When the Pain Lingers: What COVID-19 Taught Us About Joint Pain, Fatigue, and Autoimmune Risk

More than four years into the pandemic, many people are still trying to figure out why their body never quite felt the same after COVID-19. For some, it’s lingering fatigue. For others, it's brain fog or chest pain. But for a growing number of people, joint pain, stiffness, and full-blown autoimmune symptoms are the long-haul gifts no one asked for.

As a rheumatologist, I’ve been seeing more and more patients who recovered from COVID—only to later develop symptoms that look very much like rheumatoid arthritis (RA), fibromyalgia, or polymyalgia rheumatica (PMR). And emerging research now supports what we’re seeing in the clinic.

How Common Is Post-COVID Joint Pain?

According to a systematic review of 31 studies published in 2022, joint pain affected anywhere from 2% to 65% of patients in the weeks to months after COVID-19 infection. The wide range reflects differences in patient populations, timing, and definitions used across studies—but the trend is real.

Even more concerning, fibromyalgia-like symptoms—including widespread pain, fatigue, and sleep disturbances—were reported in 31% to 40% of patients who had recovered from COVID. For many, these were new symptoms, with no prior history of chronic pain conditions.

COVID-19 and New Autoimmune Diagnoses: Coincidence or Trigger?

Beyond general aches and pains, clinicians are now documenting true autoimmune rheumatic diseases developing for the first time after COVID. These include:

• Rheumatoid Arthritis (RA)

• Polymyalgia Rheumatica (PMR)

• Reactive Arthritis

• Psoriatic Arthritis

• Systemic Lupus Erythematosus (SLE) (less frequently)

Many of these patients test positive for autoantibodies, such as rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP or ACPA) antibodies. These markers are not just incidental lab findings—they’re core diagnostic criteria for diseases like RA.

What Are Anti-CCP (ACPA) Antibodies, and Why Do They Matter Post-COVID?

Anti-CCP antibodies (also known as ACPA) are highly specific for rheumatoid arthritis. People who test positive for anti-CCP are more likely to:

• Develop more aggressive forms of RA

• Have joint erosions earlier in the disease

• Experience longer disease duration and higher disability if untreated

In the systematic review, several case reports and cohort studies identified new-onset RA with elevated anti-CCP levels following COVID-19. One patient, for example, developed polyarthritis three weeks after infection and tested positive for both RF and anti-CCP, prompting a formal RA diagnosis.

Other patients had low or borderline anti-CCP titers, raising concern about early or evolving autoimmune activation. While these antibodies alone don't confirm disease, their presence—especially when paired with clinical symptoms—should not be ignored.

Why Is This Happening? The Immune System’s Overreaction

The connection between viral infections and the triggering of autoimmune diseases is well-established. Likewise, the immune and inflammatory responses elicited by viral infections have been extensively studied. In fact, before HIV was formally identified and named, some researchers referred to it as a “systemic immune dysregulation syndrome” or used similar terminology to describe the profound immune abnormalities it caused. Additionally, Epstein-Barr Virus (EBV) is strongly implicated as a potential environmental trigger in the development of autoimmune diseases, particularly systemic lupus erythematosus (SLE).

We’re still uncovering the exact mechanisms, but researchers believe COVID-19 can act as an autoimmune trigger via several immune pathways:

• Molecular Mimicry: Parts of the SARS-CoV-2 virus may resemble human proteins, leading to cross-reactive immune responses.

• Bystander Activation: Tissue damage during COVID-19 may release self-antigens, which are mistakenly targeted by immune cells.

• Epitope Spreading: As inflammation spreads, new self-proteins become immune targets, worsening the autoimmune cascade.

• Hyperinflammation: Severe COVID-19 can push the immune system into cytokine storm territory, where immune regulation breaks down entirely.

Some studies found RF and anti-CCP levels peaking months after COVID-19, suggesting the virus can set off a delayed autoimmune response that only becomes clinically apparent later.

Treatment: What Can Be Done If You’re Still in Pain?

There’s no universal treatment protocol for post-COVID musculoskeletal symptoms, but options include:

• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for general joint and muscle pain

• Corticosteroids for moderate to severe inflammation

• Physical therapy and guided rehabilitation

• Biologic medications, like TNF or IL-6 inhibitors, if a true autoimmune disease is diagnosed

However, the evidence base is limited, and treatment must be individualized.

How Do We Know This Isn’t Just “Long COVID” Fatigue?

That’s a great question—and one that rheumatologists and researchers are still trying to answer.

A separate study from the Netherlands followed patients with pre-existing inflammatory arthritis and found that 21% developed persistent post-COVID symptoms, compared to 13% of healthy controls. The catch? Many symptoms—like fatigue, joint pain, and brain fog—overlap with their baseline disease, making diagnosis tricky.

The researchers caution that the World Health Organization’s criteria for post-COVID condition may overestimate prevalence in patients with autoimmune diseases, because many of the symptoms were already part of their daily lives.

What Should You Do If You're Experiencing Post-COVID Pain?

If you’re still feeling unwell weeks or months after COVID-19—especially with joint pain, fatigue, or swelling—you may benefit from a rheumatologic evaluation.

Autoantibodies like RF or anti-CCP can offer clues, but the whole clinical picture matters most. A thorough evaluation can distinguish between viral aftereffects and emerging autoimmune disease—and early treatment can make a big difference in outcomes.

Bottom Line

COVID-19 isn’t just a lung infection—it’s a multi-system disease that can tip the immune system into long-term imbalance. Whether it’s triggering entirely new autoimmune diseases or exacerbating existing ones, the impact on joints and muscles is now well-documented and deserves more attention.

If your body hasn’t felt the same since COVID, you’re not alone—and it’s not all in your head. Let’s keep asking questions and supporting research. 

References

1. Ursini, T. et al. Post-acute COVID-19 joint pain and new onset of rheumatic musculoskeletal diseases: a systematic review. Clin Rheumatol. 2022.

2. Boekel, L. et al. Post-COVID condition in patients with inflammatory rheumatic diseases: a prospective cohort study in the Netherlands. Lancet Rheumatol. 2023.

3. Yazdanpanah, N. et al. Autoantibodies in COVID-19: Frequency, association with severity, and prognostic implications. Front Immunol. 2022.

4. Ehrenfeld, M. et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020.

5. World Health Organization. A clinical case definition of post COVID-19 condition by a Delphi consensus. WHO, 2021.

6. Alunno, A. et al. New-onset rheumatic musculoskeletal diseases following SARS-CoV-2 infection: Systematic literature review. Semin Arthritis Rheum. 2022.