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New Study By Dr. Akiko Iwasaki Finds That Autoantibodies Can Drive Severe Neurological Symptoms In People with Long Covid

Dr. Akiko Iwasaki is the Sterling Professor of Immunobiology at Yale University; director of the Yale Center for Infection and Immunity; one of Time magazine’s 100 most influential people in the world for 2024; and a powerful champion for patients with Long Covid, ME/CFS, and other infection-associated chronic illnesses (IACIs). Her lab published hundreds of papers, in the best research journals, on how infection-associated chronic conditions and illnesses (IACCIs) affect the immune system. In a just-posted preprint of their most recent work, her team members tested whether autoantibodies in patients with COVID could cause the neurological symptoms of Long Covid.

Infection with the SARS-CoV-2 virus causes some patients to develop autoantibodies—which are antibodies that recognize and damage human tissues, instead of recognizing and destroying foreign pathogens. Usually, autoantibody levels go back down as patients recover from acute infection. But some patients with Long Covid continue to have high autoantibody levels, and patients infected with SARS-CoV-2 have a significantly greater chance of developing multiple new autoimmune diseases than do uninfected people. Interestingly, autoantibody levels are also high in some patients with other IACIs (like ME/CFS or chronic Lyme disease), and both autoimmune diseases and IACCIs affect women more often than men. These facts suggest autoantibodies can cause cases of Long Covid and other IACIs. Autoantibodies in patients with IACCIs can especially interfere with the nervous system; for example, they can bind and disrupt proteins important for brain signaling. In this work, Dr. Iwasaki’s team tested whether autoantibodies caused neurological symptoms of Long Covid in some patients.

The team purified antibodies from patients suffering from intense neurological symptoms of Long Covid, like severe brain fog, headache, memory loss, dizziness, insomnia, and confusion. While none of these patients had autoimmune diseases, the team found the patients had significant levels of autoantibodies, specifically autoantibodies attacking neuronal tissues. Fascinatingly, autoantibodies from patients with distinct symptoms recognized distinct neuronal tissues. For example, patients with headache, poor memory, weakness, and disorientation had autoantibodies against meninges tissues. And to a lesser extent, patients with tinnitus had autoantibodies against sciatic nerve tissue. The team then tested whether distinct autoantibodies could cause distinct symptoms. They injected antibodies from patients with certain symptoms into mice; then, they measured Long Covid–associated symptoms. Mice injected with antibodies from patients with chronic pain or dysautonomia became more sensitive to pain than did mice injected with antibodies from healthy people. And to a lesser extent, mice injected with antibodies from patients with tinnitus became weaker than did mice injected with antibodies from healthy people. Nine in ten mice who became imbalanced and uncoordinated after injection had receiving antibodies from patients with dizziness. Overall, these results showed that autoantibodies from patients with distinct Long Covid symptoms (chronic pain, headache, tinnitus, dizziness, and dysautonomia) caused distinct and parallel symptoms in mice (pain, imbalance, and weakness).

An important conclusion from this work is that autoantibodies can drive severe neurological symptoms in patients with Long Covid. This information is critical because if we know which patients have such autoantibodies, we could treat those patients by neutralizing the autoantibodies. For example, we could treat patients with high autoantibody levels by using intravenous immunoglobulin therapy, BC007 therapy, plasmapheresis, anti-CD20 therapy, or FcRn-inhibitor therapy; and treat patients with low autoantibody levels by using other methods. (Consistent with this is the fact that intravenous immunoglobulin therapy clearly helps some patients with Long Covid, but not all.)

Dr. Iwasaki notes that the key next steps are to understand which neuronal proteins the autoantibodies target and what happens to these neuronal proteins and neuronal tissues when targeted by autoantibodies. Knowing the autoantibody targets and the consequences of targeting would let us better understand how autoantibodies cause neuronal symptoms and better diagnose and treat patients.

Read the preprint here.

Learn about Solve’s recent visit to Dr. Iwasaki’s lab to present Solve Together here.

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