Factors Associated with the Decay of Anti-SARS-CoV-2 Neutralizing Antibodies Among Recipients of an Adenoviral Vector-Based AZD1222 and a Whole-Virion Inactivated (BBV152) Vaccine in Chennai, India: a Cross-Sectional Cohort Study

Background: The SARS-CoV-2 has caused high rates of morbidity and mortality and is spreading globally, including in populations with high rates of vaccination. The magnitude of protection conferred after recovery from a natural infection or by vaccine administration, and the duration of protective immunity developed post-vaccination, remains ambiguous.Methods: We investigated the factors associated with antibody decay in 519 individuals who received treatment for COVID-19-related illness or received COVID-19 vaccination with two commercial vaccines, viz., an adenoviral vector-based (AZD1222) and a whole-virion-based inactivated (BBV152) vaccine at the State Public Health Laboratory, Directorate of Public Health and Preventive Medicine, and the Government Corona Hospital, Chennai, India from March 2021. The inclusion criteria were that the participants needed to be >18 years, and there were no exclusion criteria. The medical records of the participants were reviewed and data such as patient demography, comorbidities, history of SARS-CoV-2 infection, date and type of vaccine received were recorded. Blood samples were collected during regular follow up post infection/vaccination, and tested for their levels of anti-SARS-CoV-2 IgG. Blood collected were tested for their levels of anti-SARS-CoV-2 IgG by a commercial automated chemiluminescent immunoassay (CLIA). The 519 individuals recruited into the study were separated into two groups, i.e., “unvaccinated” (n=52) versus “vaccinated” (n=467). The “unvaccinated” group was further bifurcated into two sub-groups with those who did not have a history of natural infection of SARS-CoV-2 (n=25) and those who had a natural COVID-19 infection (n=27). The vaccinated group was also divided into two groups i.e., participants who received the AZD1222 (n=259) and those who received the BBV152 (n=208) vaccines. Of note, a small fraction of vaccinees had developed a natural infection prior to receiving vaccination (n=85); whilst another portion of the participants had developed a breakthrough infection ~14 days post-vaccination (n=149).Findings: Age and underlying comorbidities were the two variables that were independently associated with development of a breakthrough infection. Individuals who were >60 years of age with underlying comorbid conditions had a ~15 times and ~10 times greater risk for developing a breakthrough infection and hospitalization, respectively. The time elapsed since the first booster dose was associated with attrition in anti-SARS-CoV-2 IgG, where each month passed was associated with an ebb in the neutralizing antibody levels by a coefficient of -6 units. Participants who were >60 years had an accelerated IgG decay rate, that was associated with a decrease by 23 units as compared to those <60 years. Each month of lapse was associated with increased risk of contracting a breakthrough infection and hospitalization by 0.85 and 0.85, respectively.Interpretation: Our findings advocate that the elderly with underlying comorbidities represent a high-risk group warranting more medical attention, and measures to boost anti-SARS-CoV-2 immune responses such as administering a second booster dose with both the vaccines, viz., AZD1222 and BBV152 are urgently warranted.Funding Information: None to declare. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Human Ethics Committee of the Madras Medical College (EC No. 03092021).