Most people deciding to be vaccinated against Covid-19 can support their choice with clinical trial data, which has demonstrated the safety and efficacy of both the Moderna and Pfizer/BioNTech vaccines. But people suffering from autoimmune conditions, particularly those on immune-suppressing medications, are facing the decision of whether to receive a shot without the benefit of robust evidence-based guidance, as they were excluded from the Moderna, Pfizer/BioNTech, and AstraZeneca clinical trials.

In the absence of clinical trial data, how should people with autoimmune conditions approach the risk/benefit analysis of getting vaccinated? Here’s what several experts had to say.

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Autoimmunity is a big tent

Autoimmune (literally “self-immune”) disease happens when the immune system turns its aggression on the body’s own healthy cells and tissues. According to the American Autoimmune Related Diseases Association (AARDA), there are more than 100 known autoimmune conditions. Some, such as rheumatoid arthritis, Hashimoto’s thyroiditis, lupus, multiple sclerosis, type 1 diabetes, and inflammatory bowel disease are relatively common, while others are rare and hard to diagnose.

Roughly 24 million people in the United States have at least one autoimmune condition, according to the National Institutes of Health (NIH), and many have more than one. An estimated 41 million people have auto-antibodies, molecules that indicate a risk of developing autoimmune disease.

Covid-19 vaccine clinical trials did involve some people with autoimmune conditions but excluded others. Autoimmune diseases vary as much in severity as they do in type, ranging from pesky to life-threatening. Some, such as Hashimoto’s thyroiditis, are targeted on a single area (like the thyroid) and may be manageable without medications. People in this category were involved in the vaccines’ clinical trials. (Though Patrick Hanaway, MD, a family physician in Asheville, North Carolina, and senior adviser to the CEO of the Institute for Functional Medicine, notes that neither Moderna nor Pfizer segregated those with autoimmune disease in their reported data to gauge any differences in vaccine response — data that could be useful to clinicians and researchers alike.)

People suffering from more systemic autoimmune conditions, such as lupus and Crohn’s disease, which often require immune-suppressing medications to manage symptoms, were excluded from the vaccine trials.

This isn’t unusual. People on immunosuppressive therapies, such as disease-modifying antirheumatic drugs (DMARDs) and biologics, are frequently excluded from clinical trials. Manufacturers generally determine a vaccine’s baseline safety and efficacy in the general public before evaluating any differences in other, more challenging populations. The response of these populations is then observed in phase 4, or “post-marketing,” surveillance, after the vaccine receives FDA approval.

But the lack of clinical trial data, while not unusual, means that people with autoimmune conditions may have concerns about how a Covid-19 vaccine might affect them. These concerns fall into two major categories: safety and efficacy.
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Are the Covid-19 vaccines safe for people with autoimmune conditions?

“Because people on immunosuppressants were not in the trials, we’re left with no direct data to answer that question,” says Gregory Poland, MD, a vaccinologist at Mayo Clinic in Rochester, Minnesota, and the director of Mayo Clinic’s Vaccine Research Group. “So we ask, ‘Is there a biologic mechanism by which any vaccine would cause mischief or a problem for people with autoimmune disease?’”

There’s one category of vaccines for which the answer is yes: live vaccines that use an attenuated or weakened live virus. Examples include measles, mumps, and rubella (MMR); varicella; and intranasal flu vaccines. Because these vaccines use a live virus, people with compromised immune systems or on immunosuppressive drugs may be at increased risk of adverse events after receiving them. (Live vaccines should also not be given to pregnant women, because they may be harmful to the baby, according to the Centers of Disease Control and Prevention.)

“My general recommendation is to get the vaccine. Even if you may not have full protection, it’s probably still better to get it than not to get it.”

Importantly, though, none of the approved or expected-to-be-approved-soon Covid-19 vaccines fall into this category. Both the Moderna and Pfizer vaccines use a new vaccine technology that relies on messenger RNA (mRNA) — essentially slipping building instructions for the SARS-CoV-2 spike protein into the body so it can construct it and learn how to recognize and neutralize it when and if the real thing appears.

Is there any other way in which a vaccine could cause mischief for people with autoimmune disease?

“One concern is whether a vaccine can trigger a flare of autoimmune disease or cause autoimmune disease in someone who’s susceptible,” says Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health in Bethesda, Maryland. Autoimmune flares are the sudden and severe onset of symptoms such as fatigue, joint pain and swelling, fever, swollen glands, skin problems, and digestive issues.

“Studies looking at large datasets have not conclusively been able to say that getting a vaccine can trigger an autoimmune disease or cause a flare, though anecdotal reports are there,” Hasni says.

Poland, whose Mayo Clinic Vaccine Research Group has performed extensive NIH-funded research investigating the genetic drivers of viral vaccine response, says he’s seen no evidence for vaccines exacerbating autoimmune disease — though his research has not included the new mRNA vaccine platforms.
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So, is there anything else about mRNA vaccines to be concerned about?

In a 2018 paper in Nature Reviews Drug Discovery, Drew Weissman, MD, PhD, of the University of Pennsylvania and a pioneer of mRNA technology, wrote, “A possible concern could be that some mRNA-based vaccine platforms induce potent type I interferon responses, which have been associated not only with inflammation but also potentially with autoimmunity.”

Some autoimmune diseases, including lupus, are shown to be driven by a high interferon response in the body, Hasni says. So, stimulating that pathway — as mRNA vaccines do — could theoretically cause a flare.

But at this point, that concern remains speculative. “Could you imagine a type 1 interferon response that could exacerbate an autoimmune disease? Theoretically, yes, but it hasn’t been observed,” Poland says. “I’d say someone with an autoimmune disease would be at much higher risk from complications of being infected with Covid-19.”

“If you’re already in [an autoimmune] flare where your immune system is going haywire, it can make the flare worse. In general, it’s better to wait until the flare is under control and things have calmed down.”

Hasni agrees. “If the benefit of a vaccine is that it can protect you from a viral infection that can be deadly or make you really sick, and the risk is a disease flare that can be controlled effectively with medications in most patients, then the vaccine gives a greater benefit.”

Both Hanaway and Hasni say that while the benefit of receiving a Covid-19 vaccine outweighs the risk of a possible autoimmune flare, people with autoimmunity should do everything possible to ensure they’re not in an active flare state when they receive the vaccine.

“When you give a vaccine, it revs the immune system,” Hasni explains. “If you’re already in [an autoimmune] flare where your immune system is going haywire, it can make the flare worse. In general, it’s better to wait until the flare is under control and things have calmed down.”

“As a clinician, I don’t want my patients with autoimmune disease to get the vaccine while having an active flare,” Hanaway says. “Let’s decrease inflammation and put the body in a state where it can have a useful immunologic reaction to the vaccine.”

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For Hanaway, that means using integrative dietary, supplemental, and stress-reduction tools to help reduce overreaction of the immune system and get the body into a more quiescent state. Hasni adds that depending on the condition and the severity of the flare, steroids may also be needed on a short-term basis to calm things down before a person receives a vaccine.

The bottom line on the safety of Covid-19 vaccines for people with autoimmunity: “Until we have data to the contrary, for the majority of people with autoimmune disease, their risk of complication from infection is far higher than the observed teeny risk attributable to any of the Covid vaccines,” Poland says.

Hanaway agrees, adding that the potential for SARS-CoV-2 infection to lead to post-Covid-19 syndrome (lingering symptoms suffered by so-called long-haulers) is all the more reason for people with autoimmune disease to opt for vaccination.

Are Covid-19 vaccines effective for people with autoimmune conditions?

The other area of concern: Can immunosuppressive drugs that help autoimmune patients manage their symptoms affect the body’s ability to mount a robust immune response to a Covid-19 vaccine?

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