Summary The novel coronavirus SARS-CoV-2 causes the COVID-19 pandemic. The virus infects through the respiratory tracts. While most COVID-19 patients display no or mild clinical symptoms, a small percentage develop severe immune-mediated pathological complications, which could lead to injury and failure of the lung and various important organs and account for the majority of COVID-19 deaths. Understanding how different components of the immune system are involved in the viral control and pathological development is crucial for our understanding of pathogenesis of the disease and developing preventative and therapeutic strategies. In this grant application, we propose to dissect involvement of CCR10-regulated mucosal IgA antibody responses in SARS-CoV-2 infection clearance versus immune-pathological development using mouse models in two specific aims. In the Aim 1, we will determine the role of CCR10-regulated primary mucosal IgA responses in SARS-CoV-2-infection clearance and immunopathological development. In the Aim 2, we will determine the role of CCR10- regulated memory mucosal IgA responses in SARS-CoV-2 infection and immune-pathological development. The findings of our proposed study will not only help our understanding of involvement of mucosal IgA responses in clearance of the viral infection and pathogenesis of COVID-19 but also provide a guide on future development of vaccination strategies to induce proper IgA response for the disease prevention.

Narrative The novel coronavirus SARS-CoV-2 causes the COVID-19 pandemic. While most COVID-19 patients display no or mild clinical symptoms, a small percentage of them develop severe pathological complications and even death mostly due to dysregulated immune responses. Our proposed studies into the involvement of local tissue antibody responses in the viral control and pathological development will aid our understanding of pathogenesis of the COVID-19 disease and developing preventative and therapeutic strategies.