Persistent COVID-19 symptoms minimally impact the development of SARS-CoV-2 specific cellular immunity

Abstract

SARS-CoV-2 represents an unprecedented public health challenge with many unknowns remaining regarding the factors that impact viral pathogenicity and the development of immunity after infection. While the majority of SARS-CoV-2 infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, a significant number of individuals experienced prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, especially within the cellular immune compartment. However, it is unclear if persistent mild-to-moderate COVID-19 impacts the development of virus-specific cellular immunity. To this end, we analyzed the development of SARS-CoV-2 specific cellular immunity in convalescent COVID-19 patients who experienced eight days or fewer of COVID-19 symptoms, or symptoms persisting for 18 days or more. We observed that the duration of COVID-19 symptoms minimally impacts the magnitude, antigen specificity, and transcriptional profile of SARS-CoV-2 specific cellular immunity within both the CD4+ and CD8+ T cell compartments. Furthermore, we observed that reactivity against the structural N protein from SARS-CoV-2 in convalescent COVID-19 patients correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63. These results provide additional insight into the complex processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses.