Ricerc@Sapienza

The beginning of 2020 has seen the emergence of COVID-19, an outbreak caused by a novel coronavirus, SARS-CoV-2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. Effective innate immune response against viral infection relies heavily on the interferon (IFN) type I-III response, inflammasome activation and their downstream cascade that culminates in controlling viral replication and induction of effective adaptive immune response. A successful mounting of IFN response and a potent inflammatory stimulus should be able to suppress viral replication and dissemination at an early stage. On the other hand, deregulation in IFN response can cause detrimental immunopathology and contribute to disease severity. In this project we hypothesize that SARS-CoV-2 utilizes strategies in order to modulate the host innate immune response, especially in dampening the type I IFN response. This delayed or dampening type I IFN responses could impinge upon adaptive immune activation and favour prolonged SARS-CoV-2 persistence which exacerbates inflammatory responses. At the same time, biased Th2 type response might also favours poor outcome of the COVID-19. With this purpose, we plan to perform a comprehensive examination of patients hospitalized for COVID-19 in order to study the following objects: i) characterization of airway and blood type I/III IFN signature; ii) delineation of virus-induced inflammasome activation in respiratory and pheripheral blood lymphocytes; iii) evaluation of Th1/Th2 response in patients' blood. Understanding of the effects of SARS-CoV-2 on the overall innate immune response with the final aim to shed new light on COVID-19 pathogenesis and design a tailored immune-therapy for SARS-CoV-2 infected patients.