Viruses (Nov 2022)

Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers—ORCHESTRA Project

  • Giulia Collatuzzo,
  • Vittorio Lodi,
  • Daniela Feola,
  • Giuseppe De Palma,
  • Emanuele Sansone,
  • Emma Sala,
  • Christian Janke,
  • Noemi Castelletti,
  • Stefano Porru,
  • Gianluca Spiteri,
  • Maria Grazia Lourdes Monaco,
  • Francesca Larese Filon,
  • Corrado Negro,
  • Luca Cegolon,
  • Jana Beresova,
  • Eleonora Fabianova,
  • Lucia A. Carrasco-Ribelles,
  • Pere Toràn-Monserrat,
  • Marta Maria Rodriguez-Suarez,
  • Guillermo Fernandez-Tardon,
  • Shuffield S. Asafo,
  • Giorgia Ditano,
  • Mahsa Abedini,
  • Paolo Boffetta

Journal volume & issue
Vol. 14, no. 12
p. 2657


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Background: The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months’ serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86–0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97–0.98), previous infection (3.03, 95% CI = 2.92–3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09–1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39–1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44–0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12–1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1–7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.