Following an announcement made at the Downing Street press conference that the new UK variant, B.1.1.7, may be associated with higher mortality, a paper has been published by the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG).
Dr David Strain, Senior Clinical Lecturer, University of Exeter, said:
“The data came from a the government’s New and Emerging Respiratory Virus Threats Advisory Group (or Nervtag) based on a separate studies in Imperial, LSHTM, PHE and here at Exeter. Each showed slightly different outcomes, with the highest estimate being 91%, although from a region in the country with the lowest prevalence of this new variant. Other regions in the country showed no difference at all. NERVTAG produced a model for the country with an estimated mean of about 30%.
“The most concerning comment is that the in-hospital mortality is the same but the total mortality is 30% higher.
“To look at Sir Patrick’s figures in detail that means:
“This new variant is 50-70% more infectious, therefore more people are catching this variant. That is not covered in these figures which are just talking about mortality once you have the virus.
“Extrapolating from the CSO’s Figures, 13 out 1000 people with a new variant die compared to 10 out of 1000 people with the old variant. But he also said the percentage death in hospital was the same. Let’s say for the sake of argument in hospital mortality is 10% with both variants, that must mean 130 people with the new variant must have been hospitalized as opposed to 100 with the original strain. This could account for why hospitals have 79% more patients now compare to the peak of the first wave. I stress these numbers are purely as an example extrapolated from Patrick Vallance’s figures.
“This does assume that the figures are accurate. Across all 4 studies that NERVTAG considered, that only had 8% of the total deaths since the new variant was identified, and given the different geographies demographics, relative frequencies etc. in the different populations studied (important to say that the worst figures were in the region with the lowest prevalence of the new variant, thus 1 or 2 cases either way could have a huge impact on percentages) we need much more data before we draw too many conclusions.
“A new more infectious variant, with potentially greater mortality highlights the importance of the current lockdown and that we all continue to maintain 2m distance, wear our masks even after our first vaccine.”
Dr Leon Danon, Associate Professor in Infectious Disease Modelling and Data Analytics, University of Bristol, said:
“My group at the Universities of Exeter and Bristol looked at people tested in the community (Pillar 2 data). We performed a matched cohort study, where a person infected with the new UK variant was compared to a similar person (similar age, tested at a similar time, living in a similar area) infected with the old strain.
“We calculated the additional risk of death imparted by the new UK variant. We found that people infected with the new UK variant have an risk of death that increased by 50% – 170%. This means that, from our estimates, out of 1000 people infected with the new variant two would be expected to sadly die, compared with 1 person infected with the old variant.
“Other groups using different approaches came up with slightly different numbers, but most suggest there is an increased risk of death with the new UK variant. The estimates depend on how well a given method is able to capture other, known risk factors. Ours is at the higher end of those estimates. The confidence intervals from the studies from other groups overlap with ours so the real answer is probably somewhere in the middle.”
Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:
“Various things can affect overall clinical outcomes in COVID-19, including ethnicity, age, sex, pre-existing comorbidities, plus the increasing stress on NHS teams.
“The data and interpretation presented verbally by Patrick Vallance and the accompanying NERVTAG document included relatively low numbers of VOC (variant of concern) cases, so the example he gave might be potentially subject to large changes later – where he described the mortality for a ~60-year old men potentially rising from 10 to 13 per 1000 due to the new UK variant virus.
“The VOC/non-VOC patient case mix (with different patterns of comorbidities and ethnicities) was not given for the patients analysed.
“We know that the mortality for people with such pre-existing comorbidities in winter is generally increased anyway in the colder months – regardless of the virus, e.g. patients with heart disease are more likely to experience exacerbations in the winter because the cold will increase the demands on the heart making heart attacks more likely: https://www.sciencedirect.com/science/article/pii/S0735109799001370
“So the fact that you see more winter mortality, particularly in patients with various comorbidities, may not be that surprising – and then you have to add any impact of the UK variant virus to this.
“But what this means is that assigning any increased mortality in COVID-19 patients to just this UK variant virus without considering the overall increased baseline winter mortality related to patients’ pre-existing comorbidities might be misleading – the difference between 10 and 13 out of 1000 is not great – and Jan/Feb are generally the coldest months in winter.
“However, despite all of this, the public health message is still the same: that we should all continue to reduce our social contacts and try to remain at home, to reduce the spread of the virus – whilst the vaccination program rolls out to protect the most vulnerable.”
Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:
“This is sobering news. The variant of the coronavirus which has swept across the UK is not only more transmissible, but appears to be 30-40% more lethal than those which we have previously experienced.
“Initial research indicates that the mutations found in the virus spike protein aren’t affecting the way antibodies respond to the presence of the coronavirus, blocking the entry of the virus into human cells.
“We don’t yet know whether the mutations in the spike protein or other parts of the coronavirus affect the ability of antibodies to tag the virus for destruction by white blood cells. Neither do we know the extent to which T cell immunity is affected.
“What we do know is that the variant is more able to bind to our cells, which could provoke a stronger overreaction by the immune system, which causes the worst disease, and can be fatal.”
Prof Rowland Kao, the Sir Timothy O’Shea Professor of Veterinary Epidemiology and Data Science, University of Edinburgh, said:
“The evidence presented suggests that a higher proportion of individuals who become infected with the new variant then go on to die (an increase from 10 in 1,000 to 13 or 14 in 1,000). These results are from studies that compare individuals known to have been infected with the new variant and contrasting them with individuals infected with the original virus, while correcting for factors that might influence mortality such as age, location and ethnicity. The briefing also says that the increase in deaths is a result of more individuals becoming severely infected becoming hospitalised, rather than more hospitalisations resulting in death. As such, it would appear that the new variant is also responsible of the increased, unexpectedly high burdens in hospitals seen especially around London. Thus while the recent results showing declining case numbers is good news, and suggest that the variant is controllable via existing measures, these results on deaths imply that burden in hospitals will continue to be high requiring a more prolonged period of restrictions.”
Prof Ian Jones, Professor of Virology, University of Reading, said:
“The NERVTAG report supporting the enhanced death rate attributed to variant B1.1.7 is at pains to stress that the data is limited and the conclusions preliminary. However, an increased case fatality rate is certainly possible with a virus that has upped its game in transmission. But grim as it sounds, whether the fatality rate is 1% or 1.3% doesn’t really change the fact that for a minority of people this is a very dangerous virus that is best avoided. That is achieved by strict adherence to lockdown measures and a willingness to take the vaccine as soon as it is offered. That the variant is as susceptible to vaccine induced immunity as the parental virus means its circulation should fall as vaccine coverage increases providing hope that the threat it poses is limited overall.”
Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, said:
“The mutant SARS-CoV-2 variant may be more deadly than the original virus. This variant is also more transmissible and accounts for the surge of infections in the UK. The published report from the government’s New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) suggests that the new variant may increase the risk of death by 30 per cent compared to the original virus. As highlighted by Patrick Vallance in today’s press conference, this means that for 60 year-olds, 13 in 1000 might die compared with 10 in 1000 for old variant. This increase in the rate of death appears across all age groups. However, the available data is based on a limited subset of the total deaths from COVID-19 with data on the type of virus in only 8% of deaths. Importantly the report highlights that there is currently no indication of increased risk of hospitalisation in individuals infected with the variant virus which would be expected if infection is more severe. This could be due to lags in the availability of data. We need more information before jumping to firm conclusions.
“It’s important to stress that recent laboratory studies have confirmed that the UK variant (B.1.1.7) can be blocked from infecting cells by antibodies from individuals vaccinated with the Pfizer/BioNTech vaccine. Artificially engineered viruses carrying similar changes in the spike protein to those observed in the UK variant are able to be blocked by antibodies from individuals who have recovered from infection with the original virus. These studies provide confidence that vaccination will protect against disease caused by infection with the UK variant. The other virus variants identified in South Africa and Brazil are more worrying as they carry more changes in the spike protein of the virus. Laboratory studies suggest that these changes may allow the South African and Brazilian virus variants to escape immune protection and this could affect the efficacy of current vaccines as well as increase the chances that previously infected individuals could be re-infected. It is important that we now determine the neutralising ability of antibodies against virus variants generated in response to vaccination and study the immune response in individuals infected with virus variants.”
Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:
“The paper from NERVTAG just released gives the data behind the Prime Minister’s statement today that the B.1.1.7 variant may indeed be more lethal than prior variants. This is disappointing especially as initial analyses suggested that it was not more lethal. The conclusion about this probable increased lethality comes from analyses made by several different groups, though working with essentially the same data. There is quite a bit of difference in the estimated increased risk of death between the different analyses, though most but not all show increased risk of death.
“Although we have yet to see the full reports of these different analyses, I give more weight to the PHE Retrospective matched cohort study (updated analysis 19/01). Cohort studies are generally considered to be higher up the quality of evidence pyramid than most other observational studies. This PHE analysis reported the Relative risk of death in SGTF cases vs non-SGTF cases (SGTF is Spike gene target failure and is a good surrogate for the new variant) within 28 days of a +ve result of 1.65 (95% confidence intervals 1.21-2.25). Essentially this would mean that the new variant was 65% more likely to lead to death within 28 days than any other variant. Other analyses have suggested a lower but still generally increased risk.
“This is a really disappointing finding and will certainly have implications for how we manage the epidemic over coming months. Nevertheless we are still likely to see deaths start to decline in the coming weeks given the rapid decline in new cases.”
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