Why Immunosuppressants Affect COVID Vax Response
Our expert weighs in on COVID vaccine efficacy in the chronic population, and whether masks are still a must.
This summer has felt deceptively like a return to pre-pandemic life: people are socializing, concerts and sporting events are coming back, and restaurants are gradually bumping up their indoor dining capacity. As more Americans get vaccinated, it is getting slightly easier to go out in public without that looming anxiety about catching COVID-19.
Unfortunately, immunocompromised folks can’t breathe that sigh of relief just yet. Much is still unknown about the efficacy of COVID vaccines in this population, and several recent reports have suggested that some chronic patients (specifically, those on immune-suppressing medications) may generate fewer antibodies after vaccination. As a quick reminder, antibodies are proteins produced by your immune system that jump in to fight off a foreign invader—in this case, the virus that causes COVID-19.
On May 5, JAMA published a study looking at antibody responses of organ transplant patients after two doses of the mRNA COVID vaccine. Researchers found that only 54% of patients developed antibodies after the two-dose series. This sounds scary, and it is. But some experts are already proposing a potential solution. On June 15, a study in the Annals of Internal Medicine, conducted by scientists at Johns Hopkins, suggested that a third “booster” shot of mRNA vaccine may improve the antibody response in patients who weren’t adequately protected after two doses. (It’s worth noting that this is not officially approved by the CDC yet and is only being done in clinical trial settings.)
What does all this mean for the chronic community? Should high-risk folks with autoimmune conditions continue wearing masks and social distancing, even as restrictions ease up? When will we know more? We took these questions and others to Ethan Smith, PharmD, clinical pharmacist at Cedars-Sinai in Los Angeles. Here are some of his biggest takeaways:
HC: We’ve seen some recent reporting suggesting that immunocompromised people may not be generating adequate antibodies in response to the COVID vaccine. Can you give me the latest update on what we know now?
Ethan Smith: There is still a lot we don’t know … but the big picture is, you’re absolutely right: There are a number of different types of immunosuppressant presentations that potentially may not mount an antibody response to the vaccines.
The important thing to stress here is that it’s a spectrum. Certain diseases and medications are a lot more immunosuppressive than others, and it’s a blanket statement that all people who could potentially be considered immunosuppressed won’t mount a vaccine response. Some will mount the vaccine response, and we have data to suggest that is the case. Some just don’t do it as well, and some unfortunately don’t do it at all.
One other thing to focus on is that a lot of these news reports focus on antibody response to the vaccine. The immune system is exceedingly complex, and when we talk about the [efficacy] of a vaccine, there are really two major components of the immune system that are involved. There’s the humoral immunity, which is that antibody response. Then there’s also cellular immunity, which is certain T-cells such as CD8+ that are particularly important [in activating the body’s immune response against] COVID. We don’t have as much data on CD8+ T-cell response as we have on antibodies.
So, the level of antibodies is not a perfect correlation to COVID protection. Even if somebody doesn’t have antibodies or they have lower antibodies [in response to the vaccine], that doesn’t mean that they are not immune through these other mechanisms, such as CD8+ T-cells. That is where we really need more data: to see how that cellular response to vaccines is occurring in these patients, in addition to their antibodies, before we have a complete picture.
HC: Why is it that immunocompromised people sometimes generate lower antibodies in response to the vaccine?
Ethan Smith: When we talk about antibodies, we are looking at numbers. It’s what we call an antibody titer. To simplify: the higher the titer, the more antibodies we have. In theory, the more antibodies you have, the more protected you are [from infection]. But we see with other vaccines that there is usually a minimum level of antibodies, and once you exceed that number, you are considered protected [from the virus or disease]. That’s different from vaccine to vaccine, but we don’t have that information yet for COVID.
For example, in a patient who is not immunocompromised and is otherwise healthy, their antibody titer might be 1,000. In somebody who is immunocompromised, their antibody titer might be only 100. It’s ten-fold lower. But if that minimum level of protection is only an antibody titer of 10 or 50, both of those patients will have adequate protection from the vaccine.
We just don’t know yet what that minimum threshold for antibody protection is. That’s the other piece of the picture we are missing at this point.
HC: OK, so there’s not a clear correlation between lower antibodies and level of protection from the COVID vaccine?
Ethan Smith: Right, exactly. A lower antibody count doesn’t mean no protection.
HC: What does this mean for a “return to normal” for immunocompromised folks? Should they continue behaving as if they have not been vaccinated?
Ethan Smith: The best place to go for information is to your physician, because like I said, this is a spectrum. Somebody with rheumatoid arthritis who is on a mild immunosuppressive regimen will probably mount a better response to the vaccine than will somebody with a blood cancer who is actively getting chemotherapy. That latter patient is certainly more immunosuppressed.
Physicians caring for these patients are the best resource to determine what the process should be going forward. There is also a lot of guidance from various societies that deal with these immunocompromising conditions. Two examples are the National Comprehensive Cancer Network (NCCN) and the American College of Rheumatology (ACR), which both have guidance in terms of vaccine timing, how to handle immunosuppression, and what social distancing and masking should look like in these immunosuppressed patients who have been vaccinated.
In many of these society recommendations, until we have further data on exactly how these vaccines are performing in immunocompromised patients, there is going to be some component of masking and social distancing still recommended.
HC: Some experts have floated the idea of a third ‘booster shot’ to help ramp up the antibody response in people who didn’t mount an adequate response to the first two doses. This hasn’t been widely tested or studied, but a recent Johns Hopkins study suggested it might be a useful tool. What do you think about this?
Ethan Smith: I think that concept is reasonable, but I don’t think we have enough data to suggest exactly who or when or how. Does every immunocompromised patient need a booster dose, or is it just a subset of immunocompromised patients who would need one?
So far, some immunosuppressants do not appear to impact the antibody response as much as others. This is exactly why we need more data on this subject, so we can identify the right cohort of immunosuppressed patients to target for booster doses. This is also why it would be helpful to have a minimum antibody level as a correlate of protection—if immunosuppressed patients mount a lower vaccine response compared to healthy individuals, but still have an antibody level above that yet-to-be established threshold, maybe we can forgo a booster dose, because they would still be considered protected.
Overall, the booster doses appeared to be very safe in the Hopkins study … so I think booster doses will be critically important for these immunosuppressed patients. Hopefully, additional data in the coming months will inform us exactly which patients should be targeted for additional booster doses.
HC: When can people with chronic conditions expect to know more about whether the COVID vaccines are working for them?
Ethan Smith: That’s a good question that I don’t have a clear answer to. There is a lot of interest in the medical community … and as we get more people vaccinated, we are seeing these large population-based studies reporting on real-world vaccine efficacy. So, I don’t think it’s in the distant future, but I can’t say for sure whether it’s going to be two months, four months, or six months from now.
HC: If any of our chronic readers want to help with the ongoing research on this topic, what can they do?
Ethan Smith: That’s a very altruistic thing for these types of patients to do. Depending on where they are receiving care [and whether] their physician is an investigator in this type of study, they can simply ask. Say, “I’m sure you see a lot of patients like me. Are you looking into vaccine response in your patients? If so, I’d like to volunteer for a blood sample to check my antibodies.” It’s just a matter of asking.
HC: Is there anything else you’d like to share?
Ethan Smith: Keep taking your immunosuppressant medications as prescribed until you have a conversation with your physician. A lot of these medications really are a gift of life. So, keep taking them, talk to your physician, and work with them to come up with a plan for how to get vaccinated.
Smith offers one more suggestion for the friends and loved ones of the chronic community: Get vaccinated. If you’re nervous, think about the other people in your life who can benefit from you taking this important step. “By getting vaccinated, they help to protect these patients who may not otherwise respond as well to the vaccine,” Smith says. “We can help protect our friends and neighbors by getting vaccinated ourselves.”
Organ Transplant Recipients & Antibody Response: JAMA. (2021.) “Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients.” https://jamanetwork.com/journals/jama/fullarticle/2779852
Booster Shots for Immunocompromised Patients: Annals of Internal Medicine. (2021.) “Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series.” https://www.acpjournals.org/doi/10.7326/L21-0282