The role of antibody testing for understanding immunity to COVID-19 and the response to mass vaccinations

Never before has testing for virus infection been such a hot topic. Whether it is testing individuals with COVID-19 symptoms to determine if they are infected with the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) virus ahead of isolating and contact tracing or performing large scale surveys to ascertain the overall levels of infection in the community, everybody is now familiar with the need for and value of diagnostic testing.

Terms like PCR tests (Polymerase chain reaction test) and lateral flow devices have become part of the everyday vernacular and now we also have surge testing coupled with genomic sequencing to identify the presence and spread of virus variants. All these technologies are aimed at detecting individuals during the acute phase of SARS-CoV-2 infection when the virus is replicating and able to spread to other people.

Understanding a person’s immune response to COVID-19

coronavirus cell like covid-19 or a flu virus structure with spike proteinsThe most contagious period is around the time of symptom onset or in the first week of illness with infectivity rapidly decreasing to near zero after 10-15 days depending on the severity of the disease. However, around 30% of infected individuals have no symptoms but are probably infectious, albeit at a lower level than symptomatic cases. This means that it is easy to miss the window during which an individual is most infectious and that non-infectious viral RNA fragments detected by PCR post-infection can confuse the determination of infectivity.

“Testing for the virus itself is meaningless around 2 weeks after initial infection and tells us nothing about the individual’s response to infection.” Prof. Lawrence S Young.

While the viral load peaks during the first week of infection, the antibody response to SARS-CoV-2 gradually rises and is often detectable by day 14 after the onset of symptoms. This antibody response is broad covering a range of viral antigens, but most serological assays focus on either the spike protein or nucleocapsid protein.

SARS-CoV-2 Spike proteins, neutralising antibodies and vaccines

The spike protein is the major target for virus-neutralising antibodies, and it is assumed that this response will provide a correlate of protection from infection. Thus, all current virus vaccines contain the spike protein, and all clinical trials use various approaches to measure neutralising antibody responses and correlate this with the clinical efficacy of the vaccine.

Recent studies suggest that these antibody responses may last for at least 5 to 8 months and that this is likely to provide protection from re-infection over that period. We know from other coronavirus infections that the immune response wanes over a period of the time, but we do not know the time course of this for SARS-CoV-2 infection and how this might impact susceptibility to reinfection.

What is the value of COVID-19 antibody testing?

a doctor detecting neutralising anti-spike protein antibodies via rapid antibody testing

Public health monitoring continues to be an important way to understand the spread of virus infection in the community including measuring antibodies to determine how many people have had a previous infection. Such seroprevalence data has recently been highlighted by the UK Biobank study which has shown, in a study of over 20,000 participants, that 99% of those who ‘tested positive for previous infection retained antibodies to SARS-CoV-2 for 3 months after being infected, and 88% did so for the full 6 months of the study’.

Similar studies are using antibody testing to determine the strength and longevity of the immune response in patients after symptomatic COVID-19 and to monitor the response to vaccination. At the individual level, antibody testing can be used to confirm previous COVID-19 in those who are no longer PCR positive but present with current symptoms two weeks or more after the onset of disease. Such testing is also useful in those without symptoms as a measure of previous SARS-CoV-2 infection to inform decisions about returning to work. It also raises the controversial and topical issue of immunity passports and the value of antibody testing in returning us all to a more normal existence.

The need for rapid and accurate tests

What we need are rapid and accurate tests for neutralising anti-spike protein antibodies that can be used for determining the spread of SARS-CoV-2 and its variants in the population as well as the impact of mass vaccination. Such tests would also be useful at the individual level (e.g., workplaces, airports, pharmacies, GP practices) to provide confidence of on-going protective immunity.

About the Author

This blog was authored by Professor Lawrence S. Young, an internationally recognised virologist and Pro-Dean for External Affairs at Warwick Medical School and Director of the Warwick Cancer Research Centre.

Prof. Young is also on Abingdon Health’s Medical and Scientific Advisory Board.