many of these studies also use S gene target failure (SGTF) as a surrogate for the presence of B.1.1.7 ( 6 ) , which might misclassify samples, depending on the prevalence of B.1.1.7 ( 8 ) . Several analyses from community tested cases also suggest increased mortality associated with B.1.1.7 ( 8 ) .…”

“…Many of these studies also use S gene target failure (SGTF) as a surrogate for the presence of B.1.1.7 ( 6 ) , which might misclassify samples, depending on the prevalence of B.1.1.7 ( 8 ) . Several analyses from community tested cases also suggest increased mortality associated with B.1.1.7 ( 8 ) . Reasons for the potential viral load increase and enhanced mortality are currently unclear ( 9 ) .…”

Increased transmission of SARS-CoV-2 lineage B.1.1.7 (VOC 2020212/01) is not accounted for by a replicative advantage in primary airway cells or antibody escape

“…infection results in an approximately 70% higher hazard of death compared to other strains (Challen et al, 2021;Davies et al, 2021). To effectively control SARS-CoV-2 and to assess the risk of future variants, it is vital to understand the phenotypic characteristics and the underpinning mutations which have resulted in the higher transmissibility and pathogenicity of the B.1.1.7 lineage.…”