High CD4⁺ T-cell Responses in Seronegative Individuals Following SARS-CoV-2 Exposure during a Dormitory Outbreak
International Journal of Infectious Diseases, 2025
Teng O., Quek A., Ooi D., Wang S., Fragata L., Ng I., Cui J., Chen J., Hartman M., Hutchinson P., Tambyah P., Seet R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Objectives
We studied individuals who remained uninfected by SARS-CoV-2 despite repeated exposures during a May-July 2020 dormitory outbreak in Singapore.
Methods
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.
Results
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.
Conclusions
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.