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.
Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. To date, efforts to overcome the virus are hampered by a lack of knowledge of several important aspects of SARS-CoV-2 infection, ranging from pathogen biology to host response and treatment options. Hence, further studies of the host immune response to SARS-CoV-2 are necessary. Focus on dissecting the innate immunity as well as the adaptive immune response to the whole viral antigenic repertoire could be essential in order to acquire in-depth understanding of the immune mechanisms leading to the control of this novel coronavirus and to improve treatment and design a tailored immune-therapy for SARS-CoV-2 patients. Therefore, through a prospective observational study of interferon antiviral activity and virus-induced inflammasome in a large cohort of SARS-CoV-2 patients compared to SARS-CoV-2 negative patients and healthcare workers, we will able to identify an IFN and inflammasome module that can be employed to predict disease activity. Our research project will able to contribute greatly to common understanding of the molecular mechanisms governing COVID-19 disease. Thus, our approch lays the foundation for the development of immunologic IFN and virus-induced inflammasome signatures that coud be useful in managing COVID-19 patients. We firmly believe that the clinical management of SARS-CoV-2 patients might be enhanced by the development of improved innate immunological markers and predictors of clinical severity of SARS-CoV-2 infection, which could assist clinicians in assessing disease activity. Our assessment of inflammatory response will be helpful to improve SARS-CoV-2 infection since inflammasome multiprotein complex represents a potential target for drug- or vaccine- base interventions for the control of viral replication. Therefore, identification of predictors (biomarkers) will be helpful to define immune correlates of protection and disease severity for effective triage of patients. Moreover, this project is based entirely on clinical research on SARS-CoV-2 positive patients and uses a simple, but innovative, scientific approach that makes sure it will get off the ground quickly and achieve to preliminary results faster.