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The UK government has announced a virus infection and antibody test study in some households in England.
Sir Jeremy Farrar, Director of Wellcome, said:
“We need much better information about how many people are infected and how many people have had Covid-19 before we can be in a position to start looking at lifting restrictions in the UK. That’s why today’s announcement is so important as this testing of households across the country for the next year will help us build this picture. The samples from this programme will be tested at a central lab facility to ensure that the results are accurate.
“The results of this testing will help us track the spread of the virus within families and communities across the country and provide a true indication of how many of us have been infected in the past.”
Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:
“Excellent news that seroprevalence surveillance (have I had it?) is being embedded in a swab test incidence study (have I got it?). This joint study begins with a pilot phase. The pilot seems to focus on 20,000 to 25,000 individuals who not only participated in the past in in a representatively-sampled survey (that is: prior consenters) but also gave permission to be re-contacted (dual consenters). First consent-rate in randomly-sampled surveys in the 21st century have been around 70% with further reduction when dual consent has to be achieved.
“Surveys which begin life as randomly selected do not remain so unless consent-rates are high, ideally at least 80%.
“The pilot phase – because it approaches the previously willing – is likely to achieve participation by at least 80% of those approached in this way. However, as the COVID-incidence/immunity survey expands, I hope that it will broaden its reach beyond those who are known to have participated in previous surveys.
“I am confident that the UK public is so deeply interested in, and committed to, knowing the results about the coronavirus pandemic that high participation rates are widely achievable – precisely on account of the public’s need-to-know. For just this reason, we achieved over 80% participation rates by prisoners in our no-names HIV salivary surveillance studies (with linked self-completion questionnaire): because prisoners wanted to know the results for their prison and because we delivered the prison’s results back, always within 6 weeks.
“Two other points to consider are, first, whether the household-based design allows information about within-household transmission of infection could be gleaned? Second, respondents can grow weary of repeat testing but this risk can be reduced by randomizing each respondent to provide follow-up samples on (say) two only out of four possible repeat-sample times.”
Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, said:
“The screening of a significant cross-section of the population with the swab test (to determine if you have the infection) and the much-anticipated antibody test (to determine if you have had the infection) is most welcome. If the study is undertaken on a representative human population and the antibody test is reliable the data will be invaluable to ascertain the proportion of the population that have had the infection and are therefore likely to be immune to re-infection for a significant period of time. The tests may also be useful for transmission tracking the virus that will facilitate containment strategies and to determine if re-infection is occurring.
“The initial study of 20,000 households will be sufficient to provide statistically significant information, and it is a prudent to continue the study in real time on a larger proportion of the population. These tests and the process of capturing this important data will be a useful exercise in its own right, even if the antibody tests are not 100% sensitive and 100% specific.”
Prof Alison Sinclair, Professor of Molecular Virology, University of Sussex, said:
“It is great to see the announcement of this study because it will provide an answer to both of the key questions ‘how many people have the virus now’ and ‘how many have had it recently’. The approach of taking swabs weekly, then monthly will be important to give an estimate of the proportion of people in the country who ‘have the virus now’ and could pass it to others. This will feed into considerations being made for all of us about the benefits and risks of relaxing lock-down and social distancing measures.
“Antibodies in our blood can be detected from 2-3 weeks after infection with a virus. The blood tests to measure the antibody response will give an estimate of how many people have ‘had the virus recently’. Some may be missed because they were infected very recently, but as a snap-shot across the country the data will be a valuable estimate.
“Scientists who are modelling the epidemic and trying to predict the impact of any changes to lock down and social distancing need good estimates of how many people have been infected in the country to undertake accurate modelling. Although the numbers are relatively small, this study will give them important information to work on right now.”
Prof Keith Neal, Emeritus Professor in the Epidemiology of Infectious Diseases, University of Nottingham, said:
“This work is a really good first start in determining current and future spread of COVID-19. Testing for the virus will not identify those who have already had the virus and resistant to re-infection. The sooner it is increased to full scale (from 20,000 to 300,000) the better so we get the high quality information needed.
“Only including 1000 households in the antibody blood test section is probably too small as this is only 100 per region and we know there are regional variations in the disease. A figure of at least 10,000 tests per region is probably required to get an accurate estimate of the spread that has already occurred. Blood samples in this order are readily obtainable.
“We need to know how widespread the infection has already spread to inform the next parts of the control strategy, although it only forms part of what is needed for ongoing control.”
Prof Lawrence Young, Professor of Molecular Oncology, Warwick Medical School, said:
“We still don’t know the true extent of infection with the new coronavirus in the general population. Unlike some other countries, we haven’t performed community testing, contact tracing and targeted isolation. Without this information we don’t know how many people are susceptible to infection, particularly once the lockdown is eased. Studies from around the world have shown that many infected people have very mild symptoms or don’t even know that are infected. This new study aims to identify how many people in the general population from different parts of the country are infected with the coronavirus or have been infected in the past and now have some level of protective immunity. This information is vital in informing the government on how best to ease the lockdown and will help to us better understand how the virus is spread. It will also help us to decide how best to use a vaccine or other interventions – when they become available.”
Dr Rob Shorten, Chair, Microbiology Professional Committee, Association for Clinical Biochemistry and Laboratory Medicine, said:
Is this the ‘have you got it’ or ‘have you had it’ test, or both?
“The swab test detects the genetic material of the virus. This will tell us if an individual is currently infected. It is hoped that antibody tests will detect if a patient has had the infection.
Is this a good thing to do?
“This is a new virus so a well performed study looking at transmission and immune responses in household settings will be of use.
Will knowing more about how widespread the virus (or antibodies to it) is in the population help?
“If the antibody tests perform as hoped, then in the short to medium term these can be used to understand the proportion of individuals infected. This may have implications for future actions with regard to public health policy. The ability of these tests to detect immunity in individual patients is less clear.
Is this a big enough sample?
“Without seeing the full study protocol, we are unable to comment on this.
If we don’t yet have a good enough antibody test for widespread use, how can these people be tested for the antibodies?
“If the study is part of an evaluation of an antibody test it may help us to understand their strengths and limitations.”
Can we have a less-than-perfect antibody test for general surveillance but we still need a better one to be able to definitively know who has had the virus?
“No test is 100% perfect and understanding their limitations is crucial. The results of laboratory tests lead to actions; for the individual, the household, and for the general population. If we use a poorly performing antibody test, then the resultant actions will also be poor.”
Prof Noel McCarthy, Professor of Evidence in Communicable Disease Epidemiology and Control, Warwick Medical School, said:
Is this the ‘have you got it’ or ‘have you had it’ test, or both?
“Both. ‘Have you got it’ tests from all on a rolling basis and ‘have you had it’ at the beginning and end from some of the participants.
Is this a good thing to do?
“The idea of monitoring an ongoing level of infection in the population is good. At 25,000 planned initially this will only be able to detect very large changes since a very small proportion will be infected each month. When it gets to 300,000 it will be at a scale that will reflect the infection well, although then an enormous study. It will also give some idea of variation geographically at that stage.
Will knowing more about how widespread the virus (or antibodies to it) is in the population help?
“Yes. The added help from this compared to other sources of information building on more normal surveillance approaches is uncertain. If the country were undertaking genuine public health control including effective case finding and contact tracing and good quality national surveillance then this added study would be redundant.
Is this a big enough sample?
“At the projected final size the sample size will allow quite accurate estimation of the rates of infection at any time and the monitoring of the trend overall. The study will follow approximately 1/200 of the population then. This is probably roughly the same proportion of those infected who die from the infection. So that the study will give similar monitoring of the overall pattern of spread over time as would following numbers of deaths. Monthly testing means that the delay in the system will probably be similar to the delay in using deaths to know what has been going on recently. This study will have the advantage of knowing which sections of the population are being infected, such as which age groups, that is not evident from death monitoring alone. It may also allow confirmation on whether reinfection (implying the lack of immunity) occurs, certainly if this is a common phenomenon.
If we don’t yet have a good enough antibody test for widespread use, how can these people be tested for the antibodies?
“Having both swabs and antibodies will allow estimation of how accurate the antibody test is. So that eventually the study will be able to confirm the sensitivity of the test and adjust for inaccuracy in estimating the overall numbers.
Can we have a less-than-perfect antibody test for general surveillance but we still need a better one to be able to definitively know who has had the virus?
“Absolutely – especially if we know the ways in which the test is less than perfect and so can adjust for this in surveillance – but not to predict an individual person’s result.”
Other comments?
“Setting up parallel surveillance systems instead of building on existing public health surveillance is worrying. England used to have world leading public health surveillance and the absence of Public Health England involvement in this, as presented on the government website, appears extraordinary in what should be a coordinated national response.”
Prof Ian Jones, Professor of Virology, University of Reading, said:
“The newly announced tests should at last address the level of virus circulation in the community and, to a lesser extent, the level of past infections.
“The infectivity tests, the “have you got it” tests, are possible as a result of the scaled up testing facilities now operating in the Lighthouse Labs.
“The much lower number of antibody tests, the “have you had it” tests, reflect the fact that these tests are currently much less scalable, at least with an acceptable level of accuracy.
“Together they will give important data on how prevalent the infection is and has been. Where this has been done elsewhere the level of infection has been 20 to 50 times higher than the known positives and we must wait to see if this is also the case in the UK.”
Prof Gary McLean, Professor in Molecular Immunology, London Metropolitan University, said:
Is this the ‘have you got it’ or the ‘have you had it’ test, or both?
“This study will assess ‘have you got it’ by measuring levels of virus by PCR test, and ‘have you had it’ by antibody levels – we do not know if this will detect current infection with IgM levels, past infection with IgG levels or both.
Is this a good thing to do?
“Yes this study will provide a snapshot of the virus prevalence in the community. It is expected to increase the sample size over a 12 month period which will provide greater coverage.
Will knowing more about how widespread the virus (or antibodies to it) is in the population help?
“Yes it will give a good idea how much the virus has spread within the UK. Currently we really only know if a subset of the population has been infected based on symptoms. We still do not know levels of infection that result in asymptomatic infection and this study could shed light on that. In addition it will provide information on virus spread within households.
Is this a big enough sample?
“The first phase is a relatively small sample but the study is to be expanded over time – it should be large enough if phase 2 goes ahead.
If we don’t yet have a good enough antibody test for widespread use, how can these people be tested for the antibodies?
“There is a very reliable laboratory ELISA test for antibodies. The rapid antibody test for home use is not reliable. Presumably this study will use the highly sensitive and reliable ELISA.
Can we have a less-than-perfect antibody test for general surveillance but we still need a better one to be able to definitively know who has had the virus?
“The antibody tests will improve over time with continued development. It seems that there is a very good and reliable antibody test currently available that would be suitable for phase 1 of this study.”
Prof Babak Javid, Principal Investigator, Tsinghua University School of Medicine, Beijing, and Consultant in infectious diseases at Cambridge University Hospitals, said:
“This is an important initiative from the British government. The current Covid testing strategy in the UK, mostly confined to patients sick enough to be admitted to hospital, as well as front-line staff, significantly under-estimates the true extent of the disease in the country. Patients with symptoms, but not ill enough to come into hospital have not been tested. And estimates from similar screening projects in Iceland, as well as some communities in the United States and elsewhere, suggests that up to half, or even more patients infected by SARS-CoV2 may show no symptoms at all.
“Without knowing the true extent of infection in the community, ideally both past and present, it is impossible to make accurate projections about ‘peaks’, ‘herd immunity’ and how long distancing measures should last. The current initiative will use both the swab/PCR test that only captures current infections, and also hopes to incorporate a serological (antibody) test when one that is sufficiently accurate is available. The latter point is important: recent antibody surveys in the US, for example in Northern California conducted by Stanford University have generated a huge amount of discourse and controversy as scientists debate the true accuracy of the results, since they implied undercounting of the true scale of infection, perhaps by 50-fold.
“The proposed government strategy has a number of strengths: households that enroll will be tested multiple times over the course of the year, initially weekly, then monthly, and regardless of whether they display any symptoms of Covid or not. This will overcome potential biases in testing only those with symptoms, and, since multiple tests will be performed, will also, to an extent, overcome limitations of the test itself, which we know sometimes generates a ‘false negative’ result. However, in the absence of a reliable antibody test, it won’t capture past infections in the surveyed households. With some estimates of the cumulative prevalence of infection in London being 10% or more of the population, it would risk undercounting the extent of how far Covid has already spread throughout the country. Furthermore, as and when lockdown and other distancing measures are eased, the survey will act as a ‘canary in the coalmine’, alerting the government about potential spikes in the numbers of new cases, before numbers go up significantly enough to put a strain on healthcare resources – assuming tests are performed and analysed quickly, and that participant households do not cease participating (the swab test is not a particularly pleasant experience and repeated tests may take their toll).
“As with any other strategy aimed at Covid-19: the success of the initiative will ultimately lie in the execution. But for now, this is potentially an important element in the national response, now that we have flattened the curve of new cases.”
All our previous output on this subject can be seen at this weblink:
www.sciencemediacentre.org/tag/covid-19
Declared interests
Sir Jeremy Farrar: “Sir Jeremy Farrar is a member of the Government’s Scientific Advisory Group for Emergencies (Sage) and chaired the group who developed this testing programme.”
None others received.