The SARS-CoV-2 virus causes COVID-19, which ranges from mild initial symptoms to severemulti-organ dysfunction. While some patients recover to their baseline states, othersdevelop a long COVID, or post-acute sequelae of SARS-CoV-2 (PASC) consisting of symptomspersisting >2-6 months post-infection. PASC symptoms include post-exertional malaise,fatigue, and heart palpitations as well as incident GI disorders, cognitive dysfunction,and arthritis. Based on prevalence/incidence studies, it is estimated that more than 30million people in the US have ever developed PASC with 10-11% of patients or 11 millionpeople continuing to feel symptoms to the present day10. SARS-CoV-2 vaccines are only~32% effective against infection at 4 months post-vaccination11, only 15% effectiveagainst the development of PASC12, and only 20% of American adults have received anupdated booster as of December 202313. It is therefore imperative that the scientificcommunity make progress in identifying underlying causes of PASC to develop effectivetreatments.This study will identify microbial metabolites associated with PASC-mediated gutdysbiosis and establish a tractable in vitro model to test T cell-gut epithelium dynamicsto develop novel bio-therapeutics for multiple post-viral conditions. This case-controlstudy will collect biospecimens (matched stool & blood) samples from 400 people with andwithout long COVID (200 participants/group) to understand how COVID-induced dysbiosisimpacts symptom severity, immune suppression, and gut barrier dysfunction both ex vivoand in vitro.