Humoral and T-Cell Immune Response After 3 Doses of Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Fragile Patients: The Italian VAX4FRAIL Study
Paolo Corradini, Chiara Agrati, Giovanni Apolone, Alberto Mantovani, Diana Giannarelli, Vincenzo Marasco, Veronica Bordoni, Alessandra Sacchi, Giulia Matusali, Carlo Salvarani, Pier Luigi Zinzani, Renato Mantegazza, Fabrizio Tagliavini, Maria Teresa Lupo Stanghellini, Fabio Ciceri, Silvia Damian, Antonio Uccelli, Daniela Fenoglio, Nicola Silvestris, Fausto Baldanti, Giulia Piaggio, Gennaro Ciliberto, Aldo Morrone, Franco Locatelli, Valentina Sinno, Maria Rescigno, Massimo Costantini, VAX4FRAIL Study Group, Giovanni Apolone, Alberto Mantovani, Massimo Costantini, Nicola Silvestris, Chiara Agrati, Giovanni Apolone, Fabio Ciceri, Gennaro Ciliberto, Massimo Costantini, Franco Locatelli, Alberto Mantovani, Fausto Baldanti, Aldo Morrone, Angelo Paradiso, Carlo Salvarani, Nicola Silvestris, Fabrizio Tagliavini, Antonio Uccelli, Pier Luigi Zinzani, Paolo Corradini, Gennaro Ciliberto, Carlo Salvarani, Antonio Uccelli, Renato Mantegazza, Chiara Agrati, Maria Rescigno, Daniela Fenoglio, Roberta Mortarini, Cristina Tresoldi, Laura Conti, Chiara Mandoj, Michela Lizier, Stefania Croci, Fausto Baldanti, Vito Michele Garrisi, Fulvio Baggi, Tiziana Lazzarotto, Francesca Bonifazi, Fulvia Pimpinelli, Concetta Quintarelli, Rita Carsetti, Enrico Girardi, Aurora Bettini, Veronica Bordoni, Concetta Castilletti, Eleonora Cimini, Rita Casetti, Francesca Colavita, Flavia Cristofanelli, Massimo Francalancia, Simona Gili, Delia Goletti, Giulia Gramigna, Germana Grassi, Daniele Lapa, Sara Leone, Davide Mariotti, Giulia Matusali, Silvia Meschi, Stefania Notari, Enzo Puro, Marika Rubino, Alessandra Sacchi, Eleonora Tartaglia, Paolo Corradini, Silvia Damian, Vincenzo Marasco, Filippo de Braud, Maria Teresa Lupo Stanghellini, Lorenzo Dagna, Francesca Rita Ogliari, Massimo Filippi
Abstract
BACKGROUND: Patients with solid or hematological tumors or neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe coronavirus disease 2019 and an inadequate response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: We designed a prospective Italian multicenter study to assess humoral and T-cell responses to SARS-CoV-2 vaccination in patients (n = 378) with solid tumors (ST), hematological malignancies (HM), neurological disorders (ND), and immunorheumatological diseases (ID). A group of healthy controls was also included. We analyzed the immunogenicity of the primary vaccination schedule and booster dose. RESULTS: The overall seroconversion rate in patients after 2 doses was 62.1%. Significantly lower rates were observed in HM (52.4%) and ID (51.9%) than in ST (95.6%) and ND (70.7%); a lower median antibody level was detected in HM and ID versus ST and ND (P < .0001). Similar rates of patients with a positive SARS-CoV-2 T-cell response were found in all disease groups, with a higher level observed in ND. The booster dose improved the humoral response in all disease groups, although to a lesser extent in HM patients, whereas the T-cell response increased similarly in all groups. In the multivariable logistic model, independent predictors of seroconversion were disease subgroup, treatment type, and age. Ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (P < .0001) but had no effect on T-cell responses. CONCLUSIONS: Immunosuppressive treatment more than disease type per se is a risk factor for a low humoral response after vaccination. The booster dose can improve both humoral and T-cell responses.