It’s time to check antibodies and take the guesswork out of this pandemic

Whether you got vaccinated back in the spring, or you got COVID-19 a year ago — or both — are you protected from the virus? Should you get a booster? If so, when? If you are organizing an event that requires immunity, is confirming vaccination enough? Should you also confirm boosters for those who were vaccinated back in December 2020? Is it reasonable to include those with natural immunity who have not been vaccinated?

Thus far, there have been no good answers to any of these questions, which has caused significant confusion, frustration, risk and even animosity. Fortunately, antibody testing might be ready for primetime. Early tests only returned “positive” or “negative” and had questionable reliability, but now well-established, validated semi-quantitative tests can measure not just whether you have protective antibodies, but the level of those antibodies.

It was through semi-quantitative testing of thousands of patients that our research group at Johns Hopkins discovered that transplant patients and other immunocompromised individuals have poor immune responses to the vaccines and need additional doses. Semi-quantitative tests are now widely available and often don’t even require a doctor’s order.

We are also learning that antibody levels correlate with plasma neutralizing capability (your immune system’s ability to kill the virus in a test tube) and even with clinical protection (your ability to fight off a breakthrough infection). In a recent sub-study of the landmark Moderna trial, every 10-fold increase in antibodies meant an additional 34 percent lower risk of a clinical breakthrough infection. This means that across the “positive” range for antibody testing, some people have one-third the risk of a breakthrough infection compared to others.

Of course, antibodies are not the only component of the immune system. There are T-cells, memory B-cells and complex interactions between complex systems. However, antibodies are the mainstay of the immediate-early immune response, providing truly sterilizing immunity, so antibody levels determine how quickly you can react to the virus.

Antibody levels are critically important for two reasons: First, the faster you can react to the virus, the less time the virus has to replicate before your immune system kills it, so the less severe your infection will be. Second, and maybe even more important in the context of public health, the faster you can react to the virus, the less time you will be shedding virus asymptomatically and unknowingly putting others at risk. Imagine how many people you would unintentionally expose in a week of shedding the virus without symptoms. Keeping everyone’s antibody levels up could prevent future waves of this awful pandemic.

Boosters have started rolling out for individuals who were vaccinated early on, under the presumption that durability wanes with time. In other words, at the general population level, it seems that after six to nine months, antibody levels are much lower than they were after initial vaccination. We know that if antibody levels fall, protection falls, so boosters are needed. But when? At six months? At nine months? At 12 months? Is it different in older adults? Is it different in those who are immunocompromised in other ways?

Instead of just guessing, or assuming “one size fits all” (we saw what a disaster it caused when we assumed immunocompromised patients had the same response as everyone else), we can now test antibody levels and recommend boosters when levels fall below some threshold. We can even choose different thresholds for people of different risk profiles: If you have a higher risk of exposure to SARS-CoV-2 (or exposing others) because of your job, or if you have a higher risk of getting very sick with COVID-19 because of your comorbidity profile, you should get boosted at a higher antibody level. B if you have minimal exposure and are otherwise quite healthy, you could wait to reach a lower antibody level before boosting. This individualized approach would optimize protection while making the best use of available vaccine doses.

Antibody testing can also help us address the major controversy over natural immunity and “vaccine passports.” Many venues, including theaters and concerts and festivals, are starting to require proof of vaccination for entry. Unfortunately, this is quite a blunt instrument for determining how safe someone is to be around others, and it is becoming more and more unreliable as antibody levels from initial “full” vaccination are waning. Ideally, a space is safer if everyone in the space is immune: The risk of someone bringing the virus to the space is minimized, and the risk that the virus would impact the other immune folks in the space is also minimized.

So why have “immunity passports” devolved to “vaccine passports”? For a while, checking vaccination was much easier than somehow determining that someone had enough natural immunity to be safe: In the large clinical trials, nearly everyone mounted a strong antibody response to vaccination, so asking to see someone’s vaccine card was as close to a guarantee as we get these days that the person was immune. However, we are almost a year into vaccines, and antibody levels wane. Today, even vaccination does not necessarily mean strong immunity, and someone who had documented COVID-19 three months ago is likely more immune that someone who was vaccinated a year ago. The way to determine this is to check antibody levels: At a given antibody level, no matter how you got there (vaccines with or without boosters, natural infection with or without vaccines), it is safe for you to be around others.

This will take work. We have to choose the semi-quantitative antibody testing platforms that we trust. We have to choose an antibody level that is “safe enough.” And we have to figure out the logistics of how to check and confirm antibody levels. We could use a hybrid system of a vaccine dose within the last X months or an antibody level above a certain threshold within the last X months, or we can even get fancy with mathematical models of antibody waning. Whatever we do, it won’t be perfect. But it will be much better than what we’re actually doing right now, which is ignoring that vaccine immunity wanes, and ignoring that natural immunity can be just as powerful.

Dorry Segev, MD, Ph.D., is a professor of surgery at Johns Hopkins University School of Medicine and Professor of Epidemiology at Johns Hopkins Bloomberg School of Public Health. Segev has been leading an observational study of COVID-19 vaccine responses in immunosuppressed people since December 2020 and is the principal Investigator of the NIH/NIAID-funded interventional trial “COVID-19 Protection After Transplantation (CPAT).” Follow him on Twitter: @dorry_segev