“Monozygotic twins discordant for severe clinical recurrence of COVID-19 show drastically distinct T cell responses to SARS-Cov-2”

Abstract

ABSTRACT Background Clinical recurrence of COVID-19 in convalescent patients has been reported, which immune mechanisms have not been thoroughly investigated. Presence of neutralizing antibodies suggests other types of immune response are involved. Methods We assessed the innate type I/III IFN response, T cell responses to SARS-CoV-2 with IFNγ ELISPOT, binding and neutralizing antibody assays, in two monozygotic twin pairs with one COVID-19 recurrence case. Results In pair 1, four months after a first mild episode of infection for both siblings, one displayed severe clinical recurrence of COVID-19. Twin pair 2 of siblings underwent non-recurring asymptomatic infection. All fours individuals presented similar overall responses, except for remarkably difference found in specific cellular responses. Recurring sibling presented a reduced number of recognized T cell epitopes as compared to the other three including her non-recurring sibling. Conclusions Our results suggest that an effective SARS-CoV-2-specific T cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19. Besides, adaptive immunity can be distinct in MZ twins. Given the rising concern about SARS-CoV-2 variants that evade neutralizing antibodies elicited by vaccination or infection, our study stresses the importance of T cell responses in protection against recurrence/reinfection. Key points Immune parameters leading to COVID-19 recurrence/reinfection are incompletely understood. A COVID-19 recurrence case in a monozygotic twin pair is described with an intact antibody and innate type I/III Interferon response and drastically reduced number of recognized SARS-CoV-2 T cell epitopes.