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

Our take —

The degree of immunity acquired by individuals after SARS-CoV-2 infection, and how it changes over time, is a matter of considerable public health concern. In contrast to a previous study showing rapidly waning levels of antibodies that target a different SARS-CoV-2 antigen among patients with mild symptoms, this study from New York City shows that neutralizing antibodies to SARS-CoV-2 spike protein diminished over time but remained at high levels up to 3 months after symptom onset in a group of patients with mostly mild illness. The patient population was small and not well described, so it is unclear if these results apply to the broader population of those infected with SARS-CoV-2. Important questions remain about how varying levels of SARS-CoV-2 antibody translate to protection from infection.

Study design

Case series; prospective cohort; other

Study population and setting

This paper reports on three related studies: 1) Enzyme linked immunoassay (ELISA) testing for IgG antibodies to the SARS-CoV-2 spike protein among 72,401 individuals with laboratory-confirmed or suspected infection approximately 30 days after symptom onset from the Mount Sinai Health System in New York City, from March to October 6, 2020; 2) testing of 120 samples that had a known ELISA titer for neutralization of SARS-CoV-2 using a quantitative neutralization assay; and 3) longitudinal screening of 121 patients for IgG antibodies to the SARS-CoV-2 spike protein at two additional time points (approximately 82 and 148 days after symptom onset) after the initial screening (approximately 30 days after symptom onset).

Summary of Main Findings

Less than 5% of all individuals screened required hospitalization or emergency room evaluation. Of those screened, 30,082 (42%) tested positive for detectable antibodies to the SARS-CoV-2 spike protein at a titer of 1:80 or higher. Most of those testing positive had moderate-to-high titers (defined as 1:320 or higher): 2.3% had a titer of 1:80, 4.8% of 1:160, 22.5% of 1:320, 31.8% of 1:960, and 38.6% of 1:2880. Neutralizing titers significantly correlated with ELISA titers (Spearman’s r=0.87). Half of sera with spike-binding titers between 1:80 and 1:160 had neutralizing activity, while 90% of sera with 1:320 titers and all those with 1:960 titers or above had neutralizing activity. Among the 121 individuals sampled over a total of three time points (at an average of 30, 82, and 148 days post-symptom onset), the geometric mean titers (GMT) declined from 764 to 690 to 404. Among those with a 1:320 titer or lower, antibody titers increased on average at the second time point, followed by a decrease at the third time point. Three individuals with initially low titers (1:80) lost reactivity, one at the second time point and two at the third. The correlation between neutralizing and ELISA titers remained high at the third time point (r=0.79).

Study Strengths

This study examined antibodies to the spike protein of SARS-CoV-2, which are likely to be more relevant to immunity than antibodies to nucleoprotein. Antibody titers were measured in a large number of individuals using an assay with high accuracy in a validation panel. Longitudinal analyses of antibody titers considered two time points after the initial assay, allowing for discernment of nonlinearities in trajectory.

Limitations

Patient demographic and clinical characteristics were not reported, which makes it difficult to interpret how these data apply to any particular group of individuals. Of particular concern is the lack of data on COVID-19 clinical severity in either the larger study population or in the two substudies. Thus, while it appears that these studies were conducted on primarily mild cases of COVID-19, this study did not assess any relationship between disease severity and antibody response. Also, the timing of initial antibody screening relative to symptom onset or date of potential exposure was not characterized in the larger study population and there was variation in the timing of antibody assays in the longitudinal study. Not all individuals screened for antibodies were tested for SARS-CoV-2 infection, which means an unknown number of people who had been infected with SARS-CoV-2 may have tested negative for antibodies. The size of the population in the longitudinal study (n=121) and the lack of reported demographic or clinical characteristics makes it difficult to generalize the results.

Value added

This study provides some of the strongest evidence to date regarding the persistence of neutralizing antibodies to SARS-CoV-2 over time, particularly among those without severe disease. This has implications for both pandemic planning and vaccine development.

This review was posted on: 2 November 2020