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      Humoral and T-cell immune response after three doses of mRNA SARS-CoV-2 vaccines in fragile patients: the Italian VAX4FRAIL study

      research-article
      1 , 2 , 3 , , 4 , 5 , 6 , 7 , 8 , 1 , 2 , 3 , 3 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 1 , 18 , 19 , 19 , 20 , 21 , 22 , 23 , 24 ,   25 , 26 , 27 , 28 , 29 , 1 , 6 , 30 , 31 , the VAX4FRAIL Study Group
      Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
      Oxford University Press
      Fragile patients, SARS-CoV-2 mRNA vaccine, humoral immunity, T-cell immunity

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          Abstract

          Background

          Patients with solid or hematological tumors, neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe COVID-19 and an inadequate response to SARS-CoV-2 vaccination.

          Methods

          We designed a prospective Italian multicentrer 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 < 0.0001). 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, while 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 < 0.0001) 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.

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          Author and article information

          Journal
          Clin Infect Dis
          Clin Infect Dis
          cid
          Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
          Oxford University Press
          1058-4838
          1537-6591
          24 May 2022
          24 May 2022
          : ciac404
          Affiliations
          [1 ]Department of Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , Italy
          [2 ] School of Medicine, University of Milan , Italy
          [3 ]Cellular Immunology Laboratory, National Institute for Infectious Diseases L Spallanzani – IRCCS , Rome, Italy
          [4 ] Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano , Italy
          [5 ] Humanitas Scientific Directorate, IRCCS Humanitas, Clinical and Research Center , Rozzano, Italy
          [6 ]Department of Biomedical Sciences, Humanitas University , Milan, Italy
          [7 ] William Harvey Research Institute, Queen Mary University , London, United Kingdom
          [8 ]Biostatistical Unit, Istituto Nazionale Tumori Regina Elena IRCCS - IFO , Rome, Italy
          [9 ]Virology Laboratory, National Institute for Infectious Diseases L Spallanzani – IRCCS , Rome, Italy
          [10 ] Unità di Reumatologia, Azienda USL-IRCCS , Reggio Emilia, Italy
          [11 ] Unità di Reumatologia, Università degli Studi di Modena e Reggio Emilia , Modena
          [12 ] Istituto di Ematologia “Seràgnoli”, Azienda Ospedaliero-Universitaria di Bologna - IRCCS , Bologna, Italy
          [13 ] Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna , Bologna, Italy
          [14 ] Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta , Milano, Italy
          [15 ] Fondazione IRCCS Istituto Neurologico Carlo Besta , Milan, Italy
          [16 ] Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute , Milano, Italy
          [17 ] Scientific Directorate, IRCSS San Raffaele Scientific Institute , Milano, Italy
          [18 ]Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR), University of Genoa , Genoa, Italy
          [19 ]Biotherapy Unit, IRCCS Ospedale Policlinico San Martino , 16132 Genoa, Italy
          [20 ] Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa , Italy
          [21 ]Medical Oncology Department, IRCCS Istituto Tumori “Giovanni Paolo II” , Bari, Italy
          [22 ]Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro” , Bari, Italy
          [23 ]Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo
          [24 ]Department of Clinical, Surgical, Diagnostics and Pediatric Sciences, University of Pavia , Pavia, Italy
          [25 ] SAFU Unit IRCCS Regina Elena, National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO) , Rome, Italy
          [26 ] Scientific Directorate IRCCS Regina Elena, National Cancer Institute, Istituti Fisioterapici Ospitalieri (IFO) , Rome, Italy
          [27 ]Scientific Directorate, San Gallicano Dermatological Institute IRCCS , Rome, Italy
          [28 ]Department of Pediatric Hematology and Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù
          [29 ]Department of Gynecology-Obstetrics and Pediatrics, University “La Sapienza” , Roma, Italy
          [30 ]Mucosal Immunology and Microbiota Unit, IRCCS Humanitas Clinical and Research Center , Milano, Italy
          [31 ]Scientific Directorate, Azienda Unità Sanitaria Locale (USL)-IRCCS Reggio Emilia , Reggio Emilia, Italy
          Author notes
          Corresponding author: Chiara Agrati, PhD Head, Cellular Immunology Laboratory INMI L Spallanzani, Via Portuense 292, 00149, Rome, Italy E-mail: chiara.agrati@ 123456inmi.it
          [*]

          Equal contribution as first author

          [#]

          Equal contribution as last author

          [**]

          VAX4FRAIL Study Group members are listed in the Acknowledgments section.

          Author information
          https://orcid.org/0000-0002-5252-0927
          Article
          ciac404
          10.1093/cid/ciac404
          9213871
          35607769
          dc7a995a-5237-4e71-b2ee-b7a7f481cd61
          © The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

          History
          : 31 December 2021
          : 09 May 2022
          : 18 May 2022
          Page count
          Pages: 35
          Categories
          Major Article
          AcademicSubjects/MED00290
          Custom metadata
          accepted-manuscript
          PAP

          Infectious disease & Microbiology
          fragile patients,sars-cov-2 mrna vaccine,humoral immunity,t-cell immunity

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