Study: Autoimmune Disease Patients Have a Slightly Lower Antibody Response to the COVID-19 Vaccine

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Many people who are immunocompromised because of medical conditions and medications — including those with autoimmune diseases — have been anxiously waiting for more data to shed light on how effective the COVID-19 vaccines might be for them.

Now, a new pre-print study (meaning it hasn’t been peer reviewed yet) posted on medRxiv is adding to the body of research available to draw answers from. In an interim analysis of an ongoing observational study that launched April 14, 2021 across Western Pennsylvania, researchers observed 107 healthy health care workers and 489 immunocompromised patients who had been fully vaccinated against COVID-19. Those with a history of COVID-19 infection were excluded from the study.

The researchers collected blood from participants to measure the presence of antibodies against the SARS-CoV-2 spike protein, which causes COVID-19. Antibodies are proteins that stop pathogens like SARS-CoV-2 from infecting your cells. They’re produced by the immune system after an infection or vaccination.

Compared to the healthy health care workers, seropositivity (which indicates the presence of antibodies) was lower among immunocompromised patients with solid organ transplant, autoimmune disease, hematological malignancies (cancers that affect the blood, bone marrow, or lymph nodes), and solid tumors.

Here’s how the groups compared:

• Healthy health care workers: 98.1% had antibodies
• HIV patients: 94.6% had antibodies
• Autoimmune patients: 83.8% had antibodies
• Solid tumor patients: 82.4% had antibodies
• Hematological malignancy patients: 54.7% had antibodies
• Solid organ transplant patients: 37.2% had antibodies

Cancer patients who were receiving radiation therapy and other people who were taking certain specific medications, such as antimetabolites for transplant (such as mycophenolate) and anti-CD20 monoclonal antibodies (medications like rituximab) for autoimmune disorders, were less likely to have antibodies after receiving the COVID-19 vaccine.

The researchers also took blood from some of the participants (30 health care workers and 36 immunocompromised patients) and tested it to see how well it could neutralize SARS-CoV-2. Neutralizing a virus means its ability to replicate — and therefore its infectivity — is decreased.

The ability to neutralize the virus was strongly linked to patients’ antibody levels, as measured by an independent FDA-approved test. This provided additional evidence that people who do not produce antibodies are at a greater risk of COVID-19 infection and that there’s a connection between antibody levels and the ability to neutralize the virus.

However, there are some important limitations to these findings. For instance, experts still need to learn more about the degree of the antibody response in immunocompromised patients who were seropositive. They also don’t know with certainty how well antibodies in immunocompromised patients may effectively neutralize SARS-CoV-2.

Plus, there isn’t an established level of antibodies that is connected to COVID-19 prevention yet (in fact, here’s why experts urge against testing for antibodies after your COVID-19 vaccination). Even if you receive a negative antibody test, your immune system has more tools than just antibodies available to fight off the virus, including T cells and other immune cells. And of course, immunosuppressant medications can have varying effects on immunity from person to person.

Still, the results do show that not everyone responds to the COVID-19 vaccine in the same way — and some groups would likely benefit from continuing to practice mitigation efforts.

Research like this is also very important in discussions about whether an additional booster dose is needed for people on certain medications or with certain medical conditions.

“Our findings demonstrate the heterogeneity of the humoral immune response to COVID-19 vaccines based on underlying immunosuppressive condition and highlight an urgent need to optimize and individualize COVID-19 prevention in these patients,” note the researchers. “These findings also have implications on public health guidance, particularly given revised Centers for Disease Control and Prevention recommendations permitting vaccinated individuals to abandon masking and social distancing in most settings.”

Of course, the U.S. Centers for Disease Control and Prevention (CDC) also note that it’s important for immunocompromised patients to speak to their doctor before stopping COVID-19 mitigation efforts. Here’s why you shouldn’t toss away your mask yet if you’re immunocompromised, even if you’re fully vaccinated.

“At this point, clinical advice does not change for immunocompromised people, whether an antibody test is positive or negative,” said researcher Ghady Haidar, MD, in a press release from the University of Pittsburgh Medical Center. “They should still wear a mask in public, practice social distancing, get vaccinated and encourage those around them to be vaccinated. A positive antibody test does not give us certainty that they are protected against the virus, and the risk of COVID-19 causing serious complications and death still exists.”

Previous research has shown that autoimmune patients may not be as protected by the COVID-19 vaccine, even though experts agree it’s still very important to get vaccinated (after all, some protection is better than none).

For instance, a May 2021 study showed that methotrexate may hamper the immune response to the COVID-19 vaccine. Methotrexate is a disease-modifying antirheumatic drug (DMARD) that’s often prescribed to those recently diagnosed with rheumatoid arthritis. While more than 90 percent of healthy subjects and inflammatory disease patients on biologic treatments had robust antibody responses, only 62 percent of those on methotrexate achieved an adequate response. What’s more, patients taking methotrexate didn’t have an increase in CD8+ T cell activation, another element of the immune system that might fight off the virus.

Other research has shown that rituximab can lead to worse COVID-19 outcomes and a diminished response to the COVID-19 vaccine. Rituximab is used to treat rheumatoid arthritis and interferes with antibody production.

In the United States, a panel of independent advisers to the Centers for Disease Control and Prevention have been discussing if autoimmune patients should receive a third dose of the COVID-19 vaccine to boost their immunity, reports NBC News. Recently, Israel approved COVID-19 booster shots for the immunocompromised.

Other vaccines require a different dosing schedule for the immunocompromised. For instance, the human papillomavirus vaccine involves two doses, but those with weakened immune systems receive three doses.

Although more data is needed, it is promising that nearly 84 percent of autoimmune patients developed antibodies in response to the vaccine in the newest study. This underscores the importance of getting vaccinated, even if you do have an underlying condition. Vaccines not only prevent COVID-19, but also severe outcomes like hospitalization and death.

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