In a recent study posted to the medRxiv* preprint server, researchers assessed the changes in the immunoglobulin (Ig) titers against the receptor-binding domain (RBD) of the spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) post-vaccination and natural SARS-CoV-2 infection in healthcare workers (HCW) of Boston.

Previous studies have reported the durability of anti-SARS-CoV-2 antibodies up to six months post-vaccination. However, the serological trends beyond six months of vaccination in individuals with and without coronavirus disease 2019 (COVID-19) history and its correlation with the extent of immune protection are unknown.

About the study

In the present study, researchers conducted a questionnaire survey-based analysis to determine the durability of vaccine-induced and prior COVID-19-induced changes in antibody titers over 15 months among HCWs of Boston’s Medical Center (BMC).

The study commenced in July 2020, and follow-ups were conducted in December 2020, March 2021, June 2021, and September 2021. Participants were classified into different groups based on the COVID-19 history and vaccination status, including subjects with COVID-19 history before vaccination, those with COVID-19 history post-vaccination, vaccinated without COVID-19 history, unvaccinated without COVID-19 history, and unvaccinated with COVID-19 history.

A total of 527 HCWs provided data on their comorbidities, reverse-transcription-polymerase chain reaction (RT-PCR) reports, and symptoms three months before the study. The self-reported RT-PCR reports and vaccination status were confirmed by electronic medical records (EMR). Serum was obtained at the beginning and the end of the study. The serum anti-S RBD IgG, anti-nucleocapsid IgG, and anti-S IgM titers were evaluated every three months.

Results

Most of the HCWs were women (77%) and worked as physicians (32%) or nurses (41%). The titers of the unvaccinated HCWs without COVID-19 history remained below the threshold of seropositivity and were lost on follow-up evaluations in June 2021. The unvaccinated subjects with COVID-19 history demonstrated anti-S IgG fluctuations that corresponded to the dates of SARS-CoV-2 infections.  

In July 2020, the mean titers for HCWs with COVID-19 before being vaccinated was 233 AU/mL, which increased by December 2020 to 375 AU/mL and remarkably increased further by March 2021 to 25,535 AU/mL, corresponding to the major vaccine uptakes. Between March and June 2021, the titers decreased to 8,342 AU/mL, followed by a further diminution to 4,463 AU/mL by September 2021, with an overall 83% seropositivity decline.

For most HCWs, the titers persisted above the seropositivity threshold for anti-S RBD IgG for a minimum of nine months post-vaccination, irrespective of infection history. Interestingly, HCWs with COVID-19 history before being vaccinated had substantially higher mean antibody titers on every follow-up compared to those without COVID-19.

Most vaccinated HCWs without COVID-19 history demonstrated peak titers (10,012 AU/mL) during March 2021, corresponding to major vaccine uptakes. However, the titers decreased by June 2021 to 2,406 AU/mL and further decreased to 999 AU/mL with an overall decrease of 90%. The subjects with COVID-19 history before being fully vaccinated had substantially altered mean titers of 25,112 AU/mL compared to those vaccinated without COVID-19 history (10,083 AU/mL).

Twelve subjects selected for an ongoing trial of Pfizer-BioNTech vaccination were vaccinated between August 2020 and September 2020. In these participants, titers of 4,685 AU/mL were detected in the December 2020 follow-up. However, by September 2021, 11 months post-vaccination, the titers declined to 370 AU/mL with an overall 92% decrease.

During March 2021, the titers for HCWs with COVID-19 history post minimum one vaccination increased to 8,446 AU/mL but declined by June 2021 to 1,812 AU/mL and further decreased by September 2021 to 989 AU/mL with an overall 88% decrease.

Eight of the 11 participants with breakthrough infections were SARS-CoV-2 positive during the vaccination period. There were three true breakthrough COVID-19 cases, with varying titers and symptoms (between 1,038 and 8,626 AU/mL). Interestingly, respondents with the least titers reported the most symptoms (runny nose, dyspnea, cough, and headache). This indicates that the severity of symptoms in breakthrough cases could be correlated with the serum titers. Additionally, an overall breakthrough case rate of 0.9% in the HCWs, all of whom had mild COVID-19, is indicative of vaccine efficacy.

Conclusion

To summarize, although the anti-S IgG titers persisted above the seropositivity threshold for 11 months after vaccination and 15 months after infection, they variably declined in patients differing in their vaccination status and history of SARS-CoV-2 infections. Notably, the titers were highest among HCWs with COVID-19 history before vaccination.

*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

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.