Clinical Variables Correlate With Serum Neutralizing Antibody Titers After COVID-19 mRNA Vaccination in an Adult, US-Based Population

Background: We studied whether comorbid conditions impact strength and duration of immune responses after SARS-CoV-2 mRNA vaccination in a US-based, adult population.Methods: Sera (pre-and-post-BNT162b2 vaccination) were tested serially up to 6 months after two doses of vaccine for SARS-CoV-2-anti-Spike neutralizing capacity by pseudotyping assay in 91 Veterans and 33 healthcare workers; neutralizing titers were correlated to clinical variables with multivariate regression. In 36 participants, post-booster effect was measured. Findings: After completion of primary vaccine series, neutralizing antibody IC-50 titers were high at one month (14-fold increase from pre-vaccination), declined at six months (3·3-fold increase), and increased at one month post-booster (52.5-fold increase). Age >65 years (β=-0·94, p=0·001) and malignancy (β=-0·88, p=0·002) significantly reduced strength of response at 1 month. Both strength and durability of response at 6 months, respectively, were negatively impacted by end-stage renal disease [(β=-1·10, p=0·004); (β=-0·66, p=0·014)], diabetes mellitus [(β=-0·57, p=0·032); (β=-0·44, p=0·028)], and systemic steroid use [(β=-0·066, p=0·032); (β=-0·55, p=0·037)]. The booster response was unaffected by clinical factors.Interpretation: Multiple clinical factors impacted the strength and duration of post-vaccination serum neutralizing antibodies in this adult population. Response to booster dose was universally robust, however. This suggests a post-vaccination sustained and effective anti-Spike memory immune response. Funding Information: Funding for this study was provided by National Institutes of Health (awards R01 AI150334 to RES, and T32AI007517 to BI). Statistical analysis was supported by Global Health Equity Scholars (FIC D43TW010540 to RS), the NIH (5T32AI007517-20 to LP) and the Yale School of Medicine Medical Student Research Fellowship (AHS).Declaration of Interests: The authors declare no conflict of interests.Ethics Approval Statement: The study was approved by the Institutional Review Board at the VACHS. Written informed consent was obtained from each participant.