The SARS-CoV-2 Alpha variant is associated with increased clinical severity of COVID-19 in Scotland: a genomics-based retrospective cohort analysis

Abstract

Background The Alpha (B.1.1.7) SARS-CoV-2 variant of concern has been associated with increased transmission and increased 28-day mortality. We aimed to investigate the impact of infection on clinical severity of illness, including the need for oxygen or ventilation in a national cohort study. Methods In this prospective clinical cohort study, 1475 SARS-CoV-2 sequences were obtained from patients infected in Scotland, UK between the 1st November 2020 and 30th January 2021 and matched to clinical outcomes as the lineage became dominant in Scotland. We modelled the association between B.1.1.7 infection and severe disease using a cumulative generalised linear mixed model employing a 4-point scale of maximum severity based on requirement of respiratory support at 28 days. We also estimated the growth rate of B.1.1.7-associated infections as it emerged in Scotland using a phylogenetic exponential growth rate population model. Results The B.1.1.7 lineage was responsible for a third wave of SARS-CoV-2 infection in Scotland in association with a transmission rate 5-fold higher than the preceding second wave B.1.177 lineage. Of 1475 patients, 364 were infected with B.1.1.7, 1030 with B.1.177 and 81 with other lineages. Our analysis found a positive association between increased clinical severity and lineage (B.1.1.7 versus non-B.1.1.7; cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93). Viral load was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold (Ct) value (mean Ct change: -2.46, 95% CI: -4.22, -0.70). Conclusions The B.1.1.7 lineage was associated with more severe clinical disease in Scottish patients than co-circulating lineages.

Inconsistent directions of change in case severity across successive SARS-CoV-2 variant waves suggests an unpredictable future

“…For Alpha versus previous variants, most previous studies have also estimated an increase in severity over extant diversity. A wide variety of end points have been used, 28-day mortality, hospitalisation, and an ordinal scale based around supplemental oxygen[17-27]. Our estimates are consistent with the majority of these studies.…”

A Case Report: Genetically Distinct Severe Acute Respiratory Syndrome Coronavirus-2 Variant Causing Reinfection

“…Of particular interest seems to be Q27 * and K68 * stop codons in open reading frame 8 (ORF8), which might play a role in immune evasion (Zhang et al, 2020;Zinzula, 2021). The lineage B.1.1.7 (Alpha) has been associated with evidence of increased hospitalization, mortality, transmissibility, severity, and possible immune evasion with potential implications for reinfection and vaccine effectiveness in patients (Pascall et al, 2021). These findings concern whether the immunity acquired by natural infection or mass vaccination could confer adequate protection against the constantly evolving SARS-CoV-2.…”

Severity of Covid-19 Cases in the Months of Predominance of the Alpha Variant and the Role of Vaccination

“…Their results suggested some controversial differences. Some studies demonstrated that the Alpha variant may increase the risk of ICU admission and the mortality (3,4). Other studies concluded that there were no signi cant differences (5).…”

“…Mortality was 2.7 times higher with the Alpha variant than with the presence of the Delta variant. This risk may be related to the fact that the Alpha may be more aggressive (3,4).…”

“…A previous study analysed the main symptoms of the Alpha variant by patient characteristics and the role of vaccination. Some studies (3,4) found an association between the Alpha variant and an increase in hospitalization, ICU admission and mortality. However, Veneti and et al (5) found no differences in the risk of hospitalisation between reported cases of the SARS-CoV-2 Delta and Alpha variants in Norway.…”