Expert Insight: The value of SARS-CoV-2 serology testing and the role of neutralization

Watch this on-demand accredited webinar to learn about the role serology plays in the clinician toolbox for managing COVID-19

18 Jan 2021

Dr. Sarah Jenks, Consultant Biochemist at NHS Lothian

SARS-CoV-2, the causative agent of COVID-19, has resulted in a global pandemic. Serology assays can be used for discerning seroprevalence, screening volunteers for vaccine trials and convalescent plasma donations, as well as predicting infection or vaccine-induced immunity.

Several commercially available SARS-CoV-2 immunoassays have been evaluated for their sensitivity and further studies have evaluated the role of the antigen target in its ability to assess protection against reinfection.

In this on-demand webinar, Dr. Sara Jenks, Consultant Biochemist at NHS Lothian, Elizabeth Furrie, Clinical Scientist and honorary lecturer at NHS Tayside, and Frauke Muecksch, Postdoctoral Associate at The Rockefeller University, explain why public health strategies going forward will be based on the ability to answer a) how circulating antibody levels that are specific for each viral antigen change with time following natural infection and b) which serological assays best predict protective immunity. 
Attendees are entitled to P.A.C.E. credits from the ASCLS and/or ACCENT credits from the AACC.

Read on for the highlights of the live Q&A session or register to watch the webinar at any time that suits you.

Q: Could you clarify that by neutralizing antibodies, do you mean IgM, IgG, or both?

FM: This would be all antibody classes. The tests we are using to figure out the neutralizing activity, that's not to distinguish between the antibodies.  For example, IgA or IgM, are in the sample — both of these would be measured.

Q: The vaccines that are currently being developed will have an efficiency of 60%. What does this mean and how is the efficiency being calculated?

SJ: I'm not best placed to comment on how the efficiency of vaccines is being worked out. I know there's been a lot of discussions in papers, certainly within the UK, around how they are defining vaccine efficacy and that it perhaps is more of a reduction in symptoms rather than a prevention of people actually getting infected. However, it just raises the question as to how these antibody tests may have a role in trying to work out who's responded and who does and does not need vaccinating, especially if the vaccines that come out of this sort of first wave of vaccine development turn out to be sub-optimal to some extent. As to how these tests fit into that kind of process, I think that is very much to be defined and it may be that these tests do turn out to have a role in that area.

Q: What exactly is the role of serology in the diagnosis of SARS-CoV-2 infection, and if you were to choose one assay, which one would you choose and why?

SJ: In terms of using the test around a key diagnosis, I think all of the available antibody tests probably do that fairly well in that most are very sensitive, picking up antibodies early on, around about the time of acute diagnosis. I think you could probably use any of the tests for that. I think where they differ in performance is as the time from infection increases and we start to see very discrepant results as we've shown with the cohort people we've been following up.

Q:  What is the structure of the neutralizing antibody?

FM: Most of the neutralizing antibodies seem to bind the receptor-binding domain of the spike region, which makes sense because this is the region that IgGs will still attach to its receptor on the cells. There are some clusters that we find recurring, the VH3 53 and 66 clusters of RBD neutralizing antibodies. A difference that we can see to the human antibody repertoire is that the SARS-2 antibodies seem to have fewer mutations.

Q: What value do you think an IgM-only assay might offer, given the frequent early seroconversion to IgG and the existing data indicating that IgM is less sensitive than total IgG in patients?

EF: Kinetics such as IgM and IgG come up almost at the same time. However, we do have a subset of patients where we persistently get negative swabs on them for PCR but we are convinced from the symptoms that they may well have SARS-CoV-2 infection. The idea is that the IgM might be able to distinguish early infection quicker than the IgG. The evidence is not there yet but you have to be aware that the MRCs that have been available so far are not terribly specific or sensitive. As MRCs evolve, we might find a better use for them, but that really is where we're thinking they might be useful in early infection before IgGs come up when we can't get positive swab results.

Q: Have you noticed any differences between the disease profiles between asymptomatic and those showing symptoms of COVID-19?

FM: In terms of neutralization, we see differences. I'm talking about other cohorts here, where people who had stronger symptoms actually developed higher neutralizing crisis. This study was done on patients who all had mild symptoms and the correlations were not that clear in this case.

Watch this on-demand webinar for more information on the role serology plays in the clinician toolbox for managing COVID-19>>