Do Antibodies Equal Immunity?

Health officials and people around the world have been looking toward a COVID-19 vaccine to finally bring an end to the pandemic that has infected over 70 million people worldwide, killing around 1.7 million.

But many people who have recovered from the virus and now possess COVID antibodies are wondering why health authorities are not recognizing those with antibodies as possessing COVID immunity.

Last Thursday — days after New York City began administering the vaccine developed by Pfizer and BioNTech, and one day before the FDA granted authorization to another vaccine, developed by Moderna — Hamodia spoke with Dr. Jay Varma, Senior Advisor for Public Health to New York City Mayor Bill de Blasio, to discuss why health officials are not giving “immunity passports” to people with positive COVID antibody tests.

Dr. Varma has served on the CDC’s Epidemic Intelligence Service, working on foodborne diseases; directed the CDC’s tuberculosis programs and research in Southeast Asia; directed the CDC’s International Emerging Infections Program in Beijing; served as the Deputy Commissioner for Disease Control at the New York City Department of Health and Mental Hygiene; and served as Senior Advisor at the Africa Centres for Disease Control and Prevention.

Dr. Varma has authored over 125 scientific manuscripts, six essays, and one book. A captain in the U.S. Public Health Service, Dr. Varma has been recognized as the U.S. Public Health Service Physician Researcher of the Year (2010) and Physician Leader of the Year (2017), and has received the two highest awards in the U.S. Public Health Service: the Distinguished Service Medal in 2011, and the Meritorious Service Medal in 2018.

Interview has been edited lightly for clarity.

—

Thanks so much for joining us today. I know you’re really busy with the rollout of the vaccine. How’s that going?

Good. This is a moment that everybody in public health has been waiting for anxiously. Obviously, every program takes a little while to start up, but all the hospitals are working very actively to make sure that everybody who’s eligible for the vaccine gets it quickly, and so we’re excited to see this move forward.

Health authorities are really excited about this and talking about the vaccine ending the pandemic. But there are so many people who have had the virus and have antibodies. So what I’d like to discuss is why health authorities are not recognizing antibodies from the virus, as immunity.

Immunology is a very complex issue, because there is a lot about this virus that we don’t know for sure.

Let’s go to what we do know: What we do know is that in a vaccination study — and we have the one from Pfizer and we have the one from Moderna that have been completed — you are giving people a very well-prescribed stimulation of the immune system. In this situation, it has nothing to do with the virus itself, it’s just the code or the message that tells your body to generate a response to the virus. And then we’re able to measure, in a very clear way, who was protected and who was not protected. So that is why getting your immune system protected through a vaccination is always the preferred way.

The other reason to have your vaccination, of course, is that when we study it and we prove that it’s safe, there is no risk of death from the vaccination, whereas there is a risk of death, of course, with infection. So that’s the reason why vaccination’s always important.

The question you’re asking is, should we prioritize vaccination for people who have never been infected before, or should we just tell people who’ve been previously infected, “You don’t need to be vaccinated”? There are a couple of areas related to that; let me just try to tick through them really quickly.

The first is that people’s individual responses to previous infection vary. There have been a number of different studies, and all of them show a fairly reliable conclusion that if you had a confirmed infection, you are almost certainly protected for a few months after that infection. What we don’t know is who remains protected after that period, and for how long you remain protected, and which subset of people don’t actually get any protection at all. So that remains an area of uncertainty.

The second question is, what happens if you never had a confirmed infection, but you only had a positive antibody test? And that’s another area in which there’s still a lot of uncertainty. The uncertainty is that, at least from what we know from the small studies that have been done on this, people who had an asymptomatic infection may not mount as strong of an immune response as people who had a symptomatic or severe infection. Again, that’s still an area of uncertainty, but the science in general right now seems to be pointing to that fact. So when you combine all those things together, we find ourselves in the position where we know that people who get vaccinated will benefit, and we just don’t know how much benefit and for how long the benefit will be in people who were previously infected, or have a positive antibody test without any confirmation of previous infections.

Of course, we don’t know yet how long immunity lasts from antibodies; the virus has been around for only about a year. But however long or short a period of time the virus has been around for, it’s still longer than the vaccine trial has been around. So we don’t know how long the antibodies from the virus itself will last, but we also don’t know how long the antibodies from the vaccine will last. Why are you confident that the antibodies from the vaccine will last longer than the antibodies from the virus itself?

There are several questions: One is the completeness of immunity, which is how well you’re protected. The second is the durability of immunity, which is how long your immunity lasts. And the third would be the issue of safety, and what is the better balance of safety.

So if you look at completeness of immunity, we have very good evidence from these clinical trials about the completeness of protection that you get from vaccination, at least with these two vaccine products that have been studied, one of which [Pfizer] is already authorized and one which will likely be authorized this week. [Ed. The second vaccine, from Moderna, was granted emergency use authorization by the FDA the day after our conversation.] So we have a pretty good understanding about completeness of the protection.

Regarding durability, you are absolutely correct. One area of uncertainty right now is we do not know how long you will be protected after immunization, because the only follow-up period so far has been two months — at least that’s what’s been published. So that’s all we know for sure from the clinical trials right now. So you’re absolutely correct that that remains an area of uncertainty.

The third question is the question of safety. And we know that for all the reasons that I just mentioned, we cannot be sure that people who have a prior antibody test actually mounted a durable and reliable immune response. Antibody tests all vary. There are multiple different antibody types that your body produces, and there are other forms of immunity that they have. We don’t really have enough evidence that the test that a person gets — which could be any of a number of different commercial tests on the market — actually indicates protection, known as a “correlate of protection.” Some of them might, but some of them may not. So when you look at the balance of safety measures, to me, and to all the public health experts who’ve looked at this topic, the balance is in favor of vaccination, even in people who have had prior infection.

I just want to add one more thing. This topic is actually looked at in both the Moderna and the Pfizer data: They actually enrolled people who had evidence of a prior infection. The problem is that the sample sizes are relatively small. But if you look at the Pfizer data, and I would have to confirm to get the exact numbers, it looks like in the subgroup that had a prior infection who got vaccinated, there were re-infections that occurred, in both the Pfizer study, and I also believe in the Moderna study as well. So this has been a topic that’s actually looked at; it’s just been looked at in smaller numbers. And in both of those, their conclusion was that people with prior infection would in fact benefit from vaccination.

[Ed.’s Note: According to the briefing document prepared for the FDA meeting regarding the Pfizer vaccine (page 28): “Only 3% of participants had evidence of prior infection at study enrollment, and additional analyses showed that very few COVID-19 cases occurred in these participants over the course of the entire study (9 in the placebo group and 10 in the BNT162b2 group, only 1 of which occurred 7 days or more after completion of the vaccination regimen — data not shown). The placebo group attack rate from enrollment to the November 14, 2020, data cut-off date was 1.3% both for participants without evidence of prior infection at enrollment (259 cases in 19,818 participants) and for participants with evidence of prior infection at enrollment (9 cases in 670 participants). While limited, these data do suggest that previously infected individuals can be at risk of COVID-19 (i.e., reinfection) and could benefit from vaccination.”

According to the briefing document prepared for the FDA meeting regarding the Moderna vaccine (page 25): “Only 2.2% of participants had evidence of prior infection at study enrollment, and there was only one COVID-19 case starting 14 days after dose 2 reported from this subgroup, which was in a participant in the placebo group. There is insufficient data to conclude on the efficacy of the vaccine in previously infected individuals.”]

Have there been any confirmed cases, worldwide, of someone who got the virus and got antibodies from the virus and subsequently got reinfected with the virus?

Yes, there have been a number — I’ve lost track of the latest count; it’s in the double digits of ones where they’ve verified it, as well as hundreds or maybe more of suspected ones.

We’re talking about worldwide.

Yes. But just so you understand this, it is incredibly difficult to actually document and prove reinfection, and the reason for that is that, number one, initial infection has to be confirmed with a molecular test, and we know the vast majority of people worldwide never have their infections confirmed. Number two, your second infection needs to be confirmed with a molecular test, which we know, again, doesn’t always happen. And the third thing is, both of those infections, we need to have the sample of your specimen available, so that we can perform something called sequencing, where we actually look at the RNA sequence of the virus and compare the first one to the second one, to verify that they are in fact distinct episodes of illness. [Ed. RNA is a molecule that carries genetic information.] That is actually very, very difficult to do scientifically. So I think the general consensus among scientists, all of us who have looked at this, is that reinfections within the first few months after an initial confirmed infection are very uncommon, and that people are generally protected for a few months after that first infection. After that, infections may occur, we just don’t know for sure how often they actually are.

You said that there’s no risk of death from the vaccine, whereas there is a risk of death from catching the virus. Some people feel that that’s exactly the point — that the reason health authorities are not going to publicly say they recognize antibodies as immunity is that then people will choose to become infected, which of course would cause a spike in the infection numbers, and some people will die. What’s your response to that? Is that a reason why health authorities are not publicly saying that antibodies provide immunity?

Again, the reason we’re not saying it is that the term “antibodies” is really a term that actually has a lot of nuance to it. And so again, I want to keep emphasizing, when people go out there and keep saying, “Well, I have antibodies,” you really need to understand immunology. We, as scientists, are not saying this because we’re trying to pull one over on you; it’s because the science of immunology is incredibly complex.

There are multiple proteins on the virus that develop antibodies, and your body develops various different types of antibodies, and there are other types of immunity called cell-mediated immunity. And all of those interacting together is still an area that needs to be understood. It is very likely that sometime in the next year we will understand better what is known as the correlates of protection. There was a study published in Science Magazine, within the past few weeks, that tried to answer this question — it’s from the same group at Harvard that developed the Johnson and Johnson vaccine, which is being evaluated in the clinical trial right now — it comes from studies in primates, and that is the first study that has looked at this question in a lot more detail to try to answer like, can you do a blood test that can really tell you whether or not you’re protected?

So I want to just keep emphasizing the fact that it’s because this term “antibodies” is not really precise enough to actually answer the question, which is, “Are you truly protected?”

And I know it’s very easy for people to look at a blood test and say, “Oh, the lab said it’s okay,” but there is an incredible amount of science that has to go into understanding what the blood tests actually mean.

And so I do believe that sometime within the next year we will probably have better tests to know for sure whether or not you have protection from your prior infection. But we just don’t have that right now at a population level. It will very likely come very soon; we just don’t have it at this moment.

As to the question about people actively infecting themselves: Absolutely, one of the reasons why people in the scientific community do not want to encourage there to be so-called “immunity passports” from prior infection is that it creates an incentive for people to get infected. And we know that infection comes with clear harms. Death is obviously the most severe harm that we don’t want at all. But there are a huge percentage of people — estimates anywhere from 25 to 30% of people — who have had an infection, who develop persistent symptoms. There are harms from being infected that are separate from death, that are also things that people would generally want to avoid as well.

Will any allowances be made in New York City for people who get the vaccine — for example, will they be allowed to not wear a mask — and if yes, will these allowances not be made for people who have antibodies from the virus?

Unfortunately, it’s too early for us to know the answer to that right now.

Right now, the current recommendation is that even if you have been vaccinated, you still need to continue the same safety measures that everybody else needs to do, which is to wear a mask, wash your hands, watch your distance. The reason for that is, again, another area of uncertainty: These studies did not evaluate in detail whether or not you are protected from never being a carrier of the virus. We know that from some anti-bacterial vaccines as well as from some anti-virus vaccines in animals, that there is the possibility that a vaccine can protect you yourself from getting sick, but it doesn’t necessarily protect you from having the virus, say, in your nose and spreading it to other people. So that’s another area of uncertainty that the people working on the vaccines and the CDC are trying to evaluate, and hopefully we’ll know more, but it’s too early to say what the policy will be like in the future when we relax these measures.

You’re saying that even those who have immunity due to the vaccine, it’s possible that they may still be able to spread the virus to others.

It’s just an area that we don’t know the answer to.

As the vaccine supply becomes more abundant, is anyone going to be forced to get it, for example, as a condition of going to school, or working for the city — and if yes, will antibodies be recognized? Or will the people who have antibodies still have to get the vaccine?

Again, this is just an area of uncertainty. At this moment, there is no policy that anybody is required to be vaccinated in any way or needs to document immunity for any type of work that they’re doing.

We’re in the middle of a pandemic. We are constantly learning things all the time. There may or may not be requirements in the future. It’s an area of uncertainty, but that is definitely not the policy right now.

Right now, with the vaccine being so scarce in the early days of its distribution, is anyone being allowed to get it even if they have antibodies, or are people with antibodies not allowed to get it in this early phase?

As I said before, the clinical trials included people who had prior infection. And the recommendation from everybody — at the federal government level, the state level and the local level — is that a history of prior infection should not either move you up or move you down in the prioritization schedule. In other words, if it’s your turn in line, you should get vaccinated.

—

rborchardt@hamodia.com