Guidance

Antibody testing for SARS-CoV-2: key information

Updated 4 April 2022

Context

People are increasingly accessing antibody testing, either through various different surveillance studies, private providers, or directly through government-supported services. As more people access antibody tests there is an increasing chance that people approach health care professionals for advice, particularly after vaccination.

This guidance provides healthcare professionals key information on how antibody tests should be interpreted. It is complemented by Extended information for medical professionals and researchers on using and interpreting SARS-CoV-2 antibody tests, which provides additional information on the antibody response to SARS-CoV-2 (the coronavirus that causes COVID-19) infection, including interpretation of atypical antibody responses and responses in special groups.

Antibody response against SARS-CoV-2

Most people infected with SARS-CoV-2 generate antibodies against the structural proteins of the virus. Most antibodies are made against parts of the spike (S) and nucleocapsid (N) proteins. Tests available to NHS clinicians are lab-based and measure antibodies made against these proteins: anti-S or anti-N antibodies. All SARS-CoV-2 vaccines currently licensed in the UK, USA and EU contain only the S protein or gene. Therefore:

• anti-N positive confirms previous infection
• anti-S positive confirms previous infection and/or response to vaccination

In immune naive people, antibodies are made from 4 days post infection or immunisation (exposure) and become reliably detectable within 20 days of symptom onset, but can take longer.

It is not yet known what level of antibodies are protective against infection. It is highly likely that higher antibody levels are more protective than lower antibody levels; however, the ‘correlate of antibody derived protection from infection’ – the titre of anti-S neutralising antibody to prevent viral infection (sterilising protection) – for SARS-CoV-2 is unknown. Therefore it is not possible to give individuals a binary answer as to whether they are fully protected from COVID-19, merely that they are better protected than if they had no antibodies. A person with antibodies is highly likely to be protected against severe disease.

Antibody testing capability and uses

Testing for anti-SARS-CoV-2 antibodies has several uses:

• to inform if a patient is likely to benefit from monoclonal antibody (laboratory-made antibodies that attack the virus) treatments in hospital
• to understand vaccine effectiveness, monitor the impact of variants of concern (VOCs) and estimate prevalence of infection

Immunity against SARS-CoV-2 – current understanding

Previous infection or immunisation are highly likely to provide effective protection from death and severe disease in those who are subsequently infected. This protection is highly likely to be similar across age groups.

It is almost certain that variants will continue to emerge and that the protective effect of prior exposure or vaccination will be reduced against at least some of these variants. UKHSA regularly publishes technical information on variant and vaccine surveillance, see vaccine surveillance reports (weeks 39 to 49).

T-cells (a type of immune cell) also play an important role in protecting against SARS-CoV-2 infection, but are much harder to measure than antibodies. A wholly T-cell driven response to SARS-CoV-2 is rare, and antibody testing remains the most accessible marker of immune response.

Result interpretation and SARS-CoV-2 antibody mechanics

The levels of antibody (antibody titre) produced after vaccination or infection vary. In general, more severe disease tends to lead to higher antibody titres once the patient has recovered from their first infection. Anti-S antibodies are present in the vast majority (greater than 99%) of individuals^{[footnote 1]} 28 days after a full SARS-CoV-2 vaccination schedule.

Anti-S antibodies are detectable for at least 20 months following infection in most individuals, while anti-N antibodies tend to decline faster. Waning of antibodies, even to levels below the detectable range, will likely not significantly reduce protection from severe disease due to the role of T and B cell driven immunological memory. Anti-N response after infection, in general, decays faster than anti-S.

Anti N	Anti S	Interpretative comment
Positive	Positive	Suggestive of previous SARS-CoV-2 infection (anti-N). Antibodies found after SARS-CoV-2 vaccination present, but these are also present after infection
Not assessed	Positive	Antibodies found after SARS-CoV-2 vaccination present, but these are also present after infection. Suggestive of response to SARS-CoV-2 vaccination or prior infection
Positive	Negative	Suggestive of previous SARS-CoV-2 infection (anti-N). Antibodies that we would expect to see after vaccination were not identified
Positive	Not tested	Suggestive of previous SARS-CoV-2 infection (anti-N)
Negative	Positive	Antibodies found after SARS-CoV-2 vaccination present, but these are also present after infection. Suggestive of response to SARS-CoV-2 vaccination or prior infection
Negative	Negative	No serological evidence of past exposure
Indeterminate with other target, neg or indeterminate	Indeterminate with other target, neg or indeterminate	Difficult to interpret SARS-CoV-2 IgG. Please send a repeat sample in 2 weeks

Assay types

Lab-based assays

Lab-based assays are considered ‘gold-standard’. UK Health Security Agency (UKHSA), NHS labs and certain private providers offer lab-based assays of blood samples against the anti-S or anti-N response. UKHSA regularly reviews the performance of antibody assays and you can find more information on these reviews on GOV.UK.

Point of care assays

Point of care (POC) assays are, generally, less sensitive than lab-based assays. Clinical specificity varies between assays. These tests are routinely used in surveillance studies where results can be adjusted relative to performance of the assay of choice. POC assays are not recommended for individual use but are a useful tool for surveillance and research studies.

Evidence base

Longitudinal surveys of reinfections with SARS-CoV-2 and the antibody response over time are extensive in the UK. These include general population studies such as the ONS COVID-19 Infection Survey and priority cohort surveillances such as healthcare workers (SIREN) and care home staff and residents (Vivaldi).

These studies have contributed to an emerging research picture underpinning the key observations outlined above. Read more on COVID-19 surveillance and immunity studies.

Probabilistic language

• ~0% to 8%: remote chance
• ~10% to 20%: highly unlikely
• ~25% to 35%: unlikely
• ~40% to 50%: realistic possibility
• ~55% to 75%: likely or probably
• ~80% to 90%: highly likely
• ~95% to 100%: almost certain

1. When lab-based quantitative assays are used. ↩