Relationship Between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort
Authors: Bonazzetti Cecilia , Tazza Beatrice , Gibertoni Dino , Pasquini Zeno , Caroccia Natascia , Fanì Francesca , Fornaro Giacomo , Pascale Renato , Rinaldi Matteo , Miani Beatrice , Gamberini Chiara , Morelli Maria Cristina , Tamé Mariarosa , Busutti Marco , Comai Giorgia , Potena Luciano , Borgese Laura , Salvaterra Elena , Lazzarotto Tiziana , Scudeller Luigia , Viale Pierluigi , Giannella Maddalena ,   the CONTRAST Study Group, Di Chiara Michela , Giacomini Maria Eugenia , Vatamanu Oana , Marconi Lorenzo , Horna Clara Solera , Campoli Caterina , Bartoletti Michele , Bussini Linda , Trapani Fabio , Attard Luciano , Gatti Milo , Gramegna Antonio , La Manna Gaetano , Grandinetti Valeria , Demetri Marcello , Barbuto Simona , Abenavoli Chiara , Vitale Giovanni , Turco Laura , Ravaioli Matteo , Cescon Matteo , Bertuzzo Valentina , Messina Paola , Trombi Alessandra , Masetti Marco , Prestinenzi Paola , Sabatino Mario , Giovannini Laura , Alessio Aloisio , Russo Antonio , Scuppa Maria Francesca , Dolci Giampiero , Paganelli Gianmaria , Gabrielli Liliana , Pavoni Matteo , Leone Marta , Lanna Federica 
Published: January 2023

Abstract

Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed.

Methods
Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 – January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels.

Results
614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non–high-level AbR, younger age, and shorter time from transplant.

Conclusions
SOT patients with non–high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI.