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Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection

https://www.nature.com/articles/s41467-021-22036-z

Abstract

The proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection.

Results

Although the close contacts in our cohort were all negative in both nucleic acid test (NAT) and SARS-CoV-2 antibody screening, the possible exposure of these individuals to the virus may have led to the generation of T cell immunity even in the absence of a successful infection. To test this possibility, we performed a 10-day in vitro peptide stimulation assay for 69 close contacts from 45 family clusters. The results show that 57.97% and 14.49% of close contacts contained virus-specific memory CD4+ and CD8+ T-cells, respectively. Notably, all close contacts developed responses at lower frequencies than 4%, while 64 (71.11%) and 32 (35.56%) of the 90 COVID-19 patients developed marked responses at the frequencies of higher than 4% for IFNγ+CD4+ T cells and IFNγ+CD8+ T cells, respectively.

exposure to SARS-CoV-2 can facilitate the establishment of the T memory immunity not only in COVID-19 patients, but also in some close contacts even in the absence of a successful infection.

Discussion

Close contacts, who are SARS-CoV-2-exposed, are often both NAT negative and antibody negative, indicating that SARS-CoV-2 failed to establish a successful infection within these individuals, presumably due to their exposure to limited numbers of viral particles or a short time of exposure. However, our analysis of the samples from 69 of these close contacts showed the presence of SARS-CoV-2 specific memory T-cell immunity. A similar observation was reported during the MERS epidemic where high-risk individuals (e.g., camel workers) who were NAT negative and antibody negative also developed significant levels of MERS-CoV specific memory T cells.

Importantly, our discovery of the presence of significant levels of SARS-CoV-2-specific memory T-cell immunity in a group of individuals (close contacts) who were exposed to but not infected by the virus highlights some unique characteristics in the dynamic interactions between SARS-CoV-2 and its human host.