Well before the COVID-19 pandemic, there were plenty of questions about autoimmune diseases. The 80 or so that have been identified can affect nearly every part of the body with a bewildering variety of symptoms. The diseases can be difficult to diagnose, and it is unclear what causes them. The concept of a disorder that causes the immune system, which is designed to protect us from foreign invaders, to launch an attack on healthy organs and tissues is mysterious and frightening.
The uncertainty may lead people to see autoimmune disease as “an uncontrollable hobgoblin,” says Dr. Duane Pearson, a rheumatologist with the UCHealth Rheumatology Clinic – Anschutz Medical Campus and Professor of Medicine with the Division of Rheumatology at the University of Colorado School of Medicine.
The COVID-19 assault that began nearly three years ago understandably increased fears of infection among the tens of millions of Americans who suffer from diseases that disrupt their immune systems. The fear is justifiable, says Pearson’s rheumatology colleague, Dr. Kevin Deane. “While multiple factors like older age, heart and lung disease, diabetes and obesity can put people at higher risk for more severe COVID-19, people with autoimmune disease are also at greater risk of having more severe COVID-19,” Deane says.
The relationship between autoimmune disease and COVID
But Pearson and Deane emphasize that the connections between autoimmune disease and COVID-19 are complex. Far from being a stand-alone threat, autoimmune disease is generally part of a mosaic of risk for patients, they say. And they stress that patients can do much to protect themselves from infection while continuing to manage their conditions. The doctors recently spoke with UCHealth Today, offering their insights into the basics of autoimmune disease and treatment, as well as answering questions of keen interest, such as whether COVID-19 can cause autoimmune disease.
What is an autoimmune disease and what are some examples?
“The immune system is a set of processes in the body that do a lot of good things, like protect us from infections, heal wounds and clear cancer from the body,” Deane said. “Autoimmune diseases are a group of conditions where the immune system goes awry and attacks the body instead of protecting it.”
The list of autoimmune diseases is extensive – as is the damage they cause to tissue, muscles and organs. Deane pointed out a few of the more well-known culprits and their targets: rheumatoid arthritis (joints), Type 1 diabetes (pancreas), multiple sclerosis (nerves and brain) and lupus, which can cause multi-organ damage.
Why do autoimmune diseases put individuals at greater risk of contracting SARS-CoV-2, the virus that causes COVID-19, and also becoming severely ill?
In a person with an autoimmune disease, the immune system sees the enemy as existing within the body rather than as originating from foreign invaders like germs or toxins. That makes it an unreliable partner for protection from external threats, Deane said.
“In these patients, the immune system is probably not doing other jobs perfectly either, including fighting infection,” he said. “It is apparent that people with autoimmune disease have problems fighting off COVID. They are at higher risk for catching COVID in the first place and at higher risk for more severe COVID because their immune system can’t handle it once it occurs.”
Pearson also explained that proteins called interferons help the body fight off viral infections. In some patients with autoimmune disease, the interferon response may be ineffective. With the viral threat unaddressed, the body may launch an overly powerful inflammatory response. In the most severe cases, the result is a cytokine storm – a massive release of interferons and other immune system proteins that results in an assault far out of proportion to the original threat, with harm to organs resulting.
“If the precise mechanisms to fight infections are inefficient, the body’s response becomes less specific and broader and creates collateral damage,” Pearson said.
Can a weak autoimmune response to a COVID-19 infection in a person with an autoimmune disease be blamed solely on that condition?
No. Pearson stressed that many other factors may be involved. For example, autoimmune diseases often cause damage to multiple organs. The cumulative damage, rather than the mere fact that a person has an autoimmune disease, can lead to more severe outcomes from a COVID-19 infection, he said.
“When you look at studies [of autoimmune disease], they need to be adjusted for age, ethnicity and other factors we already know impact COVID outcomes, as does pre-existing kidney, lung or heart damage,” Pearson added. “People with other chronic conditions generally fare less well when they get infections such as influenza, so this is not a unique story to COVID-19.”
Rather than focusing solely on autoimmune disease as a risk factor for COVID-19, providers should make a “holistic evaluation” of each patient, Pearson said. He also advocated for focusing on “the meticulous primary prevention of COVID-19” in those with autoimmune diseases, “just as we should be for all other infections that we can prevent.”
Vaccination is a big part of that primary prevention. Should people with autoimmune disease be hesitant to get vaccinated against COVID-19?
No. “Throughout the pandemic, there has been messaging that because a patient with an autoimmune disease has a dysregulated immune system, they are somehow a special class and that we need to rethink how primary prevention should occur,” Pearson said. “Patients have been advised [by some] not to receive the COVID-19 vaccine. That’s wrong.”
Deane and Pearson declared that in fact, the COVID-19 vaccine “remains our most important tool to control both prevention of initial infection with COVID-19 and its severity.” They noted that the American College of Rheumatology (ACR) determined in 2021 that patients with autoimmune and inflammatory conditions are at higher risk of hospitalization and poor health outcomes from COVID-19 infection.
“Based on this concern,” they concluded, “the benefit of COVID-19 vaccination outweighs any small, possible risks for new autoimmune reactions or disease flare after vaccination.”
The ACR also has developed extensive guidelines and recommendations for safely administering COVID-19 vaccines to patients with autoimmune and inflammatory rheumatic diseases.
Can medications used to treat some autoimmune diseases increase the risk of severe COVID-19 infection and decrease the effectiveness of vaccines to protect against it?
Yes. Deane and Pearson cited three commonly used medications that “remain of greatest concern” in that regard. They are rituximab, mycophenolate mofetil, and prednisone and other steroids. “These three seem to be related to increasing the risk of getting COVID and may blunt the effectiveness of the COVID-19 vaccine,” Deane said.
Why is that?
The drugs work, in part, by suppressing the body’s infection-fighting B cells, which in some cases can abandon their normal protective role and contribute instead to producing autoantibodies that spur autoimmune disease, as well as inflammation.
“Because at baseline a person with autoimmune disease has an immune system that is out of control, we try to fix that by putting it back under control with these medications,” Deane said. However, in “modulating” the immune system to protect it from an internal attack, these medications may also make a patient more vulnerable to infection – including from the virus that causes COVID-19. In addition, the medications may reduce the levels of antibodies the body generates after receiving the COVID-19 vaccine.
What can be done about that?
“We always do our best to use the safest, lowest-risk medications to manage illness,” Pearson said. That means, in part, working to minimize patient exposure to prednisone and other steroids, which can cause a wide array of problems, including bone damage, hypertension, blood sugar increases and more. Those drugs have safer alternatives, he added, but the others do not. In those cases, the ACR guidelines address timing medication dosing and vaccinations “to get the maximum effect that we can” from the COVID-19 vaccines.
For example, individuals using drugs like rituximab may need to get a COVID-19 vaccine at certain times before or after their dose of rituximab; in addition, drugs like mycophenolate may be held for a period of time after a vaccine.
Deane and Pearson also noted that some medications, such as Evusheld, can offer protection, prior to exposure, to people who aren’t expected to respond well to the COVID-19 vaccine.
There are reports of people getting diagnosed with an autoimmune disease after contracting COVID-19. Is there a link?
There are a number of potential “triggers” for autoimmune disease. They include exposures to some chemicals and organic compounds, genetics, environmental pollutants like cigarette smoke and more. In fact, Pearson said, everyone who has been diagnosed with an autoimmune disease has had a trigger. Figuring out what that trigger was is the trick.
“Could COVID-19 be one of those triggers? Absolutely,” Pearson said. “But the vast majority of patients we have seen over the last four decades of rheumatologic care at some point didn’t have autoimmune disease, and then they did. Something triggered it, and for most of that time there was no COVID-19.”
In addition, Deane said, rheumatology specialists have long known that some infections can trigger autoimmune diseases. For example, bacterial infections that cause chlamydia and strep throat can lead to arthritis and rheumatic disease, respectively.
“Based on that, it would not be surprising if for some individuals, COVID-19 may be a trigger for an autoimmune disease,” Deane said. He added that patients with severe COVID-19 are at increased risk for developing blood clots which in some cases may be similar to an autoimmune disease called antiphospholipid syndrome, which also causes blood clots to form in previously healthy tissue.
“We also know of some people who have COVID and then have a full-blown autoimmune disease afterward,” Deane said. “It could be that they were predisposed and COVID is the trigger.” He emphasized that such cases are rare. “More studies are needed to understand these relationships further,” he concluded.
Is there evidence that links autoimmune disease to long COVID symptoms?
There is not yet a clear answer to that question. Patients with long COVID experience symptoms such as chronic fatigue, brain fog, shortness of breath, and a host of others four weeks or longer after the original infection. Pearson said it is still not known whether the symptoms of long COVID are the result of long-term disruption of the immune system or damage to organs, both of which are hallmarks of autoimmune disease.
“The answer is probably both,” he said. “But do the majority of long COVID patients have defined or documented autoimmune disease? The answer is no.” Nor is there data, he said, to support putting patients with long COVID symptoms on medications to modulate the immune system.
Pearson acknowledged that it is possible that some percentage of patients whose long COVID symptoms resolve will ultimately be diagnosed with an autoimmune disease, but that percentage has yet to be defined and is probably very small. “Research on that is in progress, and it is an important question to work through,” he added.
Aside from getting vaccinated, what are the best tips for people with RA and other autoimmune diseases to protect themselves against COVID-19?
Deane and Pearson urged patients to follow Centers for Disease Control and Prevention (CDC) guidance to reduce the risk for infection, get tested if they notice symptoms, seek medical care immediately if tests are positive and in general have an appropriate monitoring and treatment plan in place.
As they noted, patients who take medications that may blunt the response to a vaccine should work with their providers to optimize the timing of their shots or to determine if they are candidates for the protective medication Evusheld. Finally, patients who notice symptoms of COVID-19 infection early can get treatment with monoclonal antibodies, oral anti-viral medications and other therapies that can help to control symptoms, especially when they are given early.
“It’s important for people with autoimmune disease to understand that the best approach to not getting severe COVID is to not get COVID in the first place,” Pearson concluded.