A preprint, an unpublished non-peer reviewed paper from the REACT-2 programme, looked at prevalence of antibody positivity to SARS-CoV-2 in 154,000 people between 26 January and 8 February 2021 (during the vaccine roll-out).
This Roundup accompanied an SMC Briefing.
Prof Peter Openshaw, Professor of Experimental Medicine, Imperial College London, said:
“The stand-out result here with respect to the antibodies measured on the finger-prick home kits is that there’s fewer positive results in older people who had only had one dose of the Pfizer vaccine (94.7% in those under 30; 73.7% at 60 to 64 years; 34.7% in those 80 and over).
“However, this test does not determine the exact level of antibody but gives a positive or negative readout on the device. JCVI previously noted that in Pfizer’s clinical trial, protection against COVID was very high (89%) between 14 and 21 days after vaccination despite low levels of antibodies measured at that time. Thus, early antibody responses are not a reliable indicator of protection against disease. This is especially true of a rapid, convenient but relatively insensitive home kit.
“It’s important to note that there is no clear downward trend in antibody positivity with time after vaccination. Those who had COVID and then got vaccine had really high levels of positivity on the antibody test, as expected.
“Another important finding is that vaccine confidence was remarkably high but dependent on ethnicity (White, 92.6%; Black 72.5%) and some other factors (those under 50 were more sceptical than older people, and those in London more sceptical than those elsewhere). Still, even 72.5% is very encouraging and much better even than the average in some other European countries. Many of those still uncertain were wanting to wait and see, rather than expressing outright opposition to vaccination.”
Prof Richard Tedder, Senior Research Investigator in Medical Virology, Imperial College London, said:
“I have a potential conflict of interest holding patents on laboratory based assays developed at Imperial College for the detection and quantification of antibody to SARS CoV 2 and being a colleague myself at Imperial.
“That said there remain significant issues relating to self administered assays exemplified by the lateral flow arena, both in terms of sensitivity and specificity. One notes that some 10% of the returned results were considered invalid. Quality assurance remains a significant issue for self administered testing. My preference is for self administered sampling with referral of the sample to a laboratory able to conduct the testing with an option for reference confirmation and quantification if required. In addition I am concerned about reliance on the new Abbott assay which may not be specific at the lowest range of reporting. This is a matter of concern as one is needing to look for and confirm specificity in those population derived samples which are at the lowest level of reactivity for detectable antibody following asymptomatic infections. Nevertheless the authors are to be congratulated on their aspirations.”
Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:
“These new REACT-2 results are very interesting. REACT-2 is not to be confused with the regular REACT-1 survey – both are run from Imperial College, but REACT-1 tests people for a current infection with the virus that causes Covid-19, while REACT-2 tests for the presence of antibodies to parts of that virus. So someone will test positive in REACT-2 if they have either had a previous infection with the virus, and their immune system has produced antibodies to fight that infection that can still be detected in their blood, or if they have been vaccinated, and their body has produced antibodies that can be detected. The people who were tested were chosen to be a reasonably representative sample of community population of England, and appropriate adjustments were made to allow for imbalances in the sample that might have arisen, so the results should give a pretty accurate picture of the status of the English population in relation to these antibodies. The antibody test that was used cannot distinguish antibodies resulting from an infection from antibodies resulting from vaccination – but in this survey, the people who were tested were also asked to complete a questionnaire. They were asked various questions about their personal characteristics (gender, age, ethnicity, their type of work, the level of deprivation of the area where they live, and more), about whether they had had a previous Covid infection, whether they had been vaccinated, and when, which vaccine they had had, and how many doses, and also whether they had accepted the vaccine, or would accept it if and when it is offered to them. So the researchers can relate whether people have antibodies in their blood to all these characteristics, and that throws some light on the way in which vaccines can produce antibodies to fight the virus. The results also throw a certain amount of light on people’s confidence in the virus.
“However, many of these findings in relation to vaccination are rather tentative. That’s because the tests in this REACT-2 round were done between 26 January and 8 February this year. It takes some time – roughly three weeks – after vaccination until antibodies become clearly detectable in the blood. Overall, in this round about 18,000 people who had been vaccinated with at least one dose were tested for antibodies, along with almost 137,000 people who had not (yet) been vaccinated at all. So the findings about people who had not been vaccinated are statistically considerably more reliable, just because there were far more of them. Also, because the Pfizer/BioNTech vaccine came into use in England some time before the Oxford/AstraZeneca vaccine, almost all the people who had been vaccinated at least three weeks before they were tested – sufficient time for the antibodies to become detectable – had had the Pfizer/BioNTech vaccine rather than Oxford/AstraZeneca. (Only 182 people in the REACT-2 sample had had any dose of the Oxfor/AstraZeneca vaccine more than three weeks before their antibody test.) So the researchers simply cannot yet provide data on how likely the Oxford/AstraZeneca vaccine is to produce antibodies in the blood. All this will change in further REACT-2 rounds as more and more people are vaccinated.
“The last REACT-2 round in early November estimated that between 5.4% and 5.7% of the English community population had antibodies. Since vaccination had not started then, apart from a few people in vaccine trials, those antibodies would all have arisen from previous infection. In the latest round, just considering the people who had not been vaccinated yet, the estimate is that between 9.6% and 10.0% have antibodies. That’s a very big increase, caused by the very high peak in new infections during the autumn and winter – and since infections are still fairly high, those percentages in unvaccinated people will continue to increase. As in previous rounds, the prevalence of antibodies does differ quite considerably between different population groups. Prevalence of antibodies is particularly high in London, in people of Black and Asian ethnicity compared to White people, in people living in more deprived areas, and in people working in health care and care home roles – but none of that is surprising, because we already know that those groups have had relatively high rates of infection.
“Given the national vaccination priorities, it’s not surprising that most of those who had already been vaccinated were older (predominantly 80 or older), or were healthcare or care home workers. 93% of those aged 80+ had received at least one vaccine dose, and 67% of healthcare and care home workers. At the time these people were tested for antibodies, the percentage of those aged 70 to 79 who had been vaccinated was lower, 34%, because that age group were offered vaccination later than those aged 80+ and health and care home workers – and the vaccination rates for other groups were obviously smaller still. That will change in future.
“The effects of vaccination on antibodies were pretty clear, but there are some important differences between groups. Overall, in people who had already received two doses of the Pfizer/BioNTech vaccine at least three weeks earlier, 91% would test positive for antibodies. There’s some statistical uncertainty about that, because the numbers of people involved were not huge – just 971 people in the sample had had two doses – and the interval showing that uncertainty runs from 89% to 97%. But that’s a good indicator that, after two doses, the protection against illness is likely to be high. This study didn’t measure whether people actually got ill, only the antibody response, so it cannot directly tell us about the effect of vaccination on suppressing Covid illness. But the signs are good for people who have had two doses of this vaccine.
“The position in people who had had only one dose of the Pfizer/BioNTech vaccine is also favourable, but not quite so favourable, particularly in the oldest age groups. The prevalence of having antibodies 21 days or more after just one dose did vary with age. It was estimated as about 95% in those aged 18-29, and was still reasonably high at 77% in the 50-59 group and 71% for those aged 60-69 – but for the 70-79 group it was lower, 49%, and lower still, 35%, for those aged 80 and over. I think this is unlikely to be simply a matter that the older people just have to wait longer after the first dose for the antibody protection to grow to a high level. That’s because the percentage with antibodies appears to stop rising after three weeks after the dose – the REACT-2 researchers report that the rate appears to ‘plateau after four to five weeks in all age groups’.
“There was a much smaller effect of age on antibody positivity in people who had had two doses, and for them, 88% of those aged 80 and over had antibodies. Because of that, I think it’s likely that those antibody rates in older people after one dose will increase considerably after their second dose, but this does indicate the importance of a second dose in older people. (And, as the report points out, there are other aspects of immunity, including those involving T-cells, than immunity involving antibodies. The immune response is a complicated business.) Another very interesting finding was that, in people who had previously had an infection before they were vaccinated, one dose of the vaccine brought them up to a very good prevalence of having antibodies, even if they were in the oldest age groups.
“The results on vaccine confidence were broadly similar to what has been found in other data. Confidence was generally very high, with an estimated 92% of people, overall, saying that they had accepted the offer of vaccination or would accept it when it arrived. This rate was higher in older people, in men compared to women, and in those of White ethnicity compared to other ethnic groups. But even in the groups with the lowest percentage saying they have accepted or would accept the vaccine, those percentages were higher than I’ve seen in some other research. That’s encouraging – but I do wonder how typical the people tested in this survey are of the whole population in this respect. To be tested in the survey, people have to agree to take part. It’s plausible, perhaps, that people who would agree to prick their finger and put a (very small) blood sample on a testing device would be a bit more likely to agree to be vaccinated than the general population – but these survey results can’t tell us whether this suspicion is correct. We’ll know more in later rounds of REACT-2, as vaccines are rolled out across more population groups.”
Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:
“REACT2 continues this week’s amazing treasure trove of findings about the UK’s roll-out of the world’s first mRNA vaccine: Pfizer/BioNTech.
“Adherent to the advice of UK’s Chief Medical Officers, Scotland administered few 2nd doses of the Pfizer/BioNTech vaccine. On Monday, a leading biostatistical and public health team reported that, Scotland-wide, Pfizer/BioNTech’s vaccine effectiveness (VE) for reducing COVID-19 hospitalizations peaked at 85% (95% CI: 76 to 91) during 28-34 days after Dose 1; thereafter, VE reduced to 66% (95% CI: 57 to 76) at 35+ days after Dose 1.
“In England, over a third of those who received their first Pfizer/BioNTech vaccine before 4 January 2021, received their 2nd dose, mostly in the week of 4-10 January. This major exercise of clinical discretion has enabled REACT2 to report impressively high IgG positivity after 2nd Pfizer/BioNTech dose in 971 participants: namely, 95% IgG positive in 18-79 year olds who received their 2nd dose (408/428, 95% CI: 93 to 97%) and 88% in those aged 80+ years (477/543, 95% CI: 85 to 90%).
“By contrast, IgG positivity decreased markedly by age-group for 3011 participants who had received a single Pfizer/BioNTech dose more than 21 days before survey-date. Positivity decreased from 95% in 225 participants aged 18-29 years (95% CI: 91 to 97%) to 77% in 599 participants aged 50-59 years (95% CI: 74 to 80%) and 49% in 304 participants aged 70-79 years (95% CI: 43 to 54%) to just 35% in 845 single dose recipients aged 80+ years (95% CI: 31% to 38%).
“Good other news from REACT2 is that IgG positivity is high, around 90%, from 21 days after a single dose of Pfizer/BioNTech vaccine for those who have had suspected or confirmed COVID.
“Amid the good news, an alert: that prevalence of vaccine-induced IgG antibodies (but not necessarily T-cell immunity) decreases with age and with time since administration of a single dose. Since the field-work for REACT2 was undertaken from 26 January to 8 February 2021, the maximum follow-up after a single Pfizer/BioNTech dose on 14th December 2020 is barely 8 weeks and many – or most – in England who had received their 1st dose pre-Christmas may have had their 2nd, despite the Chief Medical Officers’ advice at Hogmanay.
“Hence, the next round of REACT2 will be as eagerly awaited to discover the impact of delayed 2nd doses in recovering decayed IgG antibody levels and for initial findings on IgG positivity after a single dose of the Oxford/AstraZeneca vaccine which began to be administered on/after 4 January 2021.
“In summary: another magnificent report by England’s munificent team of REACT scientists.”
Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:
“These latest REACT data map the antibody response to COVID-19 across different age and ethnicity demographics. They also monitor the antibody response in groups who’ve had the Pfizer-BioNTech vaccine BNT162b2. These are robust data with interesting and meaningful conclusions.
“It is of concern that in studies of individuals aged 70 years or over, a single dose of the vaccine was associated with substantially lower levels of antibodies than in younger age groups, or in those who had had COVID-19 prior to vaccination. This shows that with this vaccine, the immune response is much greater in individuals who have been exposed twice, either through a prior infection or through double vaccination.
“In this older age group, the already lower antibody levels peaked at 5 weeks after receiving the first dose, then declined. However, after the second dose, levels were comparable to those in younger age groups. These data highlight the importance of receiving the second dose, particularly in the most vulnerable age groups and imply that extending the gap between injections to 12 weeks may not be the best way to deliver the best immune response in people over 70.”
Prof Marian Knight, Professor of Maternal and Child Population Health, Nuffield Department of Population Health, University of Oxford, said:
“This robust and comprehensive study provides further positive news on the impact of the vaccination programme on antibody levels. The large size of the study provides additional reassurance that confidence in the vaccine is high across most population groups. It is, nonetheless, worrying that participants are reporting concerns over planned or current pregnancy and fertility. Guidance from the Royal College of Obstetricians and Gynaecologists is clear that women trying to become pregnant do not need to avoid pregnancy after vaccination and women should be reassured that there is no evidence to suggest that COVID-19 vaccines will affect fertility.
“These concerns do emphasise further the urgent need for information about vaccination in pregnancy. Vaccine trials including pregnant women have still not started and there is no comprehensive information available about pregnancy outcomes in women who are receiving the vaccine as part of the current rollout. While there are no reasons to suspect safety concerns about vaccination in pregnancy, better evidence is needed to enable pregnant women to make an informed choice about whether to receive a vaccine.”
Preprint (not a paper): ‘REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England’ by Helen Ward et al. was posted online at 00:01 UK time on Thursday 25 February 2021. This work is not peer-reviewed.
All our previous output on this subject can be seen at this weblink:
Prof Peter Openshaw: “I’m at Imperial College London. I have been on several scientific advisory boards that have paid fees to Imperial, including for GSK, Pfizer, Janssen and Nestle. I have not consulted in relation to the published work.”
Prof Richard Tedder: “I have a potential conflict of interest holding patents on laboratory based assays developed at Imperial College for the detection and quantification of antibody to SARS CoV 2 and being a colleague myself at Imperial.”
Prof Kevin McConway: “I am a Trustee of the SMC and a member of its Advisory Committee. I am also a member of the Public Data Advisory Group, which provides expert advice to the Cabinet Office on aspects of public understanding of data during the pandemic. My quote above is in my capacity as an independent professional statistician.”
Prof Sheila Bird: “SMB is Honorary Professor at Edinburgh University’s College of Medicine and Veterinary Medicine and, until recently, Visiting Professor at Strathclyde University’s Department of Mathematics and Statistics but took no part in the analyses reported from Scotland. She is a member of the Royal Statistical Society’s cOVID-19 Taskforce; and called for randomized evaluation of the UK’s public-interest decision to delay the second dose of the world’s first mRNA vaccine.”
Dr Simon Clarke: “None.”
Prof Marian Knight: “I lead the national urgent public health study of Covid-19 in pregnancy.”