P-1978. Long-Term Mast Cell Activation Patterns in Systemic and Tissue-Resident Compartments Following COVID-19: Insights from a 2-Year Post-Infection Study

Abstract Background The pathogenesis of Post-COVID syndrome (PCS) following mild coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) remains unclear. In particular, the involvement of activated mast cells (MC) in the highly angiotensin converting enzyme 2 (ACE2) expressing small bowel, the largest lymphoid organ, might be significant in PCS pathogenesis. This study aimed to elucidate the role of activated MC, residual SARS-CoV-2 spike (S) protein and zonulin (a marker for impaired intestinal integrity), in the context of PCS, examining peripheral blood (PB) and terminal ileum (TI) 2 years post-infection. Methods In this cross-sectional, controlled study, paired PB and TI samples were obtained from 21 SARS-CoV-2 convalescents with (PCS+) and 11 without PCS (PCS−). CD117+CD25+ activated MC and residual S protein were assessed using fluorescent immunohistochemistry on sections of the the ileal tissue from the gut. Tryptase, zonulin and S protein were quantified in serum by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed frequencies of T-cells (CD3+CD4+ (TCD4), CD3+CD8+ T-cells (TCD8)) and CCR7±CD27± memory subsets (TCM: T central memory, TEM: T effector memory) on mononuclear cells of PB and TI. Results Among PCS+ and PCS−, median follow up was 22 and 18 months post-infection, 81% and 73% were female, and 57% and 55% had pre-existing conditions of which arterial hypertension, chronic lung disease and diabetes mellitus were the most frequent. Compared to PCS−, PCS+ expressed significantly more MC (p< 0.0001) in ileal sections, along with elevated levels of tryptase (p=0.0196) and zonulin (p=0.024) in PB. S protein, by contrast, was undetectable in PB of PCS+ and PCS− even 2 years post-infection. In TI however, the frequency of tissue-resident S protein-infected cells was significantly higher in PCS+ compared to PCS− (p=0.0135). Interestingly, systemic tryptase levels correlated positively to elevated TCM in TI (r=0.7407, p=0.0034). Conclusion Elevated MC activity and S protein in the TI, along with increased tryptase and zonulin levels in PB, indicate ongoing immune activation and intestinal damage in the TI of PCS+. Understanding the role of tissue-resident MC in PCS pathogenesis could lead to targeted therapies. Disclosures All Authors: No reported disclosures