As a new Cochrane review is published by Professor Jon Deeks and colleagues on antibody tests for identification of current and past infection with SARS‐CoV‐2, a fellow University of Birmingham expert, David Wraith, Professor of Immunology and Director of the Institute of Immunology and Immunotherapy, shares his view:
"In a detailed and thought provoking Cochrane review, Professor Jon Deeks and colleagues assess the state of play of antibody tests for CoV-2 reported in the literature thus far. The data accumulated up to now does not tell a good story. Many different types of assay are under investigation ranging from ELISA to the pregnancy test-type home testing devices, so called Lateral Flow. We have heard much about these different approaches with the UK government heralding each on in turn as a ‘game changer’. As Deeks and colleagues explain, none of the tests reported so far come up to scratch.
"They assessed 54 relevant studies and from this concluded that:
- Using these assays, antibody levels in the first week after infection are too low to allow a reliable diagnosis
- At later time points antibody levels rise to become reliably detectable after about 3 weeks
"Unfortunately, many of these studies are criticised for bias, not including sufficient numbers of control samples, for lack of blinding or analysing a sufficiently broad population of patients. Of course, there has been a rush to publish and up to now no-one has assessed the longevity of the antibody response. As it stands, these assays will give too many false positive and negative results to help with disease control.
"It is unlikely that antibody testing will replace PCR detection of the virus and hence rapid diagnosis of infection. For this to work you would need to see antibodies within days of infection and this is not how the immune system works. However, antibodies hang around long after the virus has disappeared. Antibody testing is, therefore, the sure-fire way to measure what proportion of the population has been infected previously.
"Is there hope for antibody testing? Some of the commercially available tests are searching for antibodies against the nucleocapsid protein, a protein normally found inside the virus. The antibodies we need to protect us are antibodies capable of blocking entry of the virus and here the critical protein is the Spike protein. We need to use the right part of the virus to measure the right immune response. Even then, the right type of immune response may not be found by looking in blood; since, as with other respiratory viruses, the important antibodies are those found in the mucosa lining the nose and lungs, IgA antibodies. Serum has IgA but it is a different form to that found in saliva.
"Most importantly, very few antibody studies actually measure the ability of the detected antibodies to block the virus. We need to know what type and what amount of antibody is required to block or neutralise the virus. Furthermore, we need an antibody test that is sensitive enough to detect antibodies in people who have recovered from a mild infection or who have suffered no symptoms at all, the asymptomatic population. Deeks is highly critical of the studies that only look at patients in the later stages of disease; of course they will have antibodies but what about asymptomatic individuals. We then need to know about the ability of these antibodies to neutralise the virus and how long this immune protection lasts for. Armed with this information we will be able to faithfully measure the history of infection in the population and judge what we need to do to protect people, whether this be through vaccination or isolation.
"Are we there yet? Definitely not: but it is early days and I, for one, am convinced that increasingly sensitive and meaningful assays will soon be available and that these will be specific and sensitive enough to satisfy the microscopic scrutiny of Deeks and his team of biomarker experts."