Defining the immune signatures in SARS-CoV-2 infected individuals in blood and tissues

Background: To date (23rd of March 2020), 170 countries confirmed the presence of infected individuals on their territory, and more than 333'000 people have already been infected worldwide. The number of deaths related to SARS-Cov-2 virus approximate 14'000 individuals. In Switzerland, 8'060 people were infected, and 66 people already died. Every day, 50'000 individuals are infected worldwide with SARS-CoV-2 and about 5% of them develop severe acute respiratory syndrome and no predictive markers of such evolution are currently known (https://www.bag.admin.ch/). The fine characterization of the immune signatures associated with intensive care unit (ICU) and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally may help to improve the care of infected patients.Hypotheses: Severe SARS-CoV-2 infection is due to dysregulated immune responses that might be identified at the time of admission/diagnosis.Objectives: In this context, the proposed research project plans to 1) define specific ex vivo immune signatures associated with ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally ; 2) characterize the innate and adaptive CD4 and CD8 T-cell responses of ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally; 3) establish whether the specific immune signatures identified in Objectives 1-2 are associated with the clinical presentation of patients with SARS-CoV-2 infection; and 4) to characterize the organ distribution, morphology and immunopathological features of the tissue lesions in SARS-CoV-2 infected individuals succumbing to disease, and to correlate with immune signatures and responses described above.Experimental strategy: To address these objectives, we will assess the ex vivo cellular and serum immune signatures, the blood transcriptome and will define the SARS-CoV-2-specific CD4 and CD8 T cell profile of ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally, and perform ex vivo studies on biological fluids and tissue obtained from autopsies.Expected outcome: The proposed research project has the potential to substantially advance the delineation of immune dysregulation observed in SARS-CoV-2-infected individuals who underwent severe acute respiratory syndrome. In particular, the proposed research project will define the specific immune signatures associated with ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis and longitudinally.Significance of the research project: To date, SARS-CoV-2 infection remains largely poorly characterized. In this context, this research project has the potential to provide key information on the immunological signatures associated with ICU and non-ICU hospitalized SARS-CoV-2 infected individuals at the time of admission/diagnosis, which may help improve the care of infected patients and may help to guide the selection of a preventive vaccine. These results will improve the diagnosis and follow-up of affected patients. The strength of the proposed research project relies on the unique combination of the clinical expertise of the Division of Immunology and Allergy, the Service of Infectious Diseases and the Institute of Pathology of Lausanne University Hospital and the use of the most modern technologies to comprehensively characterize the immunological parameters associated with SARS-CoV-2 infection.