Summary: New findings reveal autoimmunity is the primary biological driver behind the confounding and often-debilitating symptoms of long COVID in a distinct subset of patients. The study demonstrated a direct causal link by purifying antibodies from the blood of human long COVID patients and infusing them into healthy mice, yielding striking physical and physiological results.
This major neuro-immune validation opens the door to using targeted, already-validated autoimmune therapies, such as IVIG, FcRn inhibitors, plasmapheresis, and advanced CAR-T cell therapy, to systematically reduce the chronic symptom burden for millions of individuals.
Key Facts
- The Long COVID Burden: Between 4% and 20% of individuals infected with COVID-19 go on to develop long COVID, enduring persistent fatigue, cognitive impairment (“brain fog”), heart palpitations, and severe joint and muscle pain for months or years. The underlying pathology involves viral persistence, latent virus reactivation (such as herpesviruses), and a damaged, un-reset immune system trapped in chronic inflammation.
- The Human-to-Mouse Transfer Proof: To isolate the exact role of the immune system, researchers collected and purified antibodies from the blood of 87 human participants diagnosed with long COVID and infused them directly into healthy laboratory mice, establishing an unmistakable biological trigger for the condition’s physical symptoms.
- A Quantifiable Screening Tool: Prior to this study, clinicians had no way of predicting which long COVID patients would respond to specialized immunotherapies. The findings prove that the presence of circulating autoantibodies acts as a clear, quantifiable biomarker indicating which patients are optimal candidates for antibody-lowering drugs.
- Repurposing the Autoimmune Arsenal: Validating this autoimmune physiology allows scientists to confidently deploy existing, highly sophisticated immune-regulating treatments. These include Intravenous Immunoglobulin (IVIG) to balance the immune response, FcRn inhibitors to lower overall antibody counts, Plasmapheresis to physically filter autoantibodies out of the blood, and CAR-T cell therapy to genetically program a patient’s T cells to hunt down and destroy the cells secreting harmful autoantibodies.
- Overcoming Industry Hesitancy: Clinical trials for treatments like IVIG have previously yielded highly inconsistent real-world results, with some long COVID patients recovering completely while others saw no change, which severely dampened pharmaceutical industry enthusiasm. This study resolves the mystery: the drugs only work if the patient belongs to the specific autoimmune subtype, allowing for precision-targeted clinical trials.
- An Urgent Public Health Warning: Senior author Dr. David Putrino issues a stark warning regarding global blood supply safety. While individuals with long COVID are strictly excluded from donating blood in the United Kingdom, the United States still permits them to donate, posing a hidden public health threat to blood and plasma recipients that demands immediate policy updates.
Source: Mount Sinai Hospital
A Mount Sinai-led research team has demonstrated that autoimmunity, where the body’s immune system attacks its own tissues, is responsible for the often-debilitating and confounding symptoms of long COVID in a subset of people.
Findings from the study, published in Cell on May 28, could lead to important new approaches to treating patients with long COVID, including already-validated therapies for management of autoimmunity as well as new ways of clinically identifying which patients are most likely to benefit from these therapies.
“We’ve known for some time that long COVID involves not just one but a variety of 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 awareness of the physiology of long COVID will enable us to identify a number of effective treatments for autoimmunity that could significantly improve the symptoms of millions of people with this chronic condition.”
Studies have shown that between 4 and 20 percent of people infected with COVID-19 continue to experience symptoms such as persistent fatigue, cognitive impairment, heart palpitations, and joint and muscle pain for months or even years. Mechanisms behind this prolonged form of the disease are believed to include viral persistence, reactivation of previously latent viruses such as herpesviruses, and immune dysregulation, where the immune system struggles to reset after the infection has cleared, leading to ongoing inflammation and other health issues.
In this new study, researchers sought to better understand the different subtypes of long COVID and the involvement of the immune system in triggering long-term physical symptoms. To that end, researchers collected and purified antibodies from the blood of 87 participants with long COVID and infused them into healthy mice. The results were striking.
Moreover, that awareness could inform which therapies are most likely to reduce the symptom burden. Intravenous immunoglobulin (IVIG), for example, contains antibodies from healthy human donors that are commonly used to treat autoimmune disorders like lupus by strengthening or regulating the recipient’s immune system. FcRn inhibitors are other biologic agents that could help long COVID patients by lowering the amount of antibodies. IVIG and FcRn inhibitors are already being prescribed for some patients with long COVID, though the outcomes have been inconsistent, with some patients responding exceedingly well while others do not. That, in turn, has served to dampen enthusiasm within the industry for long COVID research.
Also on the radar screen of scientists as they investigate new and repurposed therapies for long COVID, according to Dr. Putrino, are CAR-T cell therapy, with the potential to genetically modify a person’s T cells to recognize and target harmful cells secreting autoantibodies, and plasmapheresis, which could simply remove those autoantibodies from the system.
“Before we had no way of predicting who would benefit from therapies like IVIG or FcRn inhibitors,” he says. “Our study now shows that if you are in a subgroup of long COVID patients who have autoantibodies circulating in your body, this is a quantifiable sign that you may be a good candidate for these drugs.”
In addition to its clinical significance, Dr. Putrino believes his study carries an urgent public health warning around the donation of blood and blood products like plasma. He explains: “In the U.K., having long COVID is an exclusion for donating blood, while in the United States these individuals are still allowed to donate. Given the dangers that plasma from people with long COVID can pose for others, this country should be considering fundamental changes to its donation policies that reflect that health threat and are designed to fully protect the public.”
Key Questions Answered:
A: They proved it by transferring the physical disease from humans to animals. The Mount Sinai-led research team extracted and purified antibodies from the blood of 87 long COVID patients and injected them into healthy mice. The resulting striking biological changes in the mice proved that these rogue “autoantibodies” are directly responsible for causing the long-term physical symptoms.
A: Because long COVID is a complex condition made up of several completely different biological subtypes. IVIG and FcRn inhibitors are designed specifically to target and regulate autoimmune disorders. If a patient’s long COVID is driven by a different subtype, like a lingering hidden virus, these drugs won’t work, which is why previous clinical trials showed confusing, inconsistent results that frustrated the medical industry.
A: It exposes a massive blind spot in American public health policy. Currently, the UK completely bans long COVID patients from donating blood to protect the public, but the US still allows it. Because this study proves that long COVID plasma contains active, harmful autoantibodies that can potentially endanger a recipient, Dr. David Putrino is calling for immediate, fundamental changes to US blood donation guidelines.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
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: The findings will appear in Cell
