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
Authors: Corradini Paolo , Agrati Chiara , Apolone Giovanni , Mantovani Alberto , Giannarelli Diana , Marasco Vincenzo , Bordoni Veronica , Sacchi Alessandra , Matusali Giulia , Salvarani Carlo , Zinzani Pier Luigi , Mantegazza Renato , Tagliavini Fabrizio , Lupo-Stanghellini Maria Teresa , Ciceri Fabio , Damian Silvia , Uccelli Antonio , Fenoglio Daniela , Silvestris Nicola , Baldanti Fausto , Piaggio Giulia , Ciliberto Gennaro , Morrone Aldo , Locatelli Franco , Sinno Valentina , Rescigno Maria , Costantini Massimo ,   VAX4FRAIL Study Group, Apolone Giovanni , Mantovani Alberto , Costantini Massimo , Silvestris Nicola , Agrati Chiara , Apolone Giovanni , Ciceri Fabio , Ciliberto Gennaro , Costantini Massimo , Locatelli Franco , Mantovani Alberto , Baldanti Fausto , Morrone Aldo , Paradiso Angelo , Salvarani Carlo , Silvestris Nicola , Tagliavini Fabrizio , Uccelli Antonio , Zinzani Pier Luigi , Corradini Paolo , Ciliberto Gennaro , Salvarani Carlo , Uccelli Antonio , Mantegazza Renato , Agrati Chiara , Rescigno Maria , Fenoglio Daniela , Mortarini Roberta , Tresoldi Cristina , Conti Laura , Mandoj Chiara , Lizier Michela , Croci Stefania , Baldanti Fausto , Garrisi Vito , Baggi Fulvio , Lazzarotto Tiziana , Bonifazi Francesca , Pimpinelli Fulvia , Quintarelli Concetta , Carsetti Rita , Girardi Enrico , Bettini Aurora , Bordoni Veronica , Castilletti Concetta , Cimini Eleonora , Casetti Rita , Colavita Francesca , Cristofanelli Flavia , Francalancia Massimo , Gili Simona , Goletti Delia , Gramigna Giulia , Grassi Germana , Lapa Daniele , Leone Sara , Mariotti Davide , Matusali Giulia , Meschi Silvia , Notari Stefania , Puro Enzo , Rubino Marika , Sacchi Alessandra , Tartaglia Eleonora , Corradini Paolo , Damian Silvia , Marasco Vincenzo , de Braud Filippo , Stanghellini Maria Teresa Lupo , Dagna Lorenzo , Ogliari Francesca , Filippi Massimo , Bruno Alessandro , Catalano Gloria , Nitti Rosamaria , Mengarelli Andrea , Marchesi Francesco , e Gabriele Minuti Giancarlo Paoletti , Papa Elena , Azzolini Elena , Germagnoli Luca , Selmi Carlo , De Santis Maria , Carlo-Stella Carmelo , Bertuzzi Alexia , Motta Francesca , Ceribelli Angela , Miggiano Chiara , Fornasa Giulia , Baldanti Fausto , Monti Sara , Montecucco Carlo Maurizio , Morrone Aldo , Graceffa Dario , Catanoso Maria Grazia , Guberti Monica , Pinto Carmine , Merli Francesco , Valzania Franco , Divella Rosa , Tufaro Antonio , Garrisi Vito , Delcuratolo Sabina , Miano Mariana , Uccelli Antonio , Pronzato Paolo , Inglese Matilde , Genova Carlo , Lapucci Caterina , Laroni Alice , Poirè Ilaria , Fusconi Marco , Stefoni Vittorio , Pantaleo Maria Abbondanza , Giannarelli Diana , Sinno Valentina , Di Cosimo Serena , Turola Elena , Pulice Iolanda , Trinca Stefania , Piaggio Giulia , Pozzi Chiara , Cassaniti Irene , Barberini Alessandro , Belvedere Arianna , Delcuratolo Sabina , Elena Rinaldi , Bortone Federica , Dal Bello Maria Giovanna , Corazza Silvia 
Published: May 2022

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 &lt; .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 &lt; .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.