Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7

Cell Reports · 2021 · 448 citations

• Biology
• Virology
• Chemistry

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

The Lancet Public Health · 2021 · 343 citations

• Medicine
• Demography
• Internal medicine

BACKGROUND: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. METHODS: , for the two incidence estimates. FINDINGS: fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. INTERPRETATION: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. FUNDING: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

The Lancet Infectious Diseases · 2021 · 547 citations

• Medicine
• Emergency medicine
• Internal medicine

Background: The SARS-CoV-2 Delta (B.1.617.2) variant was first detected in England in March 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the Delta variant is associated with more severe disease than the previously dominant Alpha (B.1.1.7) variant. Methods: Individual-level data on 43,338 COVID-19-positive cases (median age 31 years, inter-quartile range 17-43) in England between 29 March and 23 May 2021 and whose positive specimen had undergone whole genome sequencing were linked to routine healthcare datasets on vaccination, emergency care attendance, hospital admission and mortality. Hospital attendance and admission outcomes were compared between cases with sequencing-confirmed Delta and Alpha variants. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar period and vaccination status. Findings: There were 960 hospital admissions (2.5%) and 1,946 hospital admissions or emergency care attendances (4.5%) within 14 days. The adjusted hazard ratio (HR) for Delta vs Alpha cases was 2.26 (95% CI 1.32-3.89) of hospital admission within 14 days, and 1.45 (95% CI 1.08-1.95) of emergency care attendance or hospital admission within 14 days. Most cases were unvaccinated (32,078/43,338, 74%). The HRs for vaccinated Delta vs Alpha cases were similar to the HRs for unvaccinated Delta vs Alpha cases, but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher emergency care attendance or hospital admission risk for COVID-19 cases infected with the Delta compared with the Alpha variant. While rates of hospital care among vaccinated individuals were low overall, results suggest that outbreaks of the Delta variant in unvaccinated populations may lead to a greater burden on healthcare services than the Alpha variant. Funding: Medical Research Council and MRC UKRI/DHSC NIHR.

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells

iScience · 2021 · 91 citations

• Virology
• Biology
• Computational biology

. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.