Presenting Author: Keyla S G Sa
, Postdoctoral Associate at Yale Univ.
Abstract:
We and others have shown that SARS-CoV-2 infection triggers the generation of diverse and autoantibodies (AAB) targeting the extracellular proteome in patients who had both severe and mild acute COVID-19. A sex-desegregated analysis of AAB reactivities using REAP data revealed that females with Long COVID demonstrated a higher number of REAP hits. At the time of enrollment, these individuals reported not having an autoimmune diagnosis. We observed that purified IgG from Long Covid patients showed reactivity against mouse sciatic nerves, spinal cord, and human pons, which strongly suggests the presence of AABs targeting both the central nervous system (CNS) and the peripheral nervous system (PNS). After passive transfer of human IgG to mice, we observed that 5% of the IgG crosses the blood-brain barrier and mice displayed loss of balance and coordination, reduction of muscle strength, and increased sensitivity to thermal pain with small fiber nerve damage. These phenotypes are consistent with the participants’ reported symptoms, such as confusion, dizziness, disorientation, weakness, and fatigue, and with the staining pattern that we observe in the spinal cord and sciatic nerve as well as with the functions associated with the top candidate proteins targets identified by REAP. These results demonstrate the sufficiency of AAB from patients with long COVID to induce various neurological symptoms in mice and suggest a possible therapeutic target for those with similar AAB.
Autoantibodies from Long COVID patients trigger CNS and PNS symptoms in mice
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1