Tu178 - Investigating Links Between Persistent Symptoms After COVID-19 and Longitudinal Changes in Memory T Cell Responses to EBV, CMV, HSV-1, and sars-cov-2

Erika Smith – Microbiology – Boston University Chobanian & Avedisian School of Medicine; Christina McConney – Microbiology – Boston University Chobanian & Avedisian School of Medicine; David Bean – Microbiology – Boston University Chobanian & Avedisian School of Medicine; Anna Belkina – Flow Cytometry Core Facility – Boston University Chobanian & Avedisian School of Medicine; Jennifer Snyder-Cappione – Microbiology – Boston University Chobanian & Avedisian School of Medicine

Abstract Text: Post-acute infection syndromes (PAISs) have long been observed following acute infections with bacteria, viruses or other microbes. Overlapping core symptoms across different PAISs suggest underlying mechanism(s) that is putatively independent of the causative agents. During the COVID-19 pandemic, accumulating reports of post-acute sequelae of SARS-CoV-2 infection (PASC), also known as “long Covid”, have provided new clues for the pathogenesis of PAISs, but the mechanistic drivers of persistent symptoms are still unclear. Here, we evaluated temporal changes in the memory T cell repertoire, in both frequency and functional signatures, of five individuals initially infected with SARS-CoV-2 in the spring of 2020 (three outpatient, two hospitalized), with three participants showing evidence of PASC. Longitudinal T cell responses were quantified as the frequencies of cytokine producing cells after overnight (ex vivo) stimulation of PBMCs with peptide pools from cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1) and SARS-CoV-2; cell readouts were obtained using intracellular cytokine staining (ICS). PBMCs were collected from multiple timepoints from acute illness to 12-25 months post-infection. Our unique dataset serves as an indirect readout of viral replication and provides insights to two possible explanations for PASC: the reactivation of latently infected viruses during and after the acute SARS-CoV-2 infection, and the persistence of SARS-CoV-2 antigens triggering chronic inflammation. For future studies, longitudinal T cell responses after acute infections with other microbes will be assessed in a larger cohort to determine the specificity of the findings to SARS-CoV-2 infection.