Long COVID and Autoimmune Disease: How They’re Connected

Executive Summary

• Most individuals recover from COVID-19 infection within a few days to weeks, but about 6% of those infected experience symptoms that persist for months or years due to a condition known as long COVID.
• Even though research is still evolving, long COVID is suspected to arise from multiple mechanisms, including lingering viral remnants, tissue damage, and immune dysregulation.
• Although long COVID is not an autoimmune disease in the traditional sense, many of its symptoms overlap with those caused by autoimmune conditions, making diagnosis and management more complex across the board.
• To support long-term health after COVID-19, patients should prioritize proactive care and monitor their symptoms—the Autoimmune Association can connect you with helpful resources.

Exploring Long COVID’s Effects on the Immune System

In the years following the initial global spread of COVID-19, a new, tangential health challenge has surfaced: long COVID, a post-viral, infection-associated chronic condition (IACC).

While many people recover from a SARS-CoV-2 infection within days or weeks, 6% face long COVID, meaning they continue to experience symptoms for months or sometimes years. This condition has raised important questions about how viral infections can affect the body over time, especially in the world of autoimmune research.

Keep in mind, long COVID is not officially classified as an autoimmune disease because it is suspected to arise from multiple mechanisms, rather than solely an immune system attack on self-tissues. However, in addition to potential causes such as lingering viral remnants and tissue damage, it may also result from immune dysregulation, drawing a strong connection between long COVID and autoimmune disease.

Although research is still evolving, the guide below breaks down what researchers currently understand about long COVID, how it affects the immune system, and what patients should know moving forward.

What Is Long COVID?

Long COVID is a chronic condition that follows an initial SARS-CoV-2 infection. Unlike an acute COVID-19 infection, long COVID, by definition, lasts at least 3 months. During this time, patients may experience a wide range of symptoms that fluctuate in severity.

Common Symptoms of Long Covid

Living with long COVID looks different for everyone; nonetheless, most people report a combination of symptoms, such as:

• Chest discomfort
• Shortness of breath
• Persistent fatigue
• Brain fog or difficulty concentrating
• Joint and muscle pain
• Sleep disturbances

For some individuals, long COVID symptoms improve over time, while they worsen or remain steady for others; this condition varies widely in severity and presentation.

Why Do Symptoms Persist?

The exact reason symptoms linger is still being studied. However, researchers believe that in some individuals, the body’s response to the virus does not fully reset after the infection clears—certain immune processes may remain active, contributing to ongoing inflammation or dysfunction.

How the Immune System Responds to COVID-19

To understand the connection between long COVID and autoimmune disease, it helps to look at how the immune system typically responds to viral infections. The table below explores what happens when a virus encounters a normal immune response versus a dysregulated one.

COVID-19’s Unique Impact

COVID-19 appears to affect the immune system in complex ways. For example, it can trigger strong inflammatory responses and, in some cases, disrupt normal immune signaling. This disruption may help explain why some people develop persistent symptoms, and why researchers are asking whether long COVID can cause autoimmune disease is a valid concern.

The Autoimmune Link: What Researchers Are Finding

During the Autoimmune Association’s 2023 Autoimmune Community Summit, Nina Luning Prak, MD, PhD, who is the chair of the Autoimmune Association’s Medical and Scientific Advisory Council, mentioned long COVID while exploring the 5 most promising areas in autoimmune research. 

Dr. Prak raised the question of whether and how long COVID perpetuates a loss of self-tolerance, which is the immune system’s ability to identify and avoid attacking the body’s own cells and tissues—in other words, can long COVID cause autoimmune disease?

The answer is not yet definitive, but there are compelling connections that you can explore in the sections below.

Viral Triggers and Autoimmunity

It is well established that viral infections can sometimes trigger autoimmune responses. This occurs when the immune system, initially activated to fight an infection, begins to target the body’s own tissues—COVID-19 may act as a similar trigger in some individuals.

Key Theories

Researchers are exploring several mechanisms that could link long COVID to autoimmune activity; some examples include:

• Molecular mimicry – Viral proteins resemble the body’s own tissues, causing the immune system to attack both mistakenly.
• Immune overactivation – A strong immune response during infection may fail to shut off properly, resulting in ongoing inflammation.
• Autoantibody production – The body may produce antibodies that target its own cells, contributing to autoimmune-like symptoms.

Emerging Evidence

Akiko Iwasaki, PhD, a professor of immunobiology at the Yale School of Medicine, has led one of the many research teams that have provided evidence of a connection between long COVID and autoimmunity. Iwasaki’s team detected significant levels of autoantibodies in people who were infected with SARS-CoV-2, and these autoantibodies are key diagnostic and clinical markers of autoimmune diseases.

While this does not mean long COVID is definitively an autoimmune disease, it strengthens the connection between long COVID and autoimmune diseases in general, supporting continued research in this area.

Overlapping Symptoms and Conditions

One of the main challenges in understanding this post-viral IACC is the overlap between long COVID and autoimmune symptoms. 

Many long COVID autoimmune symptoms mirror those seen in conditions like rheumatoid arthritis and other autoimmune joint disorders, or some neurological autoimmune conditions like multiple sclerosis.

Some examples of commonly overlapping long COVID and autoimmune symptoms are:

• Fatigue
• Joint pain
• Muscle aches
• Cognitive issues (brain fog)
• Inflammation

Diagnostic Complexity

Because of this overlap, it can be difficult to determine whether a patient is experiencing long COVID, a new autoimmune condition, or a combination of both. This complexity highlights the importance of finding the right doctor for a thorough medical evaluation and ongoing monitoring.

Potentially Linked Conditions

Researchers are still investigating whether COVID-19 may be associated with the development of certain autoimmune conditions after infection, but there have been enlightening developments. 

For example, after analyzing data from 3.9 million patients, a research team from Cleveland, OH, discovered that of the 24 autoimmune diseases studied, 8 showed an increased risk following COVID-19 infection. The highest increases in risk were observed in certain inflammatory and vascular conditions, including cutaneous vasculitis, polyarteritis nodosa, and hypersensitivity angiitis.

Who May Be at Higher Risk?

Not everyone who has COVID-19 develops long-term symptoms, so researchers are working to understand why some individuals are more affected than others.

Potential Risk Factors

Current evidence suggests several possible contributors to the development of long COVID, such as:

• Pre-existing autoimmune conditions
• Severity of the initial infection
• Genetic predisposition to immune dysregulation
• Sex and hormonal factors

Adding to the last bullet point, it is important to remember that autoimmune diseases are generally more common in women. In fact, approximately 78% of people living with autoimmune disease are female.

Vulnerable Populations

Considering the risk factors mentioned above, people with underlying immune system differences or chronic health conditions may be more likely to experience prolonged symptoms.

However, long COVID has also been reported in individuals with mild initial infections, making it difficult to predict who will be affected.

It is important to note that research in this area is still evolving. As more data becomes available, our understanding of risk factors will continue to improve.

Approaches to Managing Symptoms

Managing long COVID and autoimmune disease requires a personalized and flexible approach. While there is no single treatment that works for everyone, the strategies listed in the table below may help support recovery and symptom management.

What to Expect During a Medical Evaluation

A healthcare provider should always evaluate persistent or worsening symptoms. Three goals that will likely serve as the foundation of your medical evaluation are:

1. Assessing for underlying autoimmune conditions
2. Monitoring inflammatory markers
3. Developing an individualized care plan

Building on point #3: Because long COVID presents differently in each patient, every care plan should be tailored to individual needs, symptoms, and health history. Therefore, patients are encouraged to seek providers who take their symptoms seriously and are willing to explore comprehensive approaches to care, well after getting a diagnosis.

What Scientists Are Still Learning

The connection between long COVID and autoimmunity is one of the most actively studied areas in post-pandemic health research. Long COVID is now recognized as a legitimate and complex health condition, which improves both diagnosis and access to care.

Still, researchers continue to investigate things like:

• Whether long COVID is a distinct condition or a group of related syndromes
• The role of autoantibodies and immune dysfunction
• Long-term outcomes and recovery patterns

While many questions remain, the pace of research is encouraging. When it comes to autoimmunity, there are always breakthroughs in research and new therapies on the horizon.

Taking a Proactive Approach to Long-Term Health

For individuals experiencing lingering symptoms after COVID-19, staying informed and proactive is key. Make sure you consistently monitor changes in your health and seek medical evaluation when something feels off. Early recognition of symptoms and appropriate management strategies may reduce long-term impact and improve quality of life.

Your medical provider can help you understand potential connections between long COVID and autoimmune disease. However, each patient should take it upon themself to find additional support. The Autoimmune Association provides educational information, advocacy opportunities, and community resources for individuals navigating autoimmune-related challenges, including those associated with SARS-CoV-2, even though long COVID is not an autoimmune disease per se.

You can stay up to date on all news relating to autoimmune diseases by signing up for the monthly Research Roundup newsletter from the Autoimmune Association.