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Objectives Antibody response to the first dose of BNT162b2 SARS‐CoV‐2 is greater in COVID‐19‐convalescent than in infection‐naïve individuals. However, there are no data about T‐cell response in individuals with pre‐existing cellular immunity. Methods We evaluated T‐cell responses in parallel with SARS‐CoV‐2 antibody level after first dose of BNT162b2 vaccine in 23 infection‐naïve and 27 convalescent healthcare workers (HCWs) previously included in a study about humoral and T‐cell immunity. Results Overall, the antibody response was lower in the infection‐naïve group than in convalescent individuals (18 895 vs 662.7 AU mL −1 , P < 0.001), and intermediate but significantly lower in convalescent HCWs with previous negative serology (25 174 vs 1793 AU mL −1 ; P = 0.015). Indeed, anti‐spike IgG titres after the first dose correlated with baseline anti‐nucleocapsid IgG titres (rho = 0.689; P < 0.001). Pre‐existing T‐cell immunity was observed in 78% of convalescent and 65% of the infection‐naïve HCWs. T‐cell response after the first dose of the vaccine was observed in nearly all the cases with pre‐existing T‐cell immunity, reaching 94% in convalescent HCWs and 93% in those with cross‐reactive T cells. It was lower in the infection‐naïve group (50%; P = 0.087) and in convalescent HCWs with negative serology (56%; P = 0.085). Notably, systemic reactogenicity after vaccination was mainly observed in those with pre‐existing T‐cell immunity ( P = 0.051). Conclusion Here, we report that the first dose of BTN162b2 elicits a similar S‐specific T‐cell response in cases of either past infection or cross‐reactive T cells, but lower in the rest of infection‐naïve individuals and in convalescent HCWs who have lost detectable specific antibodies during follow‐up.

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We investigated the duration of humoral and T-cell immune response in paired samples among 22 convalescent health care workers (HCWs). A median of 1.8 months after diagnosis, T-cell response was significantly lower in HCWs with early loss of antibodies (6 cases, 27%). After 5.1 months, antibodies decline was observed in 77% of cases (41% seroreverted; p&lt;0.01), and 36% have lost T-cell response (75% lost response to spike protein). Persistence of immune response was observed in those who developed a greater adaptative immune response. Our data point to the initial immune response as the relevant player in COVID-19 duration of protection.

Objective T-cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are observed in unexposed individuals. We evaluated the impact of this pre-existing cellular response on incident SARS CoV-2 infections. Methods Follow up study of 38 seronegative health care workers (HCWs) with previous evaluation of CD8+ and CD4+ T-cell response after stimulation with SARS-CoV-2 structural proteins. Infection was considered in presence of a positive reverse transcription (RT)-PCR test and/or confirmed seroconversion. Results Twenty of the 38 HCWs included (53%) had a previous specific CD8+ T cell response to peptides encompassing the spike (S) protein in 13 (34%), the membrane (M, 17, 45%), or/and the nucleocapsid (N, 3, 8%). During a follow up of 189 days (interquartile range, IQR, 172 to 195), 11 (29%) HCWs had a RT-PCR positive test (n=9) or seroconverted (n=2). Median duration of symptoms was 2 days (IQR, 0-7), and time to negative RT-PCR was 9 days (IQR, 4-10). Notably, six incident infections (55%) occurred in HCWs with pre-existing T-cell response (30% of those with cellular response), who showed a significant lower duration of symptoms (three were asymptomatic). Three of the six HCWs having previous T-cell response continued testing seronegative. All the infected patient developed a robust T-cell response to different structural SARS-CoV-2 proteins, especially to protein S (91%). Conclusion Pre-existing T-cell response does not seems to reduce incident SARS-CoV-2 infections, but it may contribute to asymptomatic or mild disease, rapid viral clearance and differences in seroconversion.