How Immune System Attacks Contribute to Prolonged Coronavirus Infections

Emerging research indicates that prolonged COVID-19 infections may stem from the immune system attacking healthy tissue. Insights from four recent studies highlight autoimmunity as a potential contributor, especially in cases where intense pain is a prominent symptom.

This revelation could pave the way for urgently needed treatments, currently non-existent in the UK and US. “We must explore removing antibodies from patients to see if symptoms abate,” asserts Niels Eikelkamp from Utrecht University, Netherlands.

<p>While most individuals infected with SARS-CoV-2 recover swiftly, a subset experiences prolonged symptoms lasting months or years. Common complaints include fatigue, chronic pain, brain fog, and excessive tiredness following minimal exertion.</p>
<p>Researchers have pinpointed various potential mechanisms behind long COVID, such as persistent SARS-CoV-2 presence and gut microbiome dysfunction. These factors may be involved in diverse combinations within individuals, complicating the search for effective universal treatments.</p>
<p>A frequently discussed mechanism is autoimmunity, in which the immune system mistakenly targets the body. Typically, antibodies are designed to eliminate pathogens; however, autoantibodies can erroneously attach to the body’s own cells.</p>
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<p>Initial indications of autoantibodies playing a role in prolonged COVID-19 cases emerged from studies conducted in 2023. Apheresis treatments on individuals with long-term coronavirus infection showed reductions in autoantibody levels and improvements in symptoms, yet the exact substances responsible remain undetermined due to the broad spectrum of removals.</p>
<p>Eikelkamp and his team now provide robust evidence that autoantibodies can prolong COVID-19 symptoms. Their 2022 study involved 34 participants experiencing long COVID, and 15 who had recovered. The focus was on immunoglobulin G (IgG) antibodies, which were administered to mice.</p>

<p>Mice injected with IgG from long COVID patients displayed heightened sensitivity to touch and pain, removing their paws from hot surfaces more quickly than those who received antibodies from non-long COVID participants. Eikelkamp noted that this aligns with symptoms reported by long COVID patients.</p>
<p>In 2024, the team repeated the experiment with IgG from 19 long COVID patients, confirming similar results. "These autoantibodies persist in the patient’s body," comments <a href="https://www.unamur.be/en/profil/nicaisec">Charles Nicaise</a>, who participated in another study from the University of Namur, Belgium.</p>
<p>This aligns with findings from three other preliminary studies. One led by <a href="https://medicine.yale.edu/profile/akiko-iwasaki/">Akiko Iwasaki</a> at Yale University found elevated autoantibody levels in patients with both long COVID and neurological symptoms. Mice injected with these antibodies also exhibited similar pain and balance issues.</p>
<p>The two remaining studies, published in November 2025, found that mice injected with IgG from long COVID patients demonstrated decreased skin nerve fiber density, indicating nerve damage, and heightened sensitivity to cold and touch.</p>

<p>Ongoing research by Nicaise's team has found that IgG from long COVID patients leads to increased pain sensitivity in mice, with IgG accumulating around neurons involved in relaying sensory information, especially pain.</p>
<p>To transform these findings into effective treatments, it's crucial to identify which specific types of IgG are implicated in symptoms. Iwasaki's experiments have spotlighted two particular target proteins, MED20 and USP5.</p>
<p>Furthermore, it's essential to assess whether removing or inhibiting the activity of these autoantibodies alleviates symptoms. <a href="https://www.amsterdamumc.org/en/research/researchers/brent-appelman">Brent Appelman</a> from Eikelkamp’s team studies the effects of filtering these autoantibodies from patients' blood. While Eikelkamp acknowledges that apheresis isn’t a permanent solution—requiring hospital visits every few months—he views it as a promising proof of concept paving the way for more advanced medical therapies.</p>

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