Grant: Project Grant

COVID-19 and Post COVID Condition (PCC) are recent pandemics which have created a global tide of cardiovascular, pulmonary, and neurocognitive disorders. SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is the coronavirus behind the COVID-19 pandemic which 'hijacks' the angiotensin converting enzyme 2 (ACE2) as its dominant receptor to infect various cells. SARS-CoV-2 targets a number of organs including the cardiovascular (CV) system, and it persists beyond the acute infection leading to CV disease. About 15-20% of symptomatic and asymptomatic COVID-19 survivors develop the PCC (Long COVID) with features that include dyspnea, fatigue, chest pain, cognitive decline, and multiorgan damage mostly in middle age/older patients. While men have a worse prognosis compared to women with acute COVID, female sex is associated with worsened outcomes in PCC. We lack therapies that protect and reverse critical end-organ damage and dysfunction in patients with PCC. We proposed to use two rodent models (males and females) to fully capture the phenotype of PCC patients and to test novel therapeutics. We have established COVID models in aged male Balb/c mice and Syrian hamsters and showed that they capture the basic features of COVID in patients. We identified molecular and tissue alterations resulting in cardiovascular dysfunction, neurocognitive decline in association with gut microbiota and metabolic changes. We have identified taurine deficiency and loss of ACE2 in the gut as important mechanistic changes linked to PCC. We will test taurine and ACE2 probiotics supplementation as novel therapies for PCC. Our study will allow us to understand how to better treat these conditions when they happen, and can reduce the number of people who suffer from COVID complications. Understanding what treatments are safe for patients with COVID-related illness will reduce the burden of symptoms and comorbidities.