IgA Autoimmunity and Thrombosis among PASC Patients with Persistent Respiratory Symptoms

Introduction: We previously observed that in respiratory-post-acute sequelae of SARS-CoV-2 (PASC) patients, the levels of autoimmune IgA in plasma are strongly correlated with clotting parameters such as fibrinogen levels and fibrin-related clot strength. Therefore, we intend to study the relation between autoimmunity and thrombosis in PASC patients to determine whether these antibodies induce micro-coagulation in PASC patients that causes the observed respiratory symptoms.

Objective: Our study intends to identify a causal relation between autoimmunity (IgA circulating antibodies) and coagulation in PASC patients.

Methods: We will use plasma and PBMC samples from PASC patients and controls to determine their levels of total and autoimmune circulating antibodies using specific ELISAs, as well as the levels of circulating B-cell secreting those antibodies by ELISPOT. We will also determine coagulatory parameters and markers of vascular injury and NETosis by ELISA. We also intend to characterize the autoimmune antibody-secreting B-cell transcriptomic profile of respiratory-PASC patients by single-cell transcriptomics (scRNAseq) to identify the subpopulations of B-cells that are involved in PASC autoimmunity. Functional assays will be performed using in vitro clotting to characterize the pro-thrombotic activity autoimmune antibodies and endothelial activation assays to determine their role in vascular disfunction.

Results: Preliminary findings indicate that the levels of circulating total IgA in PASC patients are lower compared to controls. Preliminary findings are subject to change pending final analysis and results.

Conclusion/Discussion: Lower IgA antibodies in PASC patients suggest that these antibodies may be sequestered in the peripheral circulation, promoting thrombosis. Comparison with the levels of circulating B-cells producing IgA, will define whether the decreased IgA is caused by sequestration or by a decrease in B-cells generating these antibodies.

Key Topics:

• Assay and in vitro studies to gain mechanistic insights
• Chronic immune dysfunction
• Clinical assessment and pathogenesis of clinical manifestations
• Collaborative and systems biology approaches
• Studies of vascular injury, thrombosis, and other potential mechanisms of Long COVID