Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments

Anti-SARS-CoV-2 monoclonal antibodies (mAbs) targeting Spike protein of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been utilized in the early treatment of COVID-19. However, the impact of these treatments on viral adaptations and the role of host immunity in selecting and sustaining these mAb-evading mutations has not been sufficiently addressed. Here, we describe development of several evasive Spike RBD mutations with remarkable speed and with high specificity to the targeted mAb binding sites. Several host-driven factors, such as a compromised immune system with downregulated proinflammatory cytokines and a growth factor-driven healing-promoting milieu, strongly correlate with occurrence of de novo mutations. Therapeutic mAbs with high neutralizing capacity against the infecting variant were also the ones that most efficiently selected for evading mutants.