INFECT: exploratIoN oF (epi)-gEnetic changes Contributing To long COVID-19

SARS-CoV-2 has been rapidly spreading around the globe counting >55million infections and >1 million deaths, with continuously rising numbers. A sizable fraction of infected subjects develops viral pneumonia with signs of acute respiratory distress syndrome, which – in severe cases – leads to respiratory failure and death. While tremendous efforts are made to probe the underlying molecular mechanisms of acute COVID-19 disease (SHORT COVID-19), it now becomes clear that hospital discharge is not yet the end of suffering for patients. Alarming numbers of SHORT COVID-19 survivors present with ongoing, partly worsening afflictions, ranging from neurological disorders to respiratory difficulties and organ damage (LONG COVID-19). The emergence of LONG COVID-19 calls for urgent research to understand the drivers of these long-term consequences. Due to the protracted nature of LONG COVID-19, and based on preliminary data, I hypothesize that (epi)-genetic alterations contribute to LONG COVID-19. Using state-of-the-art technologies, I will probe SHORT COVID-19 lungs for epigenetic and genetic changes specifically in endothelial and immune cells – critical players in SHORT COVID-19 progression. Moreover, I will detect which changes persist in LONG COVID-19 patients, and validate their functional impact. The proposed project will reveal unprecedented insights into (epi)-genetic changes associated with LONG COVID-19, and will pave the way for novel therapeutic avenues for this disease.