The Office for National Statistics (ONS) have released data from their COVID-19 Infection Survey on antibodies for January 2021.
Prof Eleanor Riley, Professor of Immunology and Infectious Disease at the University of Edinburgh, said:
“I am struggling to see the value of these data, at least as currently presented. We are able to monitor the progress of the UK epidemic through the daily numbers of positive tests, the ONS infection (swab) data and through remote data collection (such as through the Zoe C-19 app). The additional value of measuring antibodies would be to identify anyone who has ever been infected, the assumption being that people develop antibodies after infection (whether or not that infection was formally diagnosed at the time) and remain antibody positive for a significant period of time after they clear the virus. One would expect, therefore, that antibody positivity rates in the population would increase steadily over time as the proportion of the population that has ever been infected increases.
“What we are seeing in these data, however, is that antibody positivity rates fluctuate over time, increasing in the immediate aftermath of an increase in cases but then falling again as cases fall. This suggests that the antibodies that are being measured are not very long lasting. It is not clear to me why this is the case as other studies, including a recent PHE study, suggest that antibodies persist for many months.
“It would be helpful if the ONS could publish some of the underlying data on which the antibody prevalence estimates are based. How sensitive is the assay? Is it sensitive enough for this purpose or are better assays needed? How is positivity defined? Have individuals been followed over time to see how long their antibodies persist? Presenting the data as the cumulative proportion of people in the survey who have ever tested positive would give us a much better idea of the proportion of the population who have been infected to date.”
Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:
“The regular (monthly) data from the ONS Infection Survey provide really the only way of estimating the percentage of people in the populations of the UK countries who would test positive for antibodies to SARS-CoV-2, the virus that causes Covid-19. Antibody testing differs from the tests (PCR and lateral flow testing) that indicate whether someone has a current infection with the virus. Instead, a positive test for antibodies indicates that the person’s immune system has reacted to an infection with the virus, or a vaccination, at some time in the past. The survey tests a reasonably representative sample of the community population aged 16 and over for the presence of antibodies. (It therefore omits people who live in communal places such as care homes or prisons, but that’s a very small proportion of the whole population. More importantly, it does not include under 16s.) There is no large-scale regular testing for antibodies of the population more generally, unlike the position with swab tests to indicate whether someone has a current infection. Imperial College’s REACT-2 survey does also test a representative sample of people for antibodies, but only in England, and it has not reported any results since October.
“Probably the most striking finding in the latest results is the very large growth in antibody positivity since the summer. The number of people who would test positive in England more than doubled between August and December 2020. In Wales, the number more than tripled. (In fact, the December estimate is close to three and a half times the August figure). The increase in Northern Ireland is not quite so big as England, and there is considerable statistical uncertainty about the numbers there because the number of people tested is not so large. There is also quite a lot of uncertainty about the Scottish figures, and they go back only to October, because the survey started later there and the number of people tested was initially not so large. It’s not at all surprising that the numbers have gone up so much in England and Wales, given the large second wave of infections that began after the summer and is continuing. Numbers testing positive for antibodies will increase over time as more people are infected and their immune systems respond by producing antibodies. But the level of antibodies in someone’s blood after an infection will also tend naturally to decrease over time – a process called ‘antibody fading’. (This does not necessarily mean that the person’s immunity to the virus has gone away – there are other mechanisms of immunity too. But I’m no immunologist and cannot speak authoritatively about that.)
“Just considering England and Wales, the estimated number of people who would test positive for antibodies increased by over three million between September and December. There’s some statistical uncertainty about that figure, since it’s based on survey results, but it’s undeniably huge. Almost all that increase will have been from new infections, because only a very small proportion of people would have got antibodies from vaccinations over that time. (That’s because only a very small proportion of the population would have been vaccinated in vaccine trials, and the roll-out of the mass vaccination programme didn’t happen until right at the end of that period covered by the data and had not yet vaccinated many.) And the true number of new infections must have been higher – some people who were infected in the first wave, and who might still have had detectable antibodies in September that would have faded by December, would reduce the December number a bit, and none of these figures include infections in children under 16. But the number of new confirmed Covid-19 cases in England and Wales between mid-September and mid-November, as shown on the dashboard at coronavirus.data.gov.uk, is only about one and a half million. Most of the confirmed cases would be people who had symptoms of some sort, as well as testing positive on a swab test. So we’ve got over three million new infections on the evidence from the antibody survey, possibly well over three million if under 16s are taken into account, and less that half that number in confirmed cases. This is another demonstration of the considerable numbers who are infected with the virus but don’t show symptoms, and that’s one reason why it’s not been easy to break the chains of infection and why vaccination is so important.
“Though ONS rightly point out that there’s quite a lot of uncertainty in the estimates of antibody positivity in the English regions, because the number of people tested in a single region is bound to be considerably smaller than in the whole country, there’s some pretty clear evidence of differences between regions in antibody positivity. The highest positivity rates are in the two regions in the North (North West, and Yorkshire and the Humber) where infections were running at a relatively high level throughout late summer and most of the autumn, and also in London, which was hard hit in the first wave (and a lot of people infected then will still test positive for antibodies) and where cases started rising fast in late autumn before some other regions. In those three regions, roughly one person in six would test positive for antibodies. The positivity estimate is perhaps rather lower in the North East and in the two Midlands regions, around one in seven or eight, though the statistical variability means that we can’t really be sure that it’s lower there than in the other northern regions and London. But it’s clearly lower in the regions of the South other than London – roughly one in twelve would test positive in the South East and the East of England, and one in twenty in the South West. Again this simply reflects what’s already known about the path of the pandemic there – infections were relatively low in all those regions in the first wave, and though they rose alarmingly in much of the South East and East in late autumn, that wouldn’t have produced a huge level of antibody positivity by the December estimate, compared to other regions. In the South West, though there were worrying increases in infection during December, the level of infection there is still relatively low compared to most other parts of England.
“These monthly figures may be the last time that antibody testing results can be easily used to give some indication of how many people have previously been infected with the virus. That’s because, as vaccinations are rolled out, more and more people will test positive for antibodies because of the immunity built up by the vaccine. As far as I’m aware, these antibody tests can’t distinguish between antibodies arising from a natural infection and antibodies arising from a vaccination. But that doesn’t mean that antibody testing will become useless. We’ll still need to know whether antibody levels from infection and vaccination are getting to the level where herd immunity becomes important, and also to check on antibody fading.”
Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, said:
“This study shows that infection with the SARS-CoV-2 virus is much more widespread in the UK than previously realised with around 1 in 10 people estimated to have been infected by December 2020. Measuring antibodies in the blood is an indication of previous infection but doesn’t indicate when that infection took place. Significant increases in antibody positivity where observed between November 2020 and December 2020 in England, Wales and Scotland although these are estimates with large variations including substantial differences between regions in England. This ONS data is based on a survey of community infections in private households and excludes infections reported in hospitals, care homes and other institutional settings. Blood samples were analysed for IgG antibodies to the SARS-CoV-2 trimeric spike protein using an ELISA test. The implications are that infection rates increased significantly between November and December. This raises some important questions concerning the possible impact of the UK variant virus on infection rates – this variant is more transmissible and may account for the increased levels of infection as detected by antibodies. It is also interesting from the perspective of the vaccine. We are still not sure about the impact of vaccination on the levels and duration of protective immunity in those previously infected with SARS-CoV-2.”
All our previous output on this subject can be seen at this weblink:
Prof Eleanor Riley: “No conflicts of interest.”
Prof Kevin McConway: “I am a Trustee of the SMC and a member of the Advisory Committee, but my quote above is in my capacity as a professional statistician.”
None others received.