Santos Guedes de Sá et al. (2024)
- Authors: Keyla Santos Guedes de Sá, Julio Silva, Rafael Bayarri-Olmos, Ryan Brinda, Robert Alec Rath Constable, Patricia A. Colom Diaz, Dong-il Kwon, Gisele Rodrigues, Li Wenxue, Christopher Baker, Bornali Bhattacharjee, Jamie Wood, Laura Tabacof, Yansheng Liu, David Putrino, Tamas L. Horvath, Akiko Iwasaki
- Institutes: Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA, Center for Infection and Immunity, Yale School of Medicine, New Haven, CT, USA, Nash Family Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Publisher: medRxiv
- Link: DOI
Summary
This landmark study provides some of the most compelling evidence to date that Long COVID symptoms can be caused by the body’s own immune system attacking the nervous system. By demonstrating that symptoms can be transferred from humans to animals via antibodies, it transforms our understanding of the disease from a collection of vague symptoms to a measurable autoimmune condition. This discovery offers immediate hope for the use of existing immunotherapies in a specific subset of patients.
What was researched?
This study investigated whether autoantibodies found in Long COVID patients are directly responsible for neurological and neurocognitive symptoms.
Why was it researched?
Although previous research found elevated autoantibodies after SARS-CoV-2 infection, it was unclear if these were merely bystanders or the actual cause of persistent symptoms like brain fog and pain.
How was it researched?
Scientists used a human protein array to identify autoantibody targets in patients and then transferred purified Immunoglobulin G (IgG) from these patients into mice. They then monitored the mice for behavioral and physiological changes mirroring the human symptoms.
What has been found?
Patient IgG reacted with human brainstem tissue and mouse peripheral nerves, and mice receiving these antibodies developed increased pain sensitivity, loss of coordination, and small fiber neuropathy. These findings demonstrate that the autoantibodies are functional and capable of inducing disease.
Discussion
While the study provides a strong mechanistic link, the wide variety of autoantibodies found suggests significant patient heterogeneity. The use of mouse models is a strength but also a limitation in capturing the full human experience of Long COVID.
Conclusion & Future Work
The results suggest that a subset of Long COVID is a bone fide autoimmune disease. This paves the way for clinical trials using treatments like intravenous immunoglobulin (IVIG) 💊 or plasmapheresis to remove or neutralize these harmful antibodies.