SARS-CoV-2 antibody and T cell responses one year after COVID-19 and the booster effect of vaccination: A prospective cohort study

Abstract

Objectives: First, to describe SARS-CoV-2 T cell and antibody responses in a prospective cohort of healthcare workers that suffered from mild to moderate COVID-19 approximately one year ago. Second, to assess COVID-19 vaccine-induced immune responses in these prior-infected individuals.

Methods: SARS-CoV-2-specific T cell and anti-SARS-CoV-2-Spike-RBD immunoglobulin G (IgG) responses in blood were determined before COVID-19 vaccination with mRNA-1273, BNT162b2, Ad26.CoV2-S or ChAdOx1-S, two weeks after first vaccination, and after second vaccination.

Results: 55 prior SARS-CoV-2 infected and seroconverted individuals were included. S1-specific T cell responses and anti-RBD IgG were detectable one year post SARS-CoV-2 infection: 24 spot-forming cells per 10⁶ peripheral blood mononuclear cells (SFCs/10⁶ PBMCs) after S1 stimulation and anti-RBD IgG concentration of 74 (IQR 36-158) IU/mL. Responses after the first and second vaccination were comparable with S1-specfic T cell responses of 198 (IQR 137-359) and 180 (IQR 103-347) SFCs/10⁶ PBMCs, and IgG concentrations of 6792 (IQR 3386-15,180) and 6326 (IQR 2336-13,440) IU/mL, respectively. These responses retained up to four months after vaccination.

Conclusions: Both T cell and IgG responses against SARS-CoV-2 persist for up to one year after COVID-19. A second COVID-19 vaccination in prior-infected individuals did not further increase immune responses in comparison to one vaccination.

Keywords: Antibody; COVID-19; Immunity; SARS-CoV-2; T cell; Vaccination.

Fig. 1

Study design. (A) Timeline of the study. Blood was collected and immune responses were determined at three time points: before vaccination (t0) and two weeks after the first (t1) and second (t2) vaccination. (B) Flow diagram showing the population and sample size of the study.

Fig. 2

SARS-CoV-2-specific T cell and antibody responses one year after mild to moderate COVID-19. (A) T cell response magnitude of 32 COVID-19 recovered HCWs to tested SARS-CoV-2 antigens after stimulation for 16–20 h in the ELISpot assay. Each dot represents a COVID-19 convalescent HCW, and doughnut charts represent the proportion of HCWs having none, weak, strong, or very strong responses to tested antigen. Black lines indicate the median with IQR, and data statistical significance was determined using Kruskal-Wallis test with Dunn's post-hoc analysis. (B) Bar chart representing the proportion of HCWs that showed at least weak T cell responses. (C) Associations between antigen-specific responses assessed by Spearman's rank correlation coefficient (r). (D) The magnitude of anti-RBD IgG serum concentrations. One serum sample failed in the ELISA, leaving 31 HCWs in the antibody assessment. Black lines indicate median with IQR. (E) Associations between S1-specific T cell and anti-RBD IgG responses assessed by Spearman's rank correlation.

Fig. 3

Vaccine-induced SARS-CoV-2-specific T cell and antibody responses in COVID-19 convalescent HCWs. (A) T cell responses and anti-RBD IgG concentrations (B) median 5 (IQR 2–26) days before (t0) and median 15 (IQR 14–17) days after (t1) one dose of Ad26.COV2-S (n = 11), mRNA-1273 (n = 8), ChAdOx1-S (n = 3), or BNT162b2 (n = 1) vaccine. (C) T cell responses and (D) anti-S1 IgG concentrations against SARS-CoV-2 antigens median 15 (IQR 14–17) days after first vaccination (t1) and median 14 (IQR 14–17) days after second administration (t2) of mRNA-1273 (n = 8) or ChAdOx1-S (n = 4) vaccines. Median number of days between first and second vaccination is 30 (IQR 27–34). Association between S1-specific T cell responses and anti-RBD IgG concentrations at (E) t1 and (F) t2 assessed by Spearman's rank correlation. Statistical significance is determined using Wilcoxon signed-rank test (A-D).

Fig. 4

Persistence of vaccine-induced SARS-CoV-2-specific T cell responses in COVID-19 convalescent HCWs. (A) S1-specific T cell and anti-RBD IgG responses of COVID-19 convalescent HCWs (n = 16) who received two BNT162b2 vaccinations 68–127 days before blood collection. (B) Comparison of SARS-CoV-2 antigen-specific IFNγ responses. Black lines indicate median with IQR, and statistical significance was determined using Mann-Whitney U test. (C) Association between T cell and anti-RBD IgG responses was assessed by Spearman's rank correlation.