High-dimensional immune profiling identifies circulating NK and T cell subpopulations associated with asymptomatic COVID-19 and absence of multiple long-term symptoms.

While severe COVID-19 is well-characterized, immune profiles of non-hospitalized, non-vaccinated individuals are less investigated. High-dimensional single-cell profiling and multiplex serum marker analysis characterized immune profiles according to outcome during acute infection and six months later. Lower IL-1RA and HGF levels, higher CD57+TIGIT+NKT, CD57+GrB+NKT, CD16+TIGIT+NK and CD4+CD57+GrB+ effector T-cell levels characterized asymptomatic infection. PMA + ionomycin induced higher frequencies of polyfunctional CD4+ and CD8+ effector T-cells in asymptomatic compared to moderate disease. Absence of multiple long-term symptoms was associated with higher CD16+TIGIT+NK-cell frequency, lower HGF levels and persisting high memory B and regulatory NK subpopulation levels. Higher frequency of CD16+TIGIT+ NK cells was in common for non-infected, asymptomatic, and individuals without multiple long-term symptoms. Compared to infected individuals, non-infected cases showed higher pre-existing T-cell responses to hCoV and SARS-CoV-2 peptides. This study contributes to increased understanding of protective immune responses in non-hospitalized COVID-19 cases, emphasizing the role of defined NK and T-cell subpopulations.