A Systematic Assessment of the Drivers of COVID-19 in the Swiss HIV Cohort Study: Epidemiology, Immunology, and Genetics

We propose to conduct a systematic study of seroprevalence, determinants of clinical outcome and potential preventive influence of antiretroviral therapy in people living with HIV (PLWHIV) during the COVID-19 pandemic utilizing the extensive sample and data collection of the Swiss HIV Cohort Study (SHCS). In a large, systematic plasma screen for the presence of anti-SARS-CoV-2 binding and neutralizing antibodies, we will be able to not only assess the seroprevalence of SARS-CoV-2 infection in over 2000 individuals but also elucidate many aspects of COVID-19 epidemiology, pathogenesis, and immunology. The comprehensive patient data that are available within the investigated patient cohorts will empower our study to perform extended systematic analyses that go beyond a mere frequency analysis of antibody responses but will also allow to identify factors associated with severity of disease and disease outcome. Moreover, it will allow us to gain information on future SARS-CoV-2 prevention strategies. Aim A: Defining seroprevalence and characterizing antibody responses against SARS-CoV-2 in the SHCSWe aim to assess the presence of anti- SARS-CoV-2 binding (A1) and neutralizing antibodies (A2) in the Swiss HIV Cohort study (SHCS). We will be able to assess experimentally reactivity against SARS-CoV-2, and cross-reactivity against the circulating coronaviruses (CoVs) and the past SARS and MERS epidemics. Comparing this to the vast experimental data generated for HIV binding and neutralizing antibodies [1-3] will allow for a multilayered understanding of the humoral response to SARS-CoV-2 and HIV in PLHIV. Moreover, with this thoroughly described cohort, we will be able to assess the demographic and epidemiological determinants of SARS-CoV-2 seroconversion within Switzerland. We will further investigate whether binding antibody responses also correlate with neutralization (A2). This will help us define whether binding is a predictor for neutralization and ultimately gain insights into responses relevant for vaccine efficacy. Finally, we will test the association between SARS-CoV-2 and the rich epidemiological, demographic, behavioral, and genetic data in the SHCS and thereby elucidate the drivers of the ongoing SARS-CoV-2 epidemic (A3). Aim B: Are there any protective effects of antiretroviral therapy against SARS-CoV-2?Based on the findings of Aim A we will assess the effect of antiretroviral drug efficacy on SARS-CoV-2 infection probability. This analysis will help us understand whether protease inhibitors do have potential as preexposure prophylaxis in SARS-CoV-2.Aim C: Systematic description of determinants of clinical outcome and reinfection in HIV/SARS-CoV-2 positive patientsWe intend to perform a detailed analysis of possible risk factors for the development and severity of COVID-19 (C1) and for re-infection of SARS-CoV-2-seropositive PLHIV (C2) in the SHCS by analyzing seroconversion and additional factors such as comorbidities, HIV- specific variables, human genetics, and co-medication.