What is Long COVID and why should people with autoimmune or chronic illness be concerned?

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is a complex condition where symptoms persist or emerge after a COVID-19 infection. People with autoimmune disease, chronic illness, or who are immunocompromised may face unique risks from COVID-19 itself and may experience more severe or prolonged symptoms if they develop Long COVID.

Are people with autoimmune diseases or weakened immune systems at higher risk for Long COVID?

Emerging research suggests that individuals with autoimmune disease or who are immunocompromised may have distinct vulnerabilities. Factors such as immune system dysregulation, severity of initial infection, and lower vaccine response may contribute to a higher risk of Long COVID in these populations, though the exact degree of risk is still under investigation.

Can Long COVID trigger autoimmune diseases or worsen existing ones?

Yes. Long COVID may unmask, trigger, or worsen autoimmune conditions. Some individuals develop new autoimmune diseases following COVID-19, while others experience flare-ups of preexisting autoimmune symptoms. This may be due to lingering immune activation, viral persistence, or reactivation of latent viruses.

What are the most common Long COVID symptoms?

While Long COVID symptoms vary widely, individuals with underlying conditions often report:

• Increased fatigue and post-exertional malaise
• Brain fog and memory issues
• Muscle and joint pain
• Shortness of breath and chest discomfort
• Autonomic symptoms such as dizziness, palpitations, or POTS-like episodes
• Gastrointestinal problems

These symptoms may overlap with existing illness, making it difficult to distinguish Long COVID flares from baseline disease activity.

Is Long COVID considered an autoimmune disease?

Long COVID is not formally classified as an autoimmune disease. However, growing evidence suggests it may involve autoimmune-like processes in some patients, including the presence of autoantibodies and prolonged immune activation. It may also trigger autoimmune disease in people with genetic or environmental susceptibility.

Is there a diagnostic test for Long COVID?

The short answer is that, while promising research is underway, a definitive diagnostic test for Long COVID has not been established as of March 2025.

Ongoing research is exploring potential biomarkers that could aid in diagnosis. For instance, a study reported by Medscape in November 2023 identified certain immune system proteins that, when elevated, might predict the presence of Long COVID with approximately 78.5% accuracy. Despite these advancements, such tests are still under investigation and are not yet part of standard diagnostic protocols.

In clinical practice, healthcare providers may use various tests to assess and manage symptoms associated with Long COVID, such as blood tests, imaging studies, and pulmonary function tests. These are primarily employed to rule out other conditions and to guide treatment rather than to confirm a Long COVID diagnosis.

How is Long COVID diagnosed in someone with an existing chronic illness?

Diagnosis is clinical and based on a history of COVID-19 infection followed by new or worsening symptoms not explained by another condition. For individuals already living with autoimmune or chronic diseases, diagnosis may require tracking symptom changes and excluding other causes.

What treatments are available—and are they safe for people with immune system concerns?

There is no FDA-approved treatment specifically for Long COVID, but many people benefit from symptom-based care. Treatment strategies may include:

• Energy conservation and pacing strategies (especially for fatigue and post-exertional malaise)
• Physical or pulmonary rehabilitation
• Cognitive rehabilitation for brain fog
• Medications for specific symptoms (e.g., sleep, pain, heart rate)
• Nutritional support and mental health care

People who are immunocompromised or on immunosuppressive medications should discuss the risks and benefits of any new treatments with their healthcare providers.

What research is being done to better understand Long COVID in immunocompromised and chronically ill populations?

The NIH’s RECOVER Initiative is the largest U.S. research effort on Long COVID. The RECOVER clinical trials team is partnering with patient and community representatives, including through NIH CEAL, as well as the RECOVER National Community Engagement Group to reach communities of people who have historically been underrepresented in research. In addition, a track record for enrolling diverse participants is a key criterion for trial site selection. Each trial is designed to test multiple treatments at once, improving the speed at which potentially helpful interventions can be identified and advanced.

RECOVER includes clinical trials focused on symptoms common among people with chronic illness, such as:

RECOVER-VITAL

Evaluates therapies targeting viral persistence, one potential root cause of Long COVID. Paxlovid (nirmatrelvir/ritonavir) is among the treatments under investigation.

RECOVER-NEURO

Tests interventions for brain fog and neurocognitive dysfunction, a common and debilitating symptom.

RECOVER-AUTONOMIC

Focuses on treatments for autonomic dysfunction, including conditions like postural orthostatic tachycardia syndrome (POTS).

RECOVER-SLEEP

Addresses long-term sleep disturbances reported by many people with Long COVID.

RECOVER-ENERGIZE

Investigates therapies for fatigue, exercise intolerance, and post-exertional malaise—symptoms that also overlap with ME/CFS.

Is the NIH’s RECOVER Initiative at risk of being shut down?

​As of March 26, 2025, the closure of the federal Office of Long COVID Research and Practice does not appear to directly impact the National Institutes of Health’s (NIH) RECOVER Initiative. The RECOVER Initiative operates under the NIH’s purview and has received substantial funding allocations, including an additional $515 million in February 2024 and $147 million in reallocated funds in December 2024, to support its ongoing research efforts. 

However, it’s important to note that the broader reorganization within the Department of Health and Human Services (HHS) has led to significant funding withdrawals from various COVID-19-related programs. For instance, the Trump administration announced the rescinding of $11.4 billion in COVID-19-related funds from state and local health departments and other health organizations.  While the RECOVER Initiative has not been specifically mentioned in these funding retractions, the overall shift in federal priorities may influence future support for Long COVID research.​

Therefore, while the RECOVER Initiative remains operational and funded at this time, the evolving landscape of federal health priorities suggests that continued vigilance is necessary to ensure sustained support for Long COVID research initiatives.

What is happening with the federal Office of Long COVID Research and Practice?

The Office of Long COVID Research and Practice, launched by the U.S. Department of Health and Human Services in August 2023, was designed to coordinate a whole-of-government response to the long-term effects of COVID-19. However, as of early 2025, internal communications and independent reporting suggest the office is being phased out. While no formal announcement has been made, the office is expected to shut down as part of a broader reorganization, raising concerns about the loss of centralized leadership, research momentum, and federal commitment to Long COVID care and coordination.

Can vaccines help protect against Long COVID for immunocompromised or chronically ill individuals?

COVID-19 vaccines are associated with a reduced risk of developing Long COVID in many studies, but the degree of protection varies by individual and variant. For people who are immunocompromised or living with autoimmune disease, the immune response to vaccination may be less robust. Vaccination remains an important tool, especially when combined with early treatment and continued risk mitigation.

How can people with autoimmune or chronic illness tell the difference between Long COVID and a flare?

It can be challenging. People living with chronic illness may already experience symptoms such as fatigue, brain fog, or joint pain. Key indicators of Long COVID include the emergence of new symptoms, a notable shift in baseline function, or increased symptom severity following COVID-19. Keeping a symptom journal and working with healthcare providers can help clarify what’s new.

Where can I find support and information specific to Long COVID and chronic illness?

Many hospitals now offer multidisciplinary post-COVID care clinics. National and local support groups, condition-specific nonprofits, and online patient communities may provide education, advocacy, and peer support. Look for providers familiar with complex chronic illness and post-viral recovery.