Longevity of seropositivity and neutralizing antibodies in recovered MERS patients: a 5-year follow-up study

Abstract

Objectives: We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients.

Methods: We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens.

Results: The seropositivity rate persisted for up to 4 years (50.7-56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT₅₀, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection.

Discussion: The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.

Keywords: Antibody; Longevity; MERS-CoV; Neutralization; Spike.

Fig. 1

Kinetic changes in anti-S1 IgG responses and seropositivity rates of recovered MERS-CoV patients until 60 months after symptom onset. (A) The levels of serum spike-specific IgG were semi-quantitatively determined by calculating the optical density (OD) ratios. OD ratios <0.7 were considered negative, OD ratios >1.4 (grey line) were considered positive, and OD ratios ≥ 0.7 and ≤ 1.4 were considered intermediate. (B,C) The percentage of serum samples with negative (white), positive (black), and intermediate (gray) OD ratios in all participants (B) and in each clinical severity group (G-I–G-III), (C) at each time point (G-I: n = 9–18, G-II: n = 17–33, and G-III: n = 12–18) are shown.

Fig. 2

Kinetic changes in neutralizing activity (PRNT₅₀) in recovered MERS patients who had pneumonia. (A) Kinetic changes in neutralizing activity (PRNT₅₀) in serum samples collected from recovered MERS patients who had pneumonia (G-II and G-III) are presented. G-II + G-III: left graph, G-II (green) or G-III (red): right graph. Box and whisker (min to max) plots, including the median value (solid line), are presented for each indicated time point (G-II: n = 10–23 and G-III: n = 9–16). For comparisons of values at the indicated time points, statistical analysis was performed using one-way ANOVA, followed by the Newman–Keuls t-test. ∗, p < 0.05. (B) Correlations of OD ratios against the S1 antigen with neutralizing antibody titres against MERS-CoV (PRNT₅₀) were assessed using linear regression analysis (black line) with 95% confidence intervals (gray) and the Pearson correlation test (coefficient and p value are presented). (C) Kinetic changes in OD ratios against the S1 antigen (blue) and neutralizing activity (PRNT₅₀, red) in serum samples collected from 19 recovered MERS patients without negative seroconversion during the study period. Linear regression analysis (solid line) with 95% confidence intervals (shaded cyan and orange represent OD ratios and neutralizing activity, respectively) was performed to calculate the half-life (OD ratio: 107 months and PRNT₅₀: 20 months).