New cohort analyses show the popular UK variant is linked to a higher viral load, though patients have not experienced worse likelihood of outcomes.
SARS-CoV-2 variant B.1.1.7. is associated with increased transmissibility of the pandemic virus, but not linked to increased likelihood of hospitalization, according to new data.
In research presented by a team of London investigators and published to The Lancet Monday evening, the prominent strain of the COVID-19 variant—which was initially reported in outbreaks in southeast England in late 2020—was indeed sequenced more frequently than the common SARS-CoV-2 virus among hundreds of real-world patients who tested positive.
The cohort assessment also reported an increased virus load by proxy associated with B.1.1.7, despite there being no link to more severe disease likelihood—a buck against research trends suggesting an association between SARS-CoV-2 viral load and mortality.
To the knowledge of the investigators, there has been no peer-reviewed assessment of combined virus genomic data and clinical outcomes of patients with B.1.1.7 infection versus other SARS-Cov-2 variants.
“Our report gives an early assessment of the B.1.1.7 variant’s genomic characteristics and associated clinical outcomes, bridging the period over which B.1.1.7 became the predominant strain in two north-central London hospitals,” investigators wrote.
The investigators conducted a sequencing and assessment of PCR-positive samples of SARS-CoV-2 that were collected from 2 London hospitals from November 9 to December 20, 2020. They sought B.1.1.7 variant of concern (VOC)-defining mutations in each confirmed infection.
The association between B.1.1.7 infection and severe COVID-19, as well as that of the mutation and death, was assessed with Poisson regression models within 28 days of a positive test.
Supplementary genomic analyses were conducted in a cohort of patients chronically shedding virus, as well as a cohort of patients being treated for COVID-19 with remdesivir. Among these patients, viral load was compared by proxy, via PCR cycle threshold metrics and sequencing read depths.
Investigators’ inclusion criteria featured 496 patients with PCR-positive SARS-CoV-2. Among them, 341 had samples that could be sequenced. Of those, 198 (58%) were observed to be B.1.1.7 infections; the remaining 143 (42%) were another virus strain.
The prevalence ratio (PR) of severe COVID-19—as per point ≥6 on the WHO ordinal scale for COVID-19 severity—or death associated with B.1.1.7 lineage was just 0.97 (95% CI, 0.72 – 1.31), indicating an insignificant likelihood. When adjusted for hospital of care, patient sex, age, comorbidities, and ethnicity, the variant lineage was associated with a slightly higher PR of 1.02 (95% CI, 0.76 – 1.38).
The team reported no VOC-defining mutations among 123 immunocompromised patients chronically shedding virus, or in 32 patients treated with remdesivir. Viral load by proxy was greater in B.1.1.7 samples versus other SARS-CoV-2 samples by both cycle threshold value (mean 28.8 vs 32.0; P = .0085) and genomic read depth (1280 vs 831; P = .0011).
In discussing the viral load findings, the investigators noted their outcomes were consistent with independent analyses which have shown greater counts among B.1.1.7 samples.
“Although our data show that B.1.1.7 was associated with an increased viral load by proxy of PCR Ct values and NGS read depth in the nasopharynx, we saw no association between B.1.1.7 and severity,” they wrote. “Previous studies have suggested an association between viral load and mortality.”
They concluded that the data, combined with in-vitro assessment of neutralization capacity of vaccinated persons and those who have recovered from natural infection, are vital comprehensive measures of COVID-19 understanding.
“Large readily available datasets will be key in enabling rapid clinical assessment of variants,” they wrote. “Our data, within the context and limitations of a real-world study, provide initial reassurance that severity in hospitalized patients with B.1.1.7 is not markedly different from severity in those without, and this study provides a model to answer the same question again as we move into an era of emerging variants.”