Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.

Fig. 1. SARS-CoV-2 spike antibody titers in 30,082 individuals.

(A) The percentage of individuals with antibody titers of 1:80 (low), 1:160 (low), 1:320 (moderate), 1:960 (high), and ≥1:2880 (high). (B) Absolute numbers of individuals testing positive and percent of individuals with titers of 1:320 over time. Testing of each sample was performed once in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory using an assay that received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA).

Fig. 2. Neutralizing activity of serum samples in relation to ELISA titers.

(A) A correlation analysis between ELISA titers on the x axis and neutralization titers in a microneutralization assay on the y axis. The Spearman ρ was determined. Red bars indicate the geometric mean. (B) The proportion of sera that exert any neutralizing activity in each of the ELISA titer categories. Testing was performed once, using an FDA EUA ELISA in a CLIA laboratory, or twice, following a standardized neutralization protocol.

Fig. 3. Antibody titer stability over time.

(A) Titers of 121 volunteers whose blood was initially drawn ~30 days after COVID-19 symptom onset and who were then recalled for additional blood draws at ~82 days and 148 days after symptom onset. (B to F) The same data as in (A), but stratified by the initial (day 30) titer. Titers are graphed as geometric mean titers (GMT) with geometric standard error. (G) Neutralization titers of 36 individuals over time. A paired one-way analysis of variance corrected for multiple comparison was used to determine statistical significance. (H) A correlation analysis between ELISA titers on the x axis and neutralization titers in a microneutralization assay on the y axis at day 148. Red bars indicate the geometric mean. The Spearman ρ was determined. Testing was performed once, using an FDA EUA ELISA in a CLIA-certified laboratory, or twice, following a standardized neutralization protocol.