Antibody Responses to COVID-19 Vaccine Dwindling Over Age in the Elderly Population: A Phase 4 Trial-Seroepidemiology

Background: The COVID-19 has been pandemic for three years which causes more severe cases and deaths in the elderly. Its vaccine helps reduce its impact, especially reducing severe cases and deaths, on them. The elderly have been hesitating to get the COVID-19 vaccine. We investigated antibody responses to inactivated SARS-CoV-2 vaccine in an elderly population. Methods: We conducted a phase 4 trial, i.e., a post-market sero-epidemiology. We recruited 4,632 participants aged from 50 to 102 years after vaccination and collected data of serum SARS-CoV-2-specific total antibody (TAb) and correlates. STATA 15 was used to analyze data. Primary outcome was the TAb geometric mean titer (GMT) and secondary outcome was the TAb dwindling over age. Univariate, bivariate and multivariate regressions and stratifications were used to examine the associations of the TAb GMT with age and trend analyses were used to test whether the TAb dwindling over age was significant. Findings: All participants had a detectable TAb that was overall at a low level cross all age groups. The TAb GMT (95% CI) in AU/mL was 3·05 (2·93, 3·18) (its corresponding arithmetic mean (95% CI) was 17·77 (16·13, 19·42)) in all participants and 4·33 (3·88, 4·84), 3·86 (3·49, 4·28), 3·24 (2·92, 3·59), 2·77 (2·60, 2·96), and 2·65 (2·48, 2·83) in the age group of 50-54, 55-59, 60-64, 65-74, and 75 years or older, respectively. The TAb GMT was dwindling over age with a significant trend (P < 0·001), and this trend remained consistently significant after adjusting for confounders and modifiers and in each subgroup of gender, the status of hypertension, and or diabetes, respectively. The TAb GMT was significantly lower in those with hypertension, or diabetes or either compared to those with neither. Interpretation: Inactivated SARS-CoV-2 vaccine is effective to seniors. This is the first study to have found an inverse dose-response relationship between the TAb and age though the response is overall at the low level cross all age groups. Seniors, especially with chronic diseases, should get the COVID-19 vaccine and their vaccination frequency, dose, and method may need to be different from the young population aged in order to increase the SARS-CoV-2-specific total antibody titer.Funding: This study was supported by the Red Cross Society of China in Quzhou city which donated an automated Chemiluminescence Immunoassay System NMPA Wan200+ that was used to measure the SARS-CoV-2-specific TAb titer and by the Zhejiang Chinese Medical University Affiliated Hospital Special Science & Technology Fund (Grant No.: 2021FSYYZZ11) which partially supported the expenses for data cleaning and validationDeclaration of Interest: All authors declare no competing interests with any individuals or organizaEthical Approval: This study was approved (Approval NO: 2022-02-030) by the Ethics Committee of Quzhou Hospital of Traditional Chinese Medicine (TCM)—Zhejiang Chinese Medical University Affiliated Four-Province- Bordering Hospit