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Two observational studies, published in The Lancet Infectious Diseases and The Lancet Public Health, suggest that the COVID-19 variant B.1.1.7 is more transmissible, but does not increase disease severity.
Comment updated 13/04/2021: Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said: (onThe Lancet Infectious Diseases paper)
“It’s a relief that my former UCL/UCLH colleagues have finally debunked the idea that the B.1.1.7 variant causes more severe disease.
“Their study had two key advantages: they had access to individual patient datasets so they could characterise and control for individual level comorbidity variation between B.1.1.7 and non-B.1.1.7 infections; and they used full genome sequencing (on an Illumina MiSeq) to identify the B.1.1.7 variant infections.
“The lack of individual patient level comorbidity data to control for confounding between B.1.1.7 variant and non-B.1.1.7 variant cases, together with the use of the S-gene target failure (SGTF) as a surrogate marker of the B.1.1.7 variant, could potentially give rise to misleading results:
https://www.nature.com/articles/s41586-021-03426-1
“Not all labs would have used an S-gene target for SARS-CoV-2 PCR testing (e.g. our lab does not), so there could have been B.1.1.7 cases that would have been missed using this SGTF criteria, who may have had milder symptoms that would have reduced the overall clinical severity in B.1.1.7 cases. The use of full-genome sequencing for individual patient samples to identify all true B.1.1.7 cases for comparison is a much more reliable approach.
However, this PHE study covering an earlier timeline, also using the SGTF marker for the B.1.1.7 Kent variant, also found no significant difference in mortality between VOC/non-VOC cases – and these were not all hospitalised cases:
“The 28-day case fatality was assessed for variant cases and comparator cases. Analysis was restricted to 2,700 cases with a full 28 days elapsed since the specimen date. Among variant cases, 12 of 1,340 (0.89%) variant cases died within 28 days of their specimen date compared with 10 of 1,360 (0.73%) wild-type comparator cases; this difference was not signfiicant (sic) (Odds ratio:1.21, p=0.65).”
Dr Nicholas Davies, Evolutionary biologist and Epidemiologist, London School of Hygiene and Tropical Medicine:
“The study by Frampton et al. appears sound and well-conducted, and is compatible with our current understanding of B.1.1.7 severity. Similarly to this new paper, numerous other studies have been unable to clearly resolve a difference in: mortality among hospitalised patients (#18 and #21 in 1); ICU admission among hospitalised patients (#18 in 1); or mortality among ICU patients (2), when comparing patients infected with B.1.1.7 to those infected with pre-existing variants of SARS-CoV-2.
“In my view, however, the accompanying comment piece and press release may present an incomplete picture of the scientific evidence collected on B.1.1.7 severity to date. The new study does not refute existing evidence—amassed by community-based studies in England (2, 3, 4, 5, #14 and #15 in 1), Scotland (#17 in 1), and Denmark (6)—that B.1.1.7 infection is associated with a higher overall risk of mortality, hospital admission, and ICU admission among individuals who test positive for SARS-CoV-2 in the community. This study focuses on outcomes among a different group of people, namely individuals who are already hospitalised with COVID-19. Overall, the evidence suggests that B.1.1.7 is more likely to land you in the hospital than pre-existing variants of SARS-CoV-2, but once in the hospital there are no substantial differences in outcomes—or at least none that are statistically resolvable for now, given the limitation of low sample sizes. While there is still much to learn about the severity of B.1.1.7, and additional studies—especially outside the U.K.—are sorely needed, any new piece of evidence needs to be properly contextualised with what we already know.”
1 NERVTAG update note on B.1.1.7 severity
2 ‘Analysis of severe outcomes associated with the SARS-CoV-2 Variant of Concern 202012/01 in England using ICNARC Case Mix Programme and QResearch databases’ by Martina Patone et al. is a preprint on MedRxiv
https://doi.org/10.1101/2021.03.11.21253364
3 Davies, N.G., Jarvis, C.I., CMMID COVID-19 Working Group. et al. Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature (2021). https://doi.org/10.1038/s41586-021-03426-1
4 Challen R, Brooks-Pollock E, Read J M, Dyson L, Tsaneva-Atanasova K, Danon L et al. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study
doi:10.1136/bmj.n579
5 Daniel J Grint et al. Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February. Eurosurveillance
https://doi.org/10.2807/1560-7917.ES.2021.26.11.2100256
6 ‘Increased Risk of Hospitalisation Associated with Infection with SARS-CoV-2 Lineage B.1.1.7 in Denmark’ by Petr Bager et al is a preprint on the Preprints with The Lancet server
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3792894
‘Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study’ by Dan Frampton et al. was published in The Lancet Infectious Diseases at 23:30 UK time Monday 12 April.
https://doi.org/10.1016/S1473-3099(21)00170-5
‘Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study’ by Mark S Graham et al. was published in The Lancet Public Health at 23:30 UK time Monday 12 April.
https://doi.org/10.1016/S2468-2667(21)00055-4
All our previous output on this subject can be seen at this weblink:
www.sciencemediacentre.org/tag/covid-19
Declared interests
Dr Nicholas Davies: “Dr Nicholas Davies is author of one of the studies cited in his comment.”
None others received.