Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery

Abstract

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.

Fig. 1. Kinetics of SARS-CoV-2 viral-specific antibodies up to 1 year.

SARS-CoV-2 infected individuals who attended the follow-up program were included in this analysis. a–c RBD-IgM, IgA, and IgG changes since symptom on-set. x-axis, follow-up time (day). y-axis, antibody titer (COI cut-off index; or arbitrary unit, AU/ml). The shaded regions represent the in-patient stage. The average values in the 1-month, 3-month, 6-month, and 12-month stages were labeled. P values (two-tailed) were shown. Mild (black dots), moderate (blue dots), and severe (red dots) symptoms. d Full-length spike-IgG changes since symptom on-set. x-axis, follow-up time (day). y-axis, antibody titer (AU/ml). e Correlation of RBD-IgG and Spike-IgG. In-hospital stage (black), 1-month follow-up (red), 3-month follow-up (blue), 6-month follow-up (purple), 12-month follow-up (green). Pearson r number and p value (two-tailed) were shown. f Longitudinal analysis of RBD-specific IgG between patients with high titer (RBD-IgG >1000 AU/ml, orange circle) and patients with low titer (RBD-IgG <1000 AU/ml, empty circle). g Longitudinal analysis of RBD-specific IgG between severe patients (red circle) and moderate patients (pink circle). Lines in x-axis and y-axis in a–e indicate the cut-off values. a–d, Mean values were labeled for each column. f, g, Data were presented as median with interquartile range. An unpaired t-test with Welch’s correction analysis was applied, and p values (two-tailed) were labeled. Source data are provided as a Source Data file.

Fig. 2. Longitudinal analysis of serum protection against SARS-CoV-2 infection.

Serum collected from multiple time points were tested against alive SARS-CoV-2 virus infection. a Microneutralization assay was performed using an alive SARS-CoV-2 infection cell culture system. y-axis, serum dilution folds. Data were presented as mean value ± SEM. Colored dots represent disease severity. Mild (blank dots), moderate (blue dots), and severe (red dots) symptoms. An unpaired t-test with Welch’s correction analysis was applied, and p values (two-tailed) were labeled. b Correlation of microneutralization (dilution folds) and RBD-IgG (arbitrary unit, AU/ml). A total of 475 pairs were analyzed, and Pearson r and p value (two-tailed) were shown. Lines in x-axis and y-axis in a and b indicate the cut-off values. Source data are provided as a Source Data file.

Fig. 3. SARS-CoV-2 specific T cells response in recovered COVID-19 patients.

a Representative ELISpot well images displaying IFNγ-secreting cells. N, S1, and S2, Synthetic overlapping peptide pool of nucleocapsid (N), Spike 1 subunit (S1), and 2 (S2). Con A, Concanavalin A positive control. b Spot numbers of IFNγ-secreting cells indicating the reduction in SARS-CoV-2 specific immune response over time. The numbers are the sum of N, S1, S2-stimulated wells. Data were presented as median with interquartile range. c Raincloud plots show different T cellular response levels among three peptide pools at different time points of follow-up. d Waffle dot plot showing composition percentage of the SARS-CoV-2 response during 1-year follow-up. Statistics by Mann–Whitney U-test. P value (two-tailed) were shown. b, c Data were represented as box-and-whisker plots (median with interquartile, upper-limit, and lower-limit). Source data are provided as a Source Data file.