Increased infections, but not viral burden, with a new SARS-CoV-2 variant

Abstract

BackgroundA new variant of SARS-CoV-2, B.1.1.7/VOC202012/01, was identified in the UK in December-2020. Direct estimates of its potential to enhance transmission are limited.MethodsNose and throat swabs from 28-September-2020 to 2-January-2021 in the UK’s nationally representative surveillance study were tested by RT-PCR for three genes (N, S and ORF1ab). Those positive only on ORF1ab+N, S-gene target failures (SGTF), are compatible with B.1.1.7/VOC202012/01. We investigated cycle threshold (Ct) values (a proxy for viral load), percentage of positives, population positivity and growth rates in SGTF vs non-SGTF positives.Results15,166(0.98%) of 1,553,687 swabs were PCR-positive, 8,545(56%) with three genes detected and 3,531(23%) SGTF. SGTF comprised an increasing, and triple-gene positives a decreasing, percentage of infections from late-November in most UK regions/countries, e.g. from 15% to 38% to 81% over 1.5 months in London. SGTF Ct values correspondingly declined substantially to similar levels to triple-gene positives. Population-level SGTF positivity remained low (<0.25%) in all regions/countries until late-November, when marked increases with and without self-reported symptoms occurred in southern England (to 1.5-3%), despite stable rates of non-SGTF cases. SGTF positivity rates increased on average 6% more rapidly than rates of non-SGTF positives (95% CI 4-9%) supporting addition rather than replacement with B.1.1.7/VOC202012/01. Excess growth rates for SGTF vs non-SGTF positives were similar in those up to high school age (5% (1-8%)) and older individuals (6% (4-9%)).ConclusionsDirect population-representative estimates show that the B.1.1.7/VOC202012/01 SARS-CoV-2 variant leads to higher infection rates, but does not seem particularly adapted to any age group.

Initial real world evidence for lower viral load of individuals who have been vaccinated by BNT162b2

“…In total, we had 16,297 positive tests and we traced the average Ct values stratified to two age groups: individuals over 60 (5,317 positive tests) and individuals between 40 to 60 years old (10,980 positive tests). Consistent with previous studies ( 6 ), we did not observe substantially higher viral load due to the emergence of B.1.1.7 in Israel.…”

“…Third, we assumed that the emerging variants distribute equally among age groups. We believe that this assumption is a valid approximation since by mid January 50% of the thousands of daily cases had this strain, meaning that these variants were widely distributed in Israel by late January and that previous studies did not find differences in viral load between B.1.1.7 and wild type SARS-CoV-2 ( 6 ). Fourth, it has been estimated that 33% of all cases in Israel are due to household transmission.…”

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

“…In infected individuals, a small but significant decrease in Ct values in G614 compared to D614 infections in the UK demonstrated increased viral load for variants carrying D614G (Volz, Hill, et al, 2021). For B.1.1.7, early analysis using the number of mapped sequencing reads or Ct values as proxies for viral load suggested an increased viral burden associated with B.1.1.7 infection (Golubchik et al, 2021;Kidd et al, 2020) but more recent reports show no such association at either the population level or longitudinally in individuals (Kissler et al, 2021;Walker et al, 2021). The more recent reports and our data suggest there is no clear replicative advantage for B.1.1.7 in vitro or at the population level.…”

“…The copyright holder for this this version posted February 24, 2021. ; https://doi.org/10.1101/2021.02.24.432576 doi: bioRxiv preprint Walker et al, 2021). Another recent study showed similar peak viral burden but an increased duration of infection with B.1.1.7 infection, albeit with a small sample size (Kissler et al, 2021).…”

An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

“…Estimates suggest increased transmissibility and disease severity. [17][18][19][20] The lineage carries several mutations of immunologic significance, including N501Y located in the receptor-binding domain (RBD), a key neutralising antibody target; deletions in the N-terminal domain at residues 69/70, associated with viral escape in the immunocompromised and S-gene target failure (SGTF) in PCR assays; and a deletion at residue 144 resulting in decreased monoclonal antibody binding. 21 Reinfection rates following natural infection have not been shown to be higher in studies using SGTF as a proxy for B.1.1.7, 20,22 even though variably decreased sensitivity to neutralisation by monoclonal antibodies, convalescent plasma and sera from vaccinated individuals has been observed in vitro for B.1.1.7.…”