Longitudinal single B cell studies across the trajectory of COVID-19 to identify SARS-CoV-2 specific monoclonal antibodies and long-term memory formation

The development of neutralizing humoral immunity is suggested to play a pivotal role in the protection from COVID-19 and the generation of immunological memory is basis for future protection from the disease. However, to date, the genetics of the acute and memory B cell response are unknown, few potential neutralizing monoclonal antibodies are described and the capacity of humans to develop B cell memory against SARS-CoV-2 is still elusive. Here we will prospectively and longitudinally follow a cohort of (>200) healthcare workers at the intestinal diseases department of the University Hospital Bern. By monitoring the course of SARS-CoV-2 infection status in this cohort, we will assess their acute and memory B cell response before, during and after COVID-19 infection. We have ethical permission to sample peripheral blood of consenting personnel and measure SARS-CoV-2 viral status weekly using in-house diagnostics with consumables that are designed not to conflict with the clinical lab pipelines. By determining the single B cell repertoire in the periphery before the onset of clinical or virus-positive disease we will be able to determine the immunological baseline for each study participant at single cell level. This baseline will be compared to acute and memory B cell populations during the active disease to identify hallmarks of the B cell repertoire associated in patients with asymptomatic, mild or severe COVID-19 infection. After resolution of the infection, subjects will be sampled at various timepoints up to half a year and the potential hallmarks of the B cell repertoire will be identified in the peripheral memory B cell pool. The data will provide a description of the acute B cell response to SARS-CoV-2 at single cell level and can determine if cellular B cell memory is formed in COVID-19 infection. We hypothesise that the data will be able to describe immunogenetic determinants of the B cell response that can discriminate between protected from non-protected individuals and/or severe from non-severe cases. Further, it will create a resource that will contribute to global databases guiding potentially neutralizing SARS-CoV-2 monoclonal antibodies.