COVID-19 Can Cause Autoantibodies Seen in Autoimmune Conditions: Here’s What We Know So Far

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Over the past year, researchers have been studying the link between COVID-19 and the development of autoantibodies.

Unlike antibodies that fight off viruses and foreign invaders, autoantibodies mistakenly target your own tissues or organs. They are associated with autoimmune diseases such as rheumatoid arthritis and lupus.

Although research is still emerging, currently available evidence has highlighted a few key points of interest to people with autoimmune and inflammatory conditions.

• Pre-existing autoantibodies may pose a risk factor for severe COVID-19, but this is not definitively proven yet.
• Researchers believe COVID-19 (particularly severe COVID-19) can lead to the development of new autoantibodies.
• These new autoantibodies are potentially pathogenic — meaning they could directly cause harm in our bodies, such as blood clotting, vasculitis (blood vessel inflammation), and tissue damage.
• Autoantibodies may play a role in long COVID symptoms.

You may be worried about developing autoantibodies if you’ve had COVID-19 — and what that would mean for your risk of severe COVID-19 or worsened autoimmune disease. Here’s what you should keep in mind for two scenarios.

1. If you have an autoimmune disease: Although some preliminary data suggests pre-existing autoantibodies may raise the risk for severe COVID-19, more research is needed to confirm this, and researchers say there’s no major cause for concern right now. What’s more, research shows that the risk of developing severe COVID-19 depends on several factors (age, heart and lung conditions, severe obesity, etc.). The role that autoantibodies may play is still being studied.

2. If you have an autoimmune disease and have had COVID-19: Developing new autoantibodies after having COVID-19 doesn’t directly translate to new or worsened autoimmune disease. There are many different types of autoantibodies, and those that are appearing in people who have had COVID-19 may not be the same as those present due to your underlying condition.

If you’ve already had COVID-19, particularly a mild to moderate case, you likely don’t need to be concerned. “I think it’s just too early to know if the autoantibodies are going to be clinically meaningful,” says PJ Utz, MD, Physician Scientist in Immunology and Rheumatology at Stanford University.

Here’s some promising news: The prevalence of autoantibodies in COVID-19 patients is prompting new research on autoimmunity generally, which researchers believe will accelerate the body of knowledge and future treatment for the current community of people with autoimmune and inflammatory conditions.

For example, researchers have known for years that not everyone who develops autoantibodies goes on to develop autoimmune disease, but they’re not sure why that is. They’ve hypothesized that there are environmental triggers that cause the disease to take hold, with bacterial or viral infections high on the list of potential autoimmune disease triggers.

“This is particularly exciting for us in the autoimmune field, because it gives us a once-in-a-lifetime opportunity to actually see if or how a virus can trigger autoimmunity,” says Dr. Utz.

Here’s what the research on COVID-19 and autoantibodies says so far, and what it may mean for you if you live with autoimmune disease.

Autoantibodies and Their Role in COVID-19

COVID-19 may cause autoantibodies for a number of reasons. They could appear because of an inflammatory immune response — in which the body begins to attack its own cells — that occurs in certain patients predisposed to autoimmunity.

It may also be due to something called molecular mimicry, in which there’s cross-reactivity because certain proteins in the virus look like our own body’s proteins. This causes your body to produce autoantibodies that can attack your own cells instead of the coronavirus.

Researchers believe some autoantibodies caused by COVID-19 are likely to be pathogenic, meaning they could directly cause harm in our bodies, such as clotting, vasculitis (blood vessel inflammation), and tissue damage.

In a January 2021 preprint study (meaning it hasn’t yet been peer-reviewed), researchers measured levels of different autoantibodies in 147 patients hospitalized for COVID-19 and compared the samples to those of 41 healthy controls.

They found autoantibodies in about 50 percent of COVID-19 patients (which the researchers concluded are almost certainly new autoantibodies), but in less than 15 percent of healthy controls. Even healthy people make autoantibodies, but typically in small amounts, and they don’t typically appear to target the immune system or cause damage.

“With COVID-19, patients have autoantibodies that recognize proteins we see in diseases like scleroderma, and we think that’s abnormal,” says Dr. Utz, one of the authors of the study. “They just shouldn’t be there. But the only way to know whether or not patients will go on to develop these diseases later on is to study literally hundreds of thousands of people and to do large epidemiology studies.”

The researchers also measured anti-nuclear antibodies (ANAs), a type of autoantibody present in diseases such as scleroderma, lupus, and Sjögren’s syndrome, in one of their cohorts (which totaled 73 patients). Of these patients, 25 percent had ANAs. Again, it will take years to determine if these patients go on to develop actual autoimmune disease.

The researchers found anti-cytokine antibodies (another type of autoantibody) in 80 percent of a cohort of 51 hospitalized COVID-19 patients — but not in patients with mild COVID-19 or healthy patients.

Anti-cytokine antibodies have implications for COVID-19 because they block cytokines, which are immune system proteins that interfere with viruses. “If you block the interference factors, you can’t get rid of the virus as easily and you may have a worse outcome,” says Dr. Utz.

Other research has also shown that some autoantibodies present in COVID-19 could also play a role in blood clotting, a common complication of COVID-19.

In a November 2020 study published in the journal Science Translational Medicine, researchers measured blood samples from 172 patients hospitalized with COVID-19. They found that 52 percent had antiphospholipid antibodies (a type of autoantibody), and two-thirds of these were detected at moderate to high levels.

The antiphospholipid antibodies detected in hospitalized COVID-19 patients were found to cause clots in animal models.

It’s important to note that samples were taken from the severest end of the COVID-19 spectrum, and that a relatively small percentage of people end up in the hospital with this type of severe disease course, says researcher Jason Knight, MD, Academic Rheumatologist at Michigan Medicine.

“I think it’s unknown, at least by me, how likely milder forms of COVID-19 are to trigger this type of autoantibody response that we see in severe COVID-19,” Dr. Knight says.

The participants in the study did not have a history of autoimmune conditions, and the researchers suspect that the detected autoantibodies were not present before hospitalization with COVID-19.

Autoantibodies and Long COVID

In a December 2020 preprint study, researchers screened a group of 194 COVID-19 patients for autoantibodies against 2,770 proteins. They found that COVID-19 patients exhibited dramatic increases in autoantibodies compared to uninfected controls, and that those autoantibodies affected immune system function.

The more severe COVID-19 a patient had, the greater the likelihood that the patient would develop autoantibodies.

“From our cohort, we see autoantibodies that are transiently present, meaning that they are induced or appear after the patient contracted the virus, but we also see the more persistent type,” says Tianyang Mao, BS, an author of the study and a researcher at Yale School of Medicine. “These autoantibodies can potentially act as drivers for some of the long COVID diseases that we are increasingly observing from patients.”

Long COVID is a term used to describe the syndrome that causes long-hauler symptoms in people who have recovered from COVID-19. The National Institutes of Health (NIH) calls long COVID Post-Acute Sequela of COVID-19 (PASC).

The researchers are currently conducting follow-up studies to test the hypothesis that autoantibodies may play a role in PASC.

What This Research Means for Autoimmune Patients

Overall, Dr. Utz points out there are several things we still don’t know:

• If having pre-existing autoantibodies could definitely cause more severe COVID-19
• The true prevalence of autoantibodies in COVID-19 patients
• Whether or not COVID-19 patients who get autoantibodies will go on to develop autoimmune diseases (determining this will require very large epidemiology studies over a long time)
• Exactly how this might affect patients with autoimmune diseases like lupus or scleroderma who get infected with COVID-19
• If there is a definite link between autoantibodies and long COVID

It’s worth noting that many autoimmune patients are often already on certain medications that counteract the abnormal response of autoantibodies, which may be protective.

“Some immunosuppressive medications may increase the risk of having a hard time with COVID-19 — but at the same time, there are certain immunosuppressive drugs that we actually use to treat COVID-19, including dexamethasone,” says Dr. Knight. “Or for instance, the fact that people with antiphospholipid syndrome are on blood thinners to begin with may give them some protection against blood clots, and they may be in better shape than someone else who is not already on blood thinners.”

Your best course of action is to continue taking your medication as prescribed by your doctor, get the COVID-19 vaccine, and to continue to follow mitigation efforts (here’s what immunocompromised people should know about the CDC recommendations for fully vaccinated people).

You can also look forward to more research that could benefit the autoimmune community on the horizon.

“I think the attention this has gotten will lead to more funding for autoimmune research in general and get us closer to that dream of precision medicine for autoimmunity,” says Dr. Knight.

Right now, finding the right drug for each patient involves trial and error. More research that helps doctors understand the mechanics and timeline of autoimmune disease better could allow them to combine factors like epigenetics (the study of how your behaviors and environment affect how your genes work), gene expression in blood, and gene expression in tissues to develop new risk prediction models and determine the right drug for each patient.

“More people have probably heard of autoimmune disease now than before COVID-19,” says Dr. Knight. “The pandemic has been a very, very bad thing, but I think we’re going to learn things about autoimmunity from COVID-19 that we will then be able to take back to our regular clinics.”

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