Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Abstract

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.

Down but far from out: The durability of SARS-CoV-2 immunity after asymptomatic infection

“…The authors did find reduced T cell responses in asymptomatic individuals at later time points after infection, but no differences early after infection. As stated by Le Bert et al (2021), these data "further support the accumulating evidence that the quantity of SARS-CoV-2-specific T cells is not proportional to disease severity during the early phase of infection." Secondarily, though statistically reduced over time relative to their symptomatic counterparts, the T cell responses in asymptomatic individuals were by no means negligible and showed enhanced cytokine production, as noted above.…”

“…However, these previous reports also noted differences in the rate at which the antibody response to N or the spike protein change over time. In the present report, Le Bert et al (2021) took the approach of monitoring virus neutralization as a surrogate for spike-specific antibodies.…”

“…The Emerging Infectious Disease collaborative program between Duke University and the National University of Singapore (DUKE-NUS) teamed up with other research institutes in Singapore to follow the immune responses of residents from a migrant worker dormitory during the initial months of the SARS-CoV-2 outbreak. Le Bert et al (2021) were able to identify and track the immune responses of those that initially reported as seropositive as well as those that seroconverted during the course of the study, providing reasonable estimates for the duration of time elapsed after infection. Because of the regular screening for symptoms at the dormitory (see below), they were able to reasonably satisfy the concern that the data obtained were not influenced by disease severity.…”

“…This is actually not a trivial accomplishment, mostly because validating any infection as truly asymptomatic (and not just "presymptomatic") is far from straightforward. The present study by Le Bert et al (2021) accomplished this by enrolling migrant workers quarantined in a dormitory in Singapore, allowing them to establish the general timing of seroconversion and related symptomology; each participant was monitored twice daily for temperature and pulseOx readings and evaluated by medical posts within the dormitory. Further, each worker "received a monetary compensation provided by the Singapore government," hopefully avoiding any "economic incentive to report an asymptomatic state for fear to economical loss."…”

“…SARS-CoV-2-specific T cells from asymptomatic patients presented increased IFN-γ and IL-2 production, while increased inflammatory cytokines were secreted by SARS-CoV-2-specific T cell in symptomatic individuals. Figure is reprinted with permission (Le Bert et al, 2021).…”