Antibody titers against SARS-CoV-2 decline, but do not disappear for several months

Abstract

Background: To develop an effective vaccine against a novel viral pathogen, it is important to understand the longitudinal antibody responses against its first infection. Here we performed a longitudinal study of antibody responses against SARS-CoV-2 in symptomatic patients.

Methods: Sequential blood samples were collected from 39 individuals at various timepoints between 0 and 154 days after onset. IgG or IgM titers to the receptor binding domain (RBD) of the S protein, the ectodomain of the S protein, and the N protein were determined by using an ELISA. Neutralizing antibody titers were measured by using a plaque reduction assay.

Findings: The IgG titers to the RBD of the S protein, the ectodomain of the S protein, and the N protein peaked at about 20 days after onset, gradually decreased thereafter, and were maintained for several months after onset. Extrapolation modeling analysis suggested that the IgG antibodies were maintained for this amount of time because the rate of reduction slowed after 30 days post-onset. IgM titers to the RBD decreased rapidly and disappeared in some individuals after 90 days post-onset. All patients, except one, possessed neutralizing antibodies against authentic SARS-CoV-2, which they retained at 90 days after onset. The highest antibody titers in patients with severe infections were higher than those in patients with mild or moderate infections, but the decrease in antibody titer in the severe infection cohort was more remarkable than that in the mild or moderate infection cohort.

Interpretation: Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection.

Funding: The Japan Agency for Medical Research and Development and the National Institutes of Allergy and Infectious Diseases.

Fig. 1

Longitudinal change in antibody titers of 39 COVID-19 patients. Blood samples were obtained from 39 COVID-19 patients at several timepoints between 0 and 154 days after onset. IgG titers against the RBD (A), the ectodomain of the S protein (C), and the N protein (D); IgM titers against the RBD (B); and neutralization titers (E) were determined by performing an ELISA and a neutralization test using a wild-type virus. The maximum dilution of blood samples that gave a positive result in the ELISA or reduced the plaque number by more than 50% was selected as the ELISA or neutralization titer. Lines of the same color indicate data from the same patient. (F) Geometric mean antibody titers at the highest titer over the entire study period (black) and at least 60 days post-onset (gray). **, p<0.01 (paired t-test).

Fig. 2

Modeling the longitudinal response in 39 patients. The gray area indicates the 95% high density interval of the posterior distribution from the hierarchical model across all patients. The red line indicates the median level in the posterior distribution. Jitter in the y-dimension has been added to aid visualization of the data points.

Fig. 3

Changes in antibody titers of patients with mild, moderate, or severe infections. The changes in antibody titers against the RBD, ectodomain, and N protein shown in Fig. 1 were divided into three groups (mild, moderate, and severe) according to disease severity. Lines of the same color in each group indicate data from the same patient.

Fig. 4

Geometric mean highest antibody titers over the entire study period and after 60 days post-onset. The geometric mean titers of RBD IgG, RBD IgM, ectodomain, N proteins, and neutralization in the mild, moderate, and severe groups at the highest titers over the entire study period (black squares) and after 60 days post-onset (gray squares) were calculated. * and **, p<0.05 and p<0.01, respectively (one-way ANOVA followed by Tukey's test).