Summary: New research from Mount Sinai indicates that autoimmunity is the main biological driver of debilitating long COVID symptoms for a defined subset of patients. Investigators demonstrated a direct causal relationship by isolating antibodies from people with long COVID and transferring them into healthy mice, which then developed measurable physical and physiological changes consistent with the human condition.
This neuro-immune validation supports the targeted use of existing autoimmune therapies—such as IVIG, FcRn inhibitors, plasmapheresis, and advanced CAR-T cell approaches—to reduce chronic symptoms for many affected individuals.
Key Facts
- Prevalence and symptoms: Between 4% and 20% of people infected with SARS-CoV-2 develop long COVID, experiencing persistent fatigue, cognitive impairment (“brain fog”), heart palpitations, and chronic joint and muscle pain that can last months or years. Contributing mechanisms include viral persistence, reactivation of latent viruses (for example, herpesviruses), and immune dysregulation that keeps the body in a state of chronic inflammation.
- Human-to-mouse transfer proof: To isolate the role of the immune system, researchers purified antibodies from 87 people diagnosed with long COVID and infused those antibodies into healthy laboratory mice. The animals developed striking biological changes, providing clear evidence that circulating autoantibodies can drive long COVID symptoms.
- Predictive biomarker: The presence of circulating autoantibodies now emerges as a quantifiable biomarker that can identify patients most likely to benefit from antibody-lowering or immune-modulating therapies, enabling a precision-medicine approach.
- Repurposing autoimmune treatments: With autoimmune physiology validated in this subgroup, clinicians can more confidently consider established treatments: Intravenous Immunoglobulin (IVIG) to rebalance immune responses, FcRn inhibitors to reduce antibody levels, plasmapheresis to remove pathogenic antibodies directly, and CAR-T strategies to target cells producing harmful autoantibodies.
- Resolving inconsistent trial results: Prior clinical trials of immune therapies for long COVID produced mixed outcomes. This study explains that discrepancy: therapies that target autoimmunity will only help patients whose symptoms are driven by autoantibodies, not those with other underlying mechanisms.
- Blood safety concerns: The study raises a public health issue about blood and plasma donation. While the United Kingdom excludes people with long COVID from donating blood, the United States currently allows donations from these individuals. The authors warn this policy gap could pose risks for transfusion recipients and argue for policy review.
Source: Mount Sinai Hospital
Overview: A research team led by Mount Sinai has shown that autoimmunity—in which the immune system mistakenly attacks the body’s own tissues—accounts for the confounding and often-debilitating symptoms of long COVID in a distinct subset of patients. Their findings were published in Cell on May 28 and point to practical ways to identify and treat patients whose condition is driven by autoantibodies.
“Long COVID includes multiple biological phenotypes, and our study validates that autoimmunity is a major contributor to symptom burden for a subset of patients,” said 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 paper. “Recognizing this physiology allows clinicians to select effective, already-available treatments that may significantly reduce symptoms for millions of people.”
The research team focused on immune mechanisms by extracting and purifying antibodies from the blood of 87 participants with long COVID and transferring those antibodies into healthy mice. The animals developed measurable changes that mirror elements of the human syndrome, providing proof that these autoantibodies are sufficient to produce long-term physical effects.
Clinically, these results offer a method to stratify patients for therapy. Intravenous immunoglobulin (IVIG)—pooled antibodies from healthy donors—can modulate or normalize immune responses and is already used in autoimmune disorders. FcRn inhibitors reduce the concentration of circulating antibodies and are another existing class of biologics. Both IVIG and FcRn inhibitors have been tried in people with long COVID with variable outcomes; this study explains that variability by showing that only patients with detectable autoantibodies are likely to benefit.
Beyond those options, the study highlights other targeted strategies under consideration. Plasmapheresis can physically remove pathogenic antibodies from the bloodstream, and CAR-T cell therapy could, in principle, be engineered to eliminate the cells producing harmful autoantibodies. These approaches remain complex and require rigorous clinical evaluation, but the new biological insight strengthens the rationale for such trials.
“Until now, clinicians lacked a reliable way to predict who would respond to therapies like IVIG or FcRn inhibitors,” Putrino explained. “Our findings indicate that circulating autoantibodies are a measurable marker to identify candidates for these treatments, enabling precision-targeted clinical trials.”
The team also warned of an urgent public health implication: plasma and blood donations from people with long COVID could contain harmful autoantibodies. “The U.K. excludes people with long COVID from blood donation, but the U.S. still allows it. Given the potential danger to recipients, U.S. donation policies should be re-evaluated to better protect public health,” Putrino said.
Key Questions Answered:
A: Researchers purified antibodies from 87 people with long COVID and injected them into healthy mice. The mice developed clear biological and physical changes, demonstrating that these autoantibodies can directly cause long-term symptoms.
A: Long COVID comprises several distinct biological subtypes. IVIG and FcRn inhibitors target autoimmune mechanisms, so they are effective only when a patient’s symptoms are driven by autoantibodies. If symptoms stem from other causes—such as persistent viral reservoirs—those therapies are unlikely to help.
A: The study highlights a potential safety gap: plasma from people with long COVID can contain active autoantibodies that may harm recipients. The authors note that the U.K. excludes long COVID patients from donating blood, whereas the U.S. does not, and they call for a review of donation policies to protect public health.
Editorial Notes:
- Article edited by a Neuroscience News editor.
- Journal paper reviewed in full by editors.
- Additional context added by editorial staff to clarify clinical implications.
About this long COVID research news
Author: Ilana Nikravesh
Source: Mount Sinai Hospital
Contact: Ilana Nikravesh – Mount Sinai Hospital
Image: The image is credited to Neuroscience News
Original Research: Findings published in Cell (May 28).