Summary: New research identifies autoimmunity as the main biological driver of the puzzling and often disabling symptoms experienced by a distinct subgroup of people with long COVID. Investigators established a direct causal link by isolating antibodies from the blood of long COVID patients and transferring them into healthy mice, producing clear physical and physiological effects in the animals.
This neuro-immune validation supports the use of targeted, already-approved autoimmune treatments—such as intravenous immunoglobulin (IVIG), FcRn inhibitors, plasmapheresis, and advanced CAR-T cell strategies—to reduce chronic symptoms for many affected individuals.
Key Facts
- The long COVID burden: Studies estimate that roughly 4% to 20% of people infected with SARS-CoV-2 develop long COVID, with persistent fatigue, cognitive dysfunction (“brain fog”), heart palpitations, and severe joint and muscle pain lasting months or years. Proposed mechanisms include viral persistence, reactivation of latent viruses (for example, herpesviruses), and immune dysregulation that prevents the immune system from resetting after the acute infection, producing ongoing inflammation.
- Human-to-mouse transfer proof: To isolate the immune system’s role, researchers purified antibodies from the blood of 87 people diagnosed with long COVID and infused those antibodies into healthy laboratory mice. The animals developed marked biological and behavioral changes, demonstrating that circulating autoantibodies can drive physical symptoms associated with long COVID.
- A quantifiable biomarker for therapy selection: Before this study, clinicians lacked a reliable way to predict which patients would benefit from immunomodulatory therapies. The presence of circulating autoantibodies now serves as a measurable marker to identify patients most likely to respond to antibody-lowering or immune-targeted treatments.
- Repurposing existing autoimmune treatments: Validating an autoimmune mechanism justifies the use of established immune-regulating therapies in appropriate patients. Options include IVIG to modulate immune responses, FcRn inhibitors to reduce total antibody levels, plasmapheresis to remove pathogenic antibodies from the blood, and CAR-T cell approaches designed to eliminate cells producing harmful autoantibodies.
- Explaining inconsistent trial results: Past clinical trials for IVIG and similar agents produced mixed outcomes—some long COVID patients recovered dramatically while others experienced no benefit. This study clarifies why: such therapies are effective primarily in the autoimmune subtype of long COVID, so trials that did not stratify participants by autoantibody status produced inconsistent results.
- Public health implications for blood donation: Senior author Dr. David Putrino warns that blood and plasma safety policies may need revision. The United Kingdom excludes people with long COVID from blood donation, while the United States currently allows donations from these individuals. Given that long COVID plasma can contain active autoantibodies, this poses a potential risk to recipients and may require changes to donation guidelines.
Source: Mount Sinai Hospital
A Mount Sinai-led team has shown that autoimmunity—when the immune system attacks the body’s own tissues—explains the confusing and disabling symptoms suffered by a subgroup of people with long COVID.
The study, published in Cell on May 28, validates an autoimmune contribution and points to practical clinical strategies: existing immune therapies can be repurposed, and clinicians can use autoantibody testing to identify patients who are most likely to benefit from these interventions.
“We’ve known for some time that long COVID is not a single condition but a constellation of different phenotypes, and now we have validated that autoimmunity is a major contributor to the symptom burden,” says David Putrino, PhD, Nash Family Director of the Cohen Center for Recovery From Complex Chronic Illness at Mount Sinai and co-senior author of the study. “This new understanding of long COVID physiology will enable us to identify effective autoimmune therapies that could significantly improve symptoms for millions of people.”
Long COVID affects many patients with persistent fatigue, cognitive impairment, palpitations, and musculoskeletal pain. While several biological processes likely contribute, the new findings isolate circulating autoantibodies as a direct cause of physical symptoms in a defined subgroup of patients.
In the key experiments, researchers collected blood from 87 people with long COVID, purified the antibodies, and transferred them into healthy mice. The recipient animals displayed measurable physical and physiological changes, supporting a causal role for autoantibodies. This experimental design provides a stronger level of evidence than observational studies alone.
Clinicians are already using IVIG and FcRn inhibitors for some long COVID patients, but results have been uneven. The study explains that variability: autoimmune-directed therapies work when autoantibodies drive symptoms but not when other mechanisms—such as viral persistence—are dominant. By using autoantibody presence as a screening tool, physicians can run more precise, targeted clinical trials and provide therapies to those most likely to benefit.
Other potential approaches highlighted by the study include plasmapheresis, which physically removes pathogenic antibodies from circulation, and CAR-T cell strategies that could be engineered to target the cells producing harmful autoantibodies. These options expand the therapeutic toolbox for the autoimmune subtype of long COVID.
Dr. Putrino also voices an urgent policy concern: the potential risk posed by blood and plasma donations from people with long COVID. “In the U.K., long COVID is an exclusion for blood donation, while in the U.S. it is not,” he notes. “Because our findings show long COVID plasma can carry active autoantibodies that may endanger recipients, U.S. donation policies should be reconsidered to fully protect public health.”
Key Questions Answered:
A: By transferring purified antibodies from 87 long COVID patients into healthy mice and observing clear biological effects in the animals, researchers demonstrated that circulating autoantibodies can directly cause long-term physical symptoms.
A: Long COVID comprises multiple biological subtypes. IVIG and FcRn inhibitors target autoimmune mechanisms, so they are effective when autoantibodies drive the disease but not when other processes—such as persistent viral infection—are the cause. Without stratifying patients by autoantibody status, trial results will appear inconsistent.
A: The study highlights a policy gap: the U.K. excludes people with long COVID from donating blood, while the U.S. does not. Because plasma from people with long COVID can contain harmful autoantibodies, the authors recommend revisiting U.S. donation guidelines to protect recipients.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by editorial staff.
About this long COVID research news
Author: Ilana Nikravesh, Mount Sinai Hospital
Source: Mount Sinai Hospital
Contact: Ilana Nikravesh – Mount Sinai Hospital
Image: Image credited to Neuroscience News
Original Research: Findings published in Cell.