Antibody tests for COVID-19

• There is insufficient scientific evidence to know whether the presence of SARS-CoV-2 antibodies confers protection from subsequent infections, and if so at what level.
• Antibodies are only one part of the immune response to infection.
• Tests that detect SARS-CoV-2 antibodies are available. They can determine whether someone has had COVID-19. Tests can reveal those who are unaware that they had COVID-19 because they had mild or no symptoms.
• Test samples must be analysed in a laboratory – no home tests are authorised for use in the UK.
• The Government provides antibody tests for NHS and social care staff, hospital patients and care home residents.
• Commercial test kits are available for private use. These are of varying quality and results must be interpreted with caution.
• A positive test does not necessarily mean that someone will be protected from subsequent infections.
• There are concerns that access to private tests of variable quality will discourage the public from practising effective public health measures.
• Antibody tests are an important tool to understand the spread of the virus and how many people in a population have been infected. They are being used in infection surveillance surveys in the UK and elsewhere.
• This is part of our rapid response content on COVID-19.  The article will be updated as the research progresses. You can view all our reporting on this topic under COVID-19.

Antibody tests can detect if an individual has been infected by a specific infectious disease and produced antibodies against the pathogen (a virus or bacterium) that causes it. SARS-CoV-2 is a new virus and, while research to understand the body’s immune response is advancing, there are several areas of uncertainty. This, and the varied quality of antibody tests, means that there are significant limitations in how test results should be interpreted. Such tests are key elements of research, medicine and public health monitoring. There is increasing interest in how they might be part of policies that seek to use them as a tool with which to manage enforcement or lifting of containment measures at individual level. This article explains how antibody tests work and which ones are available, what they can tell us about how many people have had COVID-19, and the strengths and weaknesses of using them in different contexts. It also highlights the latest research examining how many people have SARS-CoV-2 antibodies. More background information is provided in this article, Immunity to COVID-19.

Antibody tests

Antibody (also called serology) tests can determine whether a person has SARS-CoV-2 antibodies that have been produced as part of an immune response to previous infection. They are less useful for diagnosing a current infection – this is done using a polymerase chain reaction (PCR) test, which amplifies the genetic material from samples collected from the nose and throat in the first few days of an infection. This infographic from the American Society for Microbiology describes the differences in COVID-19 test types.

Current antibody tests in the UK use a blood sample, which must be processed in a laboratory. It is up to national regulators and other bodies to determine which tests meet the standards they specify for use in healthcare or other settings. The European Centre for Disease Prevention and Control has set out guidance on tests. The Medicines and Healthcare products Regulatory Agency has published guidance on the characteristics that tests bought by the UK Government should have. Two key criteria specified by the MHRA are that tests pass a threshold of 98% for both clinical sensitivity and specificity, explained below.

Test accuracy

An antibody test must be specific and sensitive in order to be accurate. If not, then it will lead to people being incorrectly categorised as having had the infection when they haven’t (false positive) or not having had the infection when they have (false negative). A test must specifically detect SARS-CoV-2 antibodies and not react to other coronaviruses. If it did this then it would also lead to false positive results.

• Specificity of a test refers to if it can correctly produce a negative result for people who do not have antibodies. A test with 100% specificity will rule out everyone who does not have the antibodies. No false positive results are produced, and all positive test results are correct. A test with 95% specificity will return a correct negative result for 95% of people who do not have antibodies but will produce false positives for 5% of people.

• Sensitivity of a test is a measure of how often it generates a positive result for people who have antibodies. A 100% sensitive test will detect everyone with antibodies and not generate false negative results. A test with 95% sensitivity will produce a positive result for 95% of people with antibodies, but 5% of people will have a negative result (who should have tested positive).

In addition to sensitivity and specificity, it is important to consider the circumstances in which a test is being used. One of the most important considerations is how common an infection is in a population (its prevalence). This is discussed later.

Antibody tests on the market

National governments, research institutions and commercial organisations have developed antibody tests. Tests can be designed to meet different specifications according to the purpose for which they are to be used. For example, the US Centers for Disease Control and Prevention has developed its own test to use in national research and surveillance programs.

New SARS-CoV-2 antibody tests are checked by medical regulatory agencies to make sure that they meet the standards required by healthcare settings. Some of these tests, and others, are also commercially available for private purchase, but they must carry a CE mark. The US Food and Drug Administration has published data on the performance of numerous tests it has authorised for use. Public Health England (PHE) has evaluated some commercial tests to examine the claims of accuracy cited by the manufacturers:

• Abbott’s antibody test, which requires a blood sample for laboratory analysis. The company claims specificity of 99.6% and sensitivity of 100% for tests 14 days after symptoms began. Tests by Public Health England reported specificity of 100% and sensitivity of 92.7%.
• Ortho Clinical Diagnostics antibody test requires a blood sample for laboratory analysis. The company claims specificity of 100.0% and sensitivity of 90.0% for tests 15 days after symptoms began. Tests by Public Health England reported specificity of 99.7% and sensitivity of 77.4%.
• Roche’s antibody test requires a blood sample for analysis in a laboratory. The company claims specificity of 99.8% and sensitivity of 100% for tests 14 days after a patient tests positive for an infection with an antigen test. Tests by Public Health England reported specificity of 100% and sensitivity of 83.9%.

It is important to note that tests with less than 100% specificity and sensitivity will generate false positive and false negative results. The specificity of the above tests is very high, so the rate of false positives is low, and they will identify people who have previously had the virus. However, the specificity of tests becomes even more important where fewer people in the population have antibodies. This is because it becomes more likely that a test with specificity of less than 100% will result in a higher proportion of false positive tests. As the prevalence of antibody in the population increases, real positive results outweigh false positives and the data become more reliable.

There is scope for inaccuracies due to the sensitivity of these tests, leading to false negative results. For example, if a group of people who had had COVID-19 took the Roche test, it would generate a false negative result for about 16% of them, according to the PHE data. Test accuracy will also depend on when the test is taken. These tests are less reliable if taken in the first 2 weeks of an infection. This is because it takes time to build up levels of antibodies after becoming infected.

Laboratory and home testing

Currently, SARS-CoV-2 antibody tests approved by regulatory agencies require laboratory analysis of samples, with the sample taken in a healthcare setting, at a testing centre or at home. Some tests are always done by a healthcare professional because of the way a sample needs to be collected (such as taking blood from a vein) and analysed or because the result needs to be interpreted by a professional. Home tests involve taking and testing the sample at home, with an immediate result, like a pregnancy test. There are no CE marked home tests for detecting SARS-CoV-2 antibodies, but there are home sampling kits.

For SARS-CoV-2 tests, a blood sample can be taken from a vein or by pricking a finger depending on the test type, but the sample must be analysed in a laboratory. It is important that the manufacturers’ instructions are followed, otherwise the results can be unreliable. Some UK retailers are selling home antibody tests that use a blood sample using the finger-prick technique which are then analysed in a laboratory. The Medicines and Healthcare products Regulatory Agency (MHRA) recently asked antibody test providers like these to suspend their services while they test if the finger-prick blood sample is an accurate method to use.

Sampling kits that can be carried out at home are convenient and could be a useful research tool for widespread testing. A serious concern is public understanding of a test’s limitations, so that an individual has some context in interpreting their result if they choose to test privately.

Interpretation of antibody test results

The key message is that using and interpreting the results of antibody testing is not straightforward and requires informed analysis. The main concerns:

• Someone with a false negative result might think they are at risk of infection when in fact they might have some level of protective immunity, meaning that the risk they pose others is less.
• Someone with a false positive result may assume they have immunity when they do not and then may take unnecessary risks.
• Someone with a valid positive result will have antibodies to SARS-CoV-2. However, this may not necessarily mean that they are immune to subsequent infection and not at risk of being reinfected. An antibody test by itself is not necessarily a sign of protection. There is also a lack of evidence on how long, in terms of durability of antibodies, a test result could be regarded as valid.

These concerns are particularly relevant where tests are used as the basis on which to change behaviour – for example attending workplaces or mixing with people who are clinically vulnerable.

The key value of these tests at present is their use in large scale surveillance programs and for vaccine development.

UK Government antibody testing programme

The Government has a national five pillar COVID-19 testing programme, which includes antibody testing. A policy paper published on 4 April states that the Government sees antibody tests as a route to enabling people who think that they have had the disease to get back to work, as well as a tool with which to work out what proportion of the population has been infected. The Office for National Statistics is conducting population antibody testing as part of its national COVID-19 infection survey, discussed later.

International serosurveillance data

The World Health Organization has published guidelines on global surveillance for COVID-19.

Serosurveillance, or seroprevalence studies, use antibody tests and can be used to:

• Estimate the proportion of people in a population who have been infected since the pandemic began.
• Track the geographic spread of infection.
• Track the numbers of infections over time.
• Identify risk factors associated with infection.
• See how long antibodies remain in the blood following infection.
• Identify people who have had the infection but who had very minor or no symptoms that might not have been counted as COVID-19 cases.

Many countries have such projects underway, at the national population level, or within certain sub-groups such as healthcare workers, contacts of those infected, or individual households. While these studies are a useful way to determine how many people have antibodies, they are not designed to examine whether people will be immune to subsequent infection. It is possible to use antibody tests with lower specificity and sensitivity in surveillance studies than those used on individual patients. This is because statistical techniques can be applied to take account of this. Some data from small studies that have already started are reported below; in each case the level of antibody prevalence is significantly below the threshold needed to achieve population-level immunity, estimated to be between 60–80%. Other larger scale national seroprevalence projects are highlighted below.

Denmark

A preprint research study looked at samples from blood donors between 6–17 April. Of 9,496 donors aged between 17–69 years, 1.7% had SARS-CoV-2 antibodies. There were some differences between geographic areas.

France

A preprint research study of samples from local blood banks in an area of Northern France with a cluster of COVID-19 cases found that 3.0% of donors had SARS-CoV-2 antibodies.

Germany

A national study of the prevalence of antibodies in the population will be led by the Helmholtz Centre for Infection Research; the Multi-local and serial cross-sectional prevalence study on antibodies against SARS-CoV-2 in Germany (MuSPAD).

Italy

The Ministry of Health launched a national seroprevalence study on 25 May, in collaboration with the Red Cross. A weighted population sample of 150,000 people from 2,000 municipalities will be included. One of the aims of the study is to estimate the number of people who have had COVID-19 but have not had symptoms. It will also inform policy-making on future containment measures.

Netherlands

A preprint research study looked at blood samples collected from adult blood and plasma donors between 1–15 April. It reported that 2.7% had SARS-CoV-2 antibodies. There were geographic differences in the data, with seroprevalence up to 9.5% in areas in which more infections occurred.

Spain

The first wave of a national seroprevalence study reported that 5% of a weighted sample of 60,897 people had antibodies.

Sweden

Sweden’s public health authority reported antibody prevalence in an 8-week study of nine regions that was published on 20 May. There were regional differences in the proportion of people with SARS-CoV-2 antibodies: Stockholm had 7.3%, Skåne 4.2% (a county in southern Sweden) and Västra Götaland 3.7% (a county in south west Sweden that has had a lot of cases). Those aged 20–64 years were more likely to have antibodies: 6.7% compared with 2.7% of those aged 65 years and over.

Switzerland

A study evaluated IgG antibody levels in a population in Geneva. They tested 2,766 people aged over 5 years in 1,339 households, over 12 weeks. They found that the percentage of people with antibodies was 4.8% in week one, 8.5% in week two, 10.9% in week three, 6.6% in week four and 6.6% in week five. Children aged 5–9 years and adults aged over 65 years were less likely to have antibodies than those aged 10–64 years.

UK: England

The Office for National Statistics is releasing data from a pilot COVID-19 Infection survey that seeks to estimate how many people in England have had the infection. The first tranches of data show that the estimated percentage of the community population (not including those in hospitals or care homes) that were currently infected at that time, fell from 0.4% (between 26 April–2 May) to 0.10% (17–30 May). Data published on 12 June reported that at any time between 25 May–7 June the estimate was 0.06%. This is equivalent to 33,000 people in England. The emerging trend is that the number of people testing positive is decreasing.

There is a range of uncertainty associated with these figures, which more data in subsequent weeks will address as the survey expands. The survey uses PCR tests (which detect presence of the viral genetic material) on about 20,000 people to see which of them had an infection at that one time point. The survey also used antibody tests on blood samples from 885 participants and found that around 6.78% tested positive since the study started on 26 April. This represents about 1 in 15 people. It is important to note that for these data it has not yet been possible to adjust them to make them truly representative of the whole population. This is because of the small number of people in the sample who have tested positive, but this will be possible as the number of samples increases.

UK: Scotland

A preprint research study of blood donors in Scotland tested 1,000 samples for SARS-CoV-2 antibodies, specifically neutralising antibodies. Of the 500 samples tested on 17 March, all were negative. A further 500 samples collected between 21–23 March were tested, of which five tested positive. The researchers draw the cautious conclusion that this increase ties in with the increasing frequency of reported infections in Scotland in that period, and highlight the need for ongoing studies to track infections and seroprevalence in larger groups of people that are representative of the population as a whole.

Implications for immunisation programmes

Understanding the duration of immunity is a key consideration for the development of immunisation programmes. If immunity wanes quickly, this could indicate that a COVID-19 vaccine would be needed at regular intervals to boost protection. This is partly why the influenza immunisation programme is delivered annually in the UK, with at-risk groups immunised every year. There are also uncertainties about how the virus may evolve in response to the human immune response.

Immunity certificates

An approach suggested by some governments is to allow people to return to work, to travel or undertake other activities based on proof of immune status using the presence of antibodies as a proxy, through issuing immunity passports, permits or certificates. This raises ethical questions as to how an individual’s antibody status might be used to limit their right to travel, socialise and access employment, alongside wider impacts regarding privacy and possible discriminatory practices.

The World Health Organization has issued guidance on this, outlining that there is insufficient evidence on antibody-mediated immunity to guarantee the accuracy of immunity passports. They also argue that people who have a positive antibody test may be less likely to comply with public health advice, which poses a risk for virus transmission.

The Scientific Pandemic Influenza Group on Behaviours (SPI-B) is one of the sub-groups advising the Scientific Advisory Group for Emergencies (SAGE) on COVID-19. SPI-B discussed antibody tests on 1 April. The group highlighted the uncertainties in the accuracy of tests, the potential for test results to be misunderstood and misused, and how the latter concerns can be mitigated. They also highlighted that those who test positive may still be able to transmit the virus, for example by touching contaminated surfaces. Therefore those people who have a positive antibody result must continue to practise good hand hygiene. This is because people testing positive are at low but not zero risk of transmission, and that people who test negative are still at risk of infection and transmission.

Other issues are likely to arise from the use of antibody tests include inequitable access; how they might be used to discriminate employees in workplaces; whether they may legitimise unsafe working practices; the risk that poor quality tests may become available; and that a market in selling poor quality, fraudulent and fake certificates could arise. SPI-B made a series of recommendations to Government to maximise the benefits of antibody testing while minimising potential harms.

Research priorities and current UK projects

The British Society for Immunology and the Academy of Medical Sciences have published a research review, outlining current knowledge and identified thirteen key research priorities that are most likely to lead to meaningful results with direct relevance for public health in 12–18 months. These include understanding which antibody properties confer protection, how many people in the population have antibodies, the quality of current tests, and the duration of natural and vaccine-mediated immunity.

The National Institute for Health Research (NIHR) is funding research designated as national priorities by the Chief Medical Officer. Professor Richard Tedder, Imperial College London has received NIHR funding to develop a non-invasive test to detect SARS-CoV-2 IgG and IgM antibodies in saliva samples. This type of test will enable easy sampling of large numbers of people. The aim is to have a test within 6 months.

UK Research and Innovation (UKRI) has allocated £24.6m for COVID-19 research. Professor Matthew Snape, University of Oxford was awarded funding to research immunity in children. The study will test for the presence of SARS-CoV-2 antibodies in a sample of children aged 0–19 years. The results will improve understanding about how many children and teenagers have been infected and what proportion of them had symptoms.

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