SARS-CoV-2 evolution and immune escape in immunocompromised patients treated with exogenous antibodies

Background: SARSCoV2 mutations conferring escape from neutralizing antibodies can arise in immunocompromised patients with prolonged infection, but the conditions that facilitate immune escape are still not fully understood. Methods: We characterized endogenous immune responses, within host SARSCoV2 evolution, and autologous neutralization of the viral variants that arose in five immunocompromised patients with prolonged infection and B cell deficiencies. Results: In two patients treated with the monoclonal antibody bamlanivimab, viral resistance to autologous serum arose early and persisted for several months, accompanied by ongoing evolution in the spike protein. These patients exhibited deficiencies in both T and B cell arms, and one patient succumbed to disease. In contrast, we did not observe spike mutations in immunologically important regions in patients who did not receive exogenous antibodies or who received convalescent plasma and had intact T cell responses to SARSCoV2. Conclusions: Our results underscore the potential importance of multiple factors the absence of an effective endogenous immune response, persistent virus replication, and selective pressure such as single-agent bamlanivimab in promoting the emergence of SARS-CoV-2 mutations associated with immune evasion. These findings highlight the need for larger clinical studies in immunocompromised populations to better understand the ramifications of different therapies. Our results also confirm that patients with B cell deficiencies can elicit effector T cells and may suggest an important role for T cells in controlling infection, which is relevant to vaccines and therapeutics.