National Project on Vaccines, COVID-19 and Frail Patients (VAX4FRAIL)

A National, Multicentric, Observational, Prospective Study to Assess Immune Response to COVID-19 Vaccine in Frail Patients (VAX4FRAIL).

This is a multicentre observational study with the aim of evaluating the antibody and cellular response after vaccination for SARS-CoV-2 with Pfizer-BioNTech or Moderna vaccines in frail subjects with impaired immuno-competence, due to their underlying diseases or ongoing therapies.

Study Overview

• Status: Completed
• Conditions: COVID-19; Hematologic Diseases; Rheumatic Diseases; Solid Tumor; Neurologic Disorder
• Intervention / Treatment: Biological: COVID-19 vaccines

Detailed Description

The immune response to COVID-19 vaccination will be assessed at the following time points:

T0: the day of vaccination T1: the day of the booster dose according to the schedule of the two vaccines (Pfizer/BioNTech or Moderna) T2: between 5 and 7 weeks after T0 for those vaccinated with Pfizer/BioNTech and between 6 and 8 weeks after T0 for those vaccinated with Moderna.

• T3: 12 (± 1) weeks after T0
• T4: 24 (± 2) weeks from T0
• T5: 52 (± 2) weeks from T0 Prevention of SARS-CoV-2 infection will be assessed in terms of incidence of SARS-CoV-2 infections (NF molecular swab positive), and of SARS-CoV-2 infections requiring hospitalisation.

• Study Type: Observational
• Enrollment (Actual): 747

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy
    • IRCCS Istituto Tumori Giovanni Paolo II
  • Genova, Italy
    • Ospedale Policlinico San Martino IRCCS
  • Milano, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy
    • Irccs Ospedale San Raffaele
  • Milano, Italy
    • Foindazione IRCCS Istituto Neurologico Carlo Besta
  • Milano, Italy
    • IRCCS Istituto Clinico Humanitas
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
  • Reggio Emilia, Italy, 42123
    • Azienda USL IRCCS Di Reggio Emilia
  • Roma, Italy
    • IRCCS Istituto Nazionale Tumori Regina Elena
  • Roma, Italy
    • IRCCS Istituto per le Malattie Infettive Lazzaro Spallanzani
  • Roma, Italy
    • Istituto Dermatologico San Gallicano
  • Bologhna
    • Bologna, Bologhna, Italy
      • IRCCS Azienda Ospedaliera Universitaria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any subject undergoing SARS-CoV-2 vaccination can be enrolled in the study if included in at least one of the below subgroups due to the proper underlying conditions:

HEMATOLOGICAL MALIGNANCIES These subgroups have been decided considering that patients with hematological malignancies have a low immune response because of the lympholytic treatment they receive.

SOLID TUMORS (2). ANCA-associated vasculitis Interstitial lung disease (ILD) is a feature of many connective tissue diseases (CTDs), including systemic sclerosis, mixed connective tissue disease, systemic lupus erythematosus, and Sjogren syndrome, of dermatomyositis and polymyositis, and of rheumatoid arthritis.

Multiple sclerosis

Generalized Myasthenia Gravis Patients with myasthenia gravis

Description

Inclusion Criteria:

• Any subject undergoing SARS-CoV-2 vaccination with Pfizer-BioNTech or Moderna vaccines may be included in the study if they belong to at least one of the subgroups listed below:

  1. Hematological tumors
  2. Solid tumors
  3. Rheumatological diseases
  4. Neurological diseases

Exclusion Criteria:

• NA

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HEMATOLOGICAL MALIGNANCIES; 1a. Newly diagnosed patients with ANY haematological malignancy requiring treatment (No.=100). 1b. Patients with ongoing treatments or with treatments completed within 6 months (chemotherapy and target therapies) other than antibodies. More specifically: patients with ongoing or completed chemotherapy (No.=50) or patients with ongoing or completed Ibrutinib (No.=50) or patients with ongoing or completed ruxolitinib (No.=50) 1c. Patients treated with anti-CD19 or CD20 or CD22 or CD30 or anti-PD1 antibodies with or without chemotherapy OR patients receiving CAR-T cells: patients treated anti-B-cell (No.=50) or patients treated anti-CD30 (No.=50) or patients treated anti-PD1 (No.=50). 1d. Patients at three months after autologous or allogeneic transplantation without active immune suppressive therapy: after autologous transplantation (No.=50) or after allogenic transplantation (No.=50).	Biological: COVID-19 vaccines; This is an observational prospective study whose general objective is to assess the impact of COVID-19 vaccination in terms of induction of humoral and cell-mediated immune responses in selected fragile (altered immunocompetence) populations.
SOLID TUMORS; 2a. Chemotherapy in adjuvant therapy. All patients with a diagnosis of solid tumors apart resected basal-cell or squamous-cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, and carcinoma in situ of the Breast. Under curative surgery (stage II-III) for the solid tumor or hemotherapy alone or in combination with target therapies or radiotherapy (No.=100). 2b. Chemotherapy in metastatic Disease. All patients with a diagnosis of solid tumors with Metastatic disease (stage IV), undergoing chemotherapy alone or in combination with immunotherapy or target therapy (No.=100). 2c. Immunotherapy in metastatic Disease. All patients with a diagnosis of solid tumors with Metastatic disease (stage IV), undergoing immunotherapy alone (No.=100). 2d. Target therapies in metastatic Disease. All patients with a diagnosis of solid tumors with Metastatic disease (stage IV), Undergoing target therapy alone (No.=100)	Biological: COVID-19 vaccines; This is an observational prospective study whose general objective is to assess the impact of COVID-19 vaccination in terms of induction of humoral and cell-mediated immune responses in selected fragile (altered immunocompetence) populations.
IMMUNORHEUMATOLOGICAL DISEASES; 3a. Patients with ANCA-associated vasculitis classified according to Chapel Hill Consensus Conference nomenclature, treated with immunodepressants agents with/without glucocorticoids (No.=50) or treated with RTX with/without glucocorticoids (No.=50) 3b. Interstitial Lung Disease in Autoimmune Conditions. Patients with a diagnosis of a specific CTD, myositis or rheumatoid arthritis based on validated classification criteria, and clinically significant ILD defined as disease treated with traditional immunodepressants or rituximab and fibrotic and/or inflammatory changes on chest CT not attributable to infection, and no evidence of obstructive lung disease. Patients treated with traditional immunodepressive agents with/without glucocorticoidspatients (No.=50) or patients treated with rituximab with/without glucocorticoids (No.=50)	Biological: COVID-19 vaccines; This is an observational prospective study whose general objective is to assess the impact of COVID-19 vaccination in terms of induction of humoral and cell-mediated immune responses in selected fragile (altered immunocompetence) populations.
NEUROLOGICAL DISEASES; 4a. Patients with a diagnosis of multiple sclerosis, age < 60 years with relapsing-remitting MS on Ocrelizumab (anti-CD20 monoclonal antibody) (No.=50) or with secondary/primary progressive MS on Ocrelizumab (anti-CD20 monoclonal antibody) (No.=50). 4b. Generalized Myasthenia Gravis, on immunosuppressive polytherapies or on B-cell targeted biological treatments, with lymphocytes count < 1 cell/microliter, or with thymoma (No.=100)	Biological: COVID-19 vaccines; This is an observational prospective study whose general objective is to assess the impact of COVID-19 vaccination in terms of induction of humoral and cell-mediated immune responses in selected fragile (altered immunocompetence) populations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 vaccine immunization	For assessing the immunologic response to the COVID-19 vaccination, the anti-S antibodies levels in the fragile population will be quantified at T2 and compared with the anti-S antibodies levels quantified at the same time point in a population of healthy subjects.	5-7 weeks after T0 for Pfizer/BioNTech vaccination; 6-8 weeks after T0 for Moderna vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anti-S antibodies immunological response	for each time point, the anti-S antibodies levels will be quantified and compared with the anti-S antibodies levels quantified at the same time point in a population of healthy subjects (see controls).	at 6 times points T0 before vaccine administration, T1 before the second dose of the vaccine and at times T2, T3, T4 and T5 which correspond to 5-7 weeks (Pfizer-BioNTech) or 6-8 weeks (Moderna), 12 weeks, 24 weeks and 52 weeks after the first dose
T cell immunological response	At each time point, the Spike and N-specific T-cell immunity of the 1300 enrolled subjects will be assessed and compared to that observed in a population of healthy subjects at the same time point (see controls).	at 6 times points T0 before vaccine administration, T1 before the second dose of the vaccine and at times T2, T3, T4 and T5 which correspond to 5-7 weeks (Pfizer-BioNTech) or 6-8 weeks (Moderna), 12 weeks, 24 weeks and 52 weeks after the first dose
immunological response in different subgroups	Subgroup analysis on the immunological response will be performed according to the clinical characteristics of the patients, the main diagnosis subgroups according to the eligibility criteria and the treatments they have received. we will compare the immune response with the different clinical characteristics of the patients	1 year
impact of COVID-19 vaccination on patient health status	The impact on health status will be assessed through a questionnaire compiled at T1 and T2 by the physician before the blood sampling. The questionnaire will assess the occurrence of a list of symptoms in the week after the first and second administration of the vaccine.	1 weeks after frist dose and 1 week after second dose
incidence of SARS-CoV-2 infection.	The incidence of SARS-CoV-2 infection will be assessed in terms of number and proportion of patients who during the 52 weeks. SARS-CoV-2 infection will be assessed with: positive to molecular NF swab.	all 52 weeks

Collaborators and Investigators

• Sponsor: Azienda USL Reggio Emilia - IRCCS
• Collaborators: IRCCS San Raffaele; IRCCS Azienda Ospedaliero-Universitaria di Bologna; University of Roma La Sapienza; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; Istituto Clinico Humanitas; IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Regina Elena Cancer Institute; Fondazione IRCCS Policlinico San Matteo di Pavia; Istituto Tumori Giovanni Paolo II, BARI; Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS; Istituti Fisioterapici Ospitalieri
• Investigators: Principal Investigator: Carlo Salvarani, Azienda USL - IRCCS di Reggio Emilia

Publications and helpful links

General Publications

• Di Cosimo S, Lupo-Stanghellini MT, Costantini M, Mantegazza R, Ciceri F, Salvarani C, Zinzani PL, Mantovani A, Ciliberto G, Uccelli A, Baldanti F, Apolone G, Delcuratolo S, Morrone A, Locatelli F, Agrati C, Silvestris N. Safety of third dose of COVID-19 vaccination in frail patients: Results from the prospective Italian VAX4FRAIL study. Front Oncol. 2022 Oct 20;12:1002168. doi: 10.3389/fonc.2022.1002168. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; vaccination; frail patients
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Connective Tissue Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Nervous System Diseases; Hematologic Diseases; Rheumatic Diseases; Collagen Diseases
• Other Study ID Numbers: VAX4FRAIL study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No