In a new study posted to the medRxiv* preprint server, researchers discussed the stability of spike antibody titers mounted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and their ability to protect from infection with other antigenically similar SARS-CoV-2 variants.

Background

According to the World health organization (WHO) statistics, over 486 million people have been infected with SARS-CoV-2, the organism that caused the coronavirus disease 2019 (COVID-19) pandemic.

Infection with SARS-CoV-2 leads to the development of adaptive immune responses, which in some patients remain active for a longer time, while in some fade quickly. These immune responses include either induction of SARS-CoV-2 spike-binding antibodies or neutralizing antibodies.

Usually, in any infection, the antibodies mounted are at a strong peak during the infection, followed by declining levels and then stabilization. This pattern of antibody level durability and protection in SARS-CoV-2 was investigated in the current study.

About the study

In the present research, two PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2) cohort studies involving a total of 501 healthcare workers with and without prior infection of SARS-CoV-2, enrolled between April 2020 and August 2021, were performed. The studies involved frequent and longitudinal sampling from two to six months up to 400 days post-infection.

For the protection dataset, 400 participants, including 273 females, 126 males, and one unknown gender, without any co-morbidities were identified. These unvaccinated participants were either monitored for four weeks of follow-up, or two study visits were performed. During the enrolment, 150 were seropositive, while 250 were seronegative for SARS-CoV-2 spike antibodies. A total of 2,106 study visits were carried out to determine the risk of infection and seroreversion in 400 participants.

For determining the antibody durability, 137 seropositive participants from 400 participants with known dates of COVID-19 positive tests or symptoms onset were selected, and a total of 813 distinct visits were conducted.

Eleven participants were detected with new SARS-CoV-2 infections, of which ten were naïve participants, and one was previously infected without detectable antibodies. Infection was confirmed for one individual by nucleic acid amplification test (NAAT) conducted by the study group, nine infections were confirmed outside the Mount Sinai Health System, while one infection was confirmed by seroconversion.

Antibody titers against the SARS-CoV-2 spike proteins were measured by a two-step enzyme-linked immunosorbent assay (ELISA). Firstly, the sera were screened for IgG at 11:50 dilution, and antibodies were detected against a full-length spike protein.

Further, the durability of antibodies and changes in their titers with time were determined using an additive mixed model mgcv package (version 1.8-36) for R (version 4.1.1). Participants with low levels of detectable antibodies (less than 1:80) were removed from the analysis, whereas those with detectable antibodies of 1:80-1:6,400 were used. In this analysis, sex, age, and baseline titers were included as covariates.

The frequency of seroreversion was determined by calculating the probability of survival via the Kaplan-Meier estimator. Seroreversion was defined by patients who were seropositive initially, however, subsequently, the titers went undetectable or below the detection limit on two consecutive visits.

The researchers further studied whether the antibody titers were able to protect against re-infection with a genetically similar SARS-CoV-2 variant. Participants with detectable antibodies were compared to those with undetectable antibodies by a Fisher’s exact test.

Study findings

The results demonstrated that spike binding IgG antibody titers were highly variable amongst the COVID-19 survivors, with titers ranging between 1:80 and 1:6,400. Around 59.1% of participants displayed antibody titers above 1:800 at the baseline visit.

It was found that after the infection, the antibody titers decreased over the first three months, after which the levels of antibodies were stabilized for a year. Moreover, participants with higher antibodies showed a higher initial decline than those with lower antibody levels.

The researchers also investigated whether age or sex has any effect on antibody durability. Participants of age 40 or over showed 1.62-fold higher antibody levels. Sex-wise, female participants displayed 1.40-fold higher antibody titers than male participants.

It was also observed that eight participants out of 137 who were initially seropositive (below 1:800) for the antibodies tested negative during follow-up study, confirming seroreversion.

Interestingly, the antibodies mounted upon infection were detectable after re-infection, demonstrating significant protection from the antigenically similar variants.

Conclusions

Overall, this current study reported the pattern of SARS-CoV-2 antibody durability over time, with an initial decline and then stabilization after three months. Seroreversion was found to be lower, and participants with ages over 40, as well as females, showed higher antibody levels. Moreover, the antibodies mounted in the infection showed protection towards re-infection with other variants.

However, this study had a few limitations. The enrolment done in the first wave relied on clinical symptoms and not on molecular tests. Moreover, a smaller sample size due to increased numbers of vaccinated healthcare workers may have led to bias in the study.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Prajakta Tambe

Prajakta Tambe, Ph.D. worked at Queen’s University Belfast on a project that focused on studying ‘Role of Tregs in Acute Respiratory Distress Syndrome'. Prajakta completed a Ph.D. in August 2020 at Agharkar Research Institute, University of Pune, India. Her work aimed to develop dendrimer-based nanoparticles for the targeted delivery of MCL-1 gene-specific siRNA to bring about apoptosis in breast and prostate cancer cells and in vivo breast cancer xenograft models.