Deciphering immune responses in COVID-19 patients to identify immune correlates of protection and susceptibility for targeted therapeutics

COVID-19 pandemic has already infected >30 M people, claimed >0.9 M lives and paralyzed economies globally. Despite the prior work on understanding how the virus impacts the immune system many questions have remained unanswered and, therefore, substantial efforts are urgently needed to understand them. We yet to understand immune correlates of recovery and protection from COVID-19 infection. Rationally design and evaluate novel vaccines and immunotherapies require a deeper understanding of how the virus interacts with the immune cells. Therefore, we plan to conduct a comprehensive study in detail at the cellular and molecular levels in COVID-19 patients with asymptomatic, mild, moderate, severe, and critical disease in our well-established longitudinal cohorts. We have already assembled a team of internationally-recognized immunologists, virologists, pulmonary medicine, intensive care and infectious disease experts to jointly address some of these issues.  Main Objective: To define protective and long-lasting immunity against SARS-CoV-2 and delineate detrimental immunopathology in COVID-19 by undertaking in-depth immunological studies combined with viral studies and clinical data from the natural SARS-CoV-2 infection across different patient groups. Detailed analyses of immune correlates of protection have the potential for a major impact, especially for those at risk from severe COVID-19. At the conclusion of this work in 3 years, we expect to have gained a thorough understanding of immune responses associated with the patient recovery and severe disease caused by SARS-CoV-2, especially in high-risk groups; fundamental for informing public-health policies needed to limit disease spread and protect high-risk groups.  Feasibility: Collectively, we have established the required breadth of expertise and cutting-edge techniques for COVID-19 research, as shown by our recent under review publications (Nature Communications x2).