High CD4⁺ T-cell Responses in Seronegative Individuals Following SARS-CoV-2 Exposure during a Dormitory Outbreak

We studied individuals who remained uninfected by SARS-CoV-2 despite repeated exposures during a May-July 2020 dormitory outbreak in Singapore. We compared immune profiles of those with exposed seronegative (ESN) (negative PCR and serology), with non-infected and infected groups. Following the lifting of quarantine, incident infection rates were compared between the ESN and non-infected cohorts. The immune profiles of 135 men with ESN (repeated negative PCR and persistent seronegativity), and 98 non-infected men, and 139 infected men were examined (mean age 33 years). Men with ESN exhibited higher percentages of CD4+ T-cells and classical monocytes, alongside increased specific CD4+ T cell responses to the non-structural protein 12-3 region (NSP12-3) and spike peptides of SARS-CoV-2, compared with non-infection controls. Those with ESN did not differ in their IgG levels against endemic human coronaviruses compared with non-infection controls. Men in the ESN group were found to be less likely to become infected compared with non-infected controls (21% vs. 39%, hazard ratio 0.47 [95% CI 0.27-0.73]) after the lifting of quarantine measures. These findings highlight the possible importance of cellular immunity in conferring partial resistance to infection and support the development of T-cell-focused strategies for high-risk settings. NCT04446104.