With the advent of vaccines against the SARS-CoV-2 virus, the COVID-19 pandemic entered a new phase. In a recent webinar hosted by Roche Diagnostics Asia Pacific, two leading laboratory experts discussed how testing strategies may evolve in the post-vaccine era, including the changing role of antibody testing. Here are some of the key takeaways.

Combination testing gives better results

In the early days of the pandemic, laboratorians scrambled to develop or implement any assay for SARS-CoV-2 testing. Now, there are many tests available, ranging from rapid antigen tests to molecular assays and serological tests.

Since laboratories now have access to so many testing options, they should consider implementing combination testing for the best results, according to Prof Aw Tar Choon, Senior Consultant and Director of Chemical Pathology at Changi General Hospital in Singapore. For example, using antibody tests with molecular assays gives a more detailed view of a patient’s health. Two negative results mean the person was not exposed to the virus, while two positive results mean there’s an active infection that has been underway long enough for the immune system to mount a response. A positive PCR test and negative antibody test indicate the patient is in the earliest stages of infection.

“Two tests will always give us much clearer and better information,” Prof Aw said, noting that the combination boosts positive predictive value for PCR tests.

Performing two tests also helps to overcome timing challenges associated with current assays. PCR tests performed too late may give negative results even for people who have been infected, while serological assays performed too early may not pick up the nascent stages of an immune response. For some people, antibodies can be detected within 48 hours of exposure to the virus; for others, it takes at least a week to get measurable levels of antibodies. “For antibody testing, the timing of sample acquisition is vital,” Prof Aw said.

Rapid antigen tests are known to have lower accuracy and, in general, work best in the early stages of infection. They are primarily recommended for self-testing to detect infected cases more quickly, or situations where molecular tests are not feasible due to availability, affordability, workflow constraints, or other factors. However, rapid antigen tests can be paired with antibody tests for improved results as well.

Longitudinal studies are underway

As researchers seek to understand the immune response to both natural infection and to vaccination, longitudinal studies will be very important. One of the main questions that researchers want to answer is: at what antibody level does someone have protection?

One of those researchers is Prof Stefan Holdenrieder, Director of the Institute of Laboratory Medicine at the German Heart Centre of the Technical University in Munich, Germany. He is currently performing longitudinal studies designed to monitor immune response using different markers in many people over time. His results, together with other ongoing studies led by Prof Aw and others, will help inform our understanding of how varying antibody titers correspond to real-world protection against the virus.

In these studies, scientists are looking at IgG and IgM levels associated with antibodies to the spike protein and nucleocapsid. Antibodies to the spike protein, a common target of COVID-19 vaccines, can be used to characterise response to vaccination. Antibodies to the nucleocapsid, which has not been targeted by vaccines, indicate response to a natural infection. Longitudinal studies will check for both to profile immune response among vaccinated individuals and to determine whether those people develop breakthrough infections after vaccination.

So far, longitudinal studies have demonstrated strong and ongoing protection from the most widely used vaccines. Antibody levels are measurable for several months among people receiving the Moderna or Pfizer/BioNTech mRNA vaccines. “There’s optimism that the vaccine will work for at least a year,” noted Prof Aw.

In Germany, Prof Holdenrieder’s team is also trying to determine whether there is a correlation between antibody levels and the presence of neutralizing antibodies. For all study participants, the team will collect blood draws at four weeks, three months, six months, and 12 months after the second dose of the vaccine. In addition to being tested with antibody assays, cellular assays, T cell stimulation assays, and more, all samples will be banked for future analysis.

Immunity testing is useful but not always recommended

Beyond longitudinal studies, immunity testing to measure antibody levels for people who have recovered from COVID-19 or been vaccinated may be important — but experts say it will likely not be universally needed.

It may also prove technically difficult. “There are a lot of challenges for the labs,” said Prof Holdenrieder, pointing to the wide range of immune responses depending on type of exposure, type of infection, duration of infection, and vaccination status. As antibody rates naturally decline over time, he noted that it may be necessary to start measuring T cells and B cells for a view of an individual’s immunity.

Prof Aw pointed out that immunity testing is not typically done for vaccines such as influenza vaccine, but checking immune responses is recommended for hepatitis B vaccine. He does not expect that labs will need to perform these tests for all people. However, certain groups — such as transplant patients with suppressed immune systems who may need a third booster shot to receive protection — would be appropriate for more vigilant testing. He added that if vaccine supply becomes badly limited again, then immunity testing may be used to determine which people are most in need of a booster shot.