COVID-19 is a viral disease with high global death toll and significant socio-economic consequences. The SARS-CoV-2 virus that causes the disease appears to induce devastating cardiovascular, renal and neurological complications and results in significant mortality rates in older patients and those with co-morbidities (e.g. hypertension, cardiovascular disease, obesity, and diabetes). Mechanistic understanding of the pathophysiology that triggers this catastrophic response is critical to tailoring appropriate therapies and to improving outcomes. Ultimately, new tools are urgently needed to monitor end-organ damage and disease progression in high-risk patients. RNA viruses like SARS-CoV-2 co-opt the cellular machinery of host cells to transcribe and translate more viral proteins. These viral proteins can be incorporated into extracellular vesicles (EVs) of host cells. We hypothesize that EVs released from infected host cells are decorated with SARS-COV-2 viral proteins; these EVs can stimulate T cell responses, trigger release of cytokines, and lead to end-organ damage. Moreover, these EVs may contain cell-specific RNAs from the infected cells, serving as a peripheral marker of tissue infection. EVs can be collected frequently and non-invasively from almost any accessible biofluid (e.g. blood, saliva, urine). EVs represent an attractive tool for monitoring the viral infection because EV proteins and extracellular RNA (exRNA) cargo, rapidly change in response to a subjects’ physical status. This project aims at characterizing viral EV subpopulations and organ specific EV subpopulations in order to determine their role in disease progression and provide sensitive and selective peripheral biomarker of tissue infection.