Pneumonia is the most common infection leading to hospitalization in intensive care units and the most common cause of death associated with infectious diseases in developed countries. Respiratory tract infections are associated with an increased risk of thrombotic events during hospitalization. Moreover, COVID-19 related pneumonia is associated with enhanced risk of thrombosis in both arterial and venous circulation, which may underlie in a higher risk of in-hospital mortality. The risk of cardiovascular complications in pneumonia is the highest among the elderly who typically display a hyperactive innate response and an ineffective adaptive response. Use of anti-inflammatory drugs is associated with a reduction of thrombotic risk in pneumonia. Beyond their hemostatic function, platelet have an important role in modulating inflammation.
The overarching hypothesis of the proposed project is that thrombotic complications in pneumonia are the result of a thromboinflammatory process in which platelets have both an early pro-inflammatory role and a late pro-thrombotic role.
Specific Aims:
Aim 1: To characterize the hemostatic and immune phenotype of platelets in community-acquired pneumonia (CAP) patients and patients with Covid-19 related pneumonia with and without thrombotic complications.
Aim 2: To identify the determinants of NETs formation that predispose to thrombosis in CAP and patients with Covid-19 related pneumonia.
Aim 3: To understand how immunomodulators (as glucocorticoids) lower the risk of thrombotic complications in CAP patients and patients with Covid-19 related pneumonia.
Dissecting the sequence of events of the thromboinflammatory process in pneumonia is of high clinical significance. We expect to understand why some patients are more susceptible to thrombosis than others and to identify markers of the platelet immune response that could be used as early biomarkers of thrombotic risk and poor prognosis in pneumonia patients.
The overarching hypothesis of the proposed project is that thrombotic complications in pneumonia are the result of a thromboinflammatory process in which platelets have both an early pro-inflammatory role and a late pro-thrombotic role.
Dissecting the sequence of events of the thromboinflammatory process in pneunomia is highly significant and relevant from a clinical standpoint. First, we expect to understand why some patients are more susceptible to thrombosis than others and to identify markers of the platelet immune response that could be used as early biomarkers of thrombotic risk and poor prognosis in pneumonia patients. Secondly, our findings will explain the mechanism of action of currently used anti-inflammatory drugs, such as glucocorticoids, and help devise novel strategies to target thrombosis in pneumonia by inhibiting the immune function of platelets without affecting hemostasis. Last but not least, our findings may apply to the treatment of patients infected with Sars-Cov2. In the past 20 years there have been 3 outbreaks of coronavirus infections causing severe acute respiratory syndrome with thrombotic complications. Thus, understanding how pulmonary infections cause thromboinflammation may improve the management and treatment of patients in current and future outbreaks.