Immunocompromised Patients

Respiratory syncytial virus (RSV) is a major cause of acute respiratory infections (ARIs), which occur in seasonal outbreaks. Among the adult population, immunocompromised individuals, particularly lung transplant recipients and recipients of allogeneic haematopoietic stem cell transplants (HSCTs), are at the highest risk of severe ARI. RSV can also cause prolonged inflammation of the airways, leading to persistent deterioration in lung function. Thus, in lung transplant recipients, RSV is a major cause of chronic lung allograft dysfunction (CLAD), the leading cause of lung transplant failure and mortality beyond the first post-transplant year. In recipients of ACSH, RSV infection is associated with the onset and/or worsening of bronchiolitis obliterans syndrome, which leads to increased mortality. Preventing RSV-associated lower respiratory tract disease (LRTD) and its short- and long-term consequences in these populations is therefore a key priority. Three inactivated RSV vaccines, targeting the RSV fusion glycoprotein in its pre-fusion conformation (RSVpreF), have recently been approved for use in adults. These comprise two recombinant protein vaccines - one with an adjuvant (RSVpreF3-AS01, Arexvy®, GSK) and one without (RSVpreF, Abrysvo®, Pfizer) - and one mRNA vaccine. Although these vaccines have demonstrated their safety, immunogenicity and efficacy (reducing the risk of RSV-related IMRI by approximately 80-85 per cent) in adults aged 60 and over, the pivotal trials excluded immunocompromised patients. To date, there is limited data on the efficacy, immunogenicity and tolerability of these vaccines in high-risk immunocompromised populations, such as recipients of bone marrow transplants and allogeneic stem cell transplants. Real-world studies suggest that RSV vaccines may reduce the risk of RSV-associated acute respiratory infection and hospitalisations in elderly immunocompromised adults. With regard to immunogenicity, the available cohort studies, conducted on small sample sizes, indicate that the vaccine response is heterogeneous and, overall, lower than that observed in immunocompetent older people. Preliminary data suggest that booster vaccination regimens may be necessary to optimise the immune response in these populations. Given the significant morbidity associated with RSV in recipients of bone marrow transplants and allogeneic stem cell transplants, it is a priority to assess the immunogenicity and safety profile of RSV vaccines, and to determine the optimal vaccination schedule for these high-risk, immunocompromised populations. The investigators hypothesise that the immune response to RSV vaccines in severely immunocompromised TP and ACSH recipients is weaker than in immunocompetent older adults, and that enhanced vaccination strategies may be required. In this study, two vaccination strategies will be evaluated in these populations: * a single dose of the adjuvanted RSVpreF3-AS01 vaccine (Arexvy®), * or a booster regimen comprising two doses of the non-adjuvanted RSVpreF vaccine (Abrysvo®), administered one month apart.

The MARINA study (bioMARkers of INflammation, infection, and immunity in critical cAre) is a multicenter, prospective and retrospective observational cohort study designed to evaluate the diagnostic and prognostic role of inflammatory and immune biomarkers in critically ill patients. The study enrolls adult patients (≥18 years) admitted to intensive care or step-down units who present with signs or symptoms of active infection, including sepsis and septic shock. Three main patient populations are targeted: (1) patients with suspected or confirmed infection (community- or hospital-acquired); (2) patients undergoing high-risk major surgery (cardiac, thoracic, or abdominal) under general anesthesia; and (3) immunocompromised patients (solid organ transplant, HSCT, bone marrow transplant, CAR-T cell therapy, or other severe immunosuppression). Serial measurements of established and emerging biomarkers - including procalcitonin, C-reactive protein, MR-proadrenomedullina, copeptin, ferritin, interleukin-6, troponin, D-dimer, lactate, lymphocyte subpopulations, and immunoglobulins - are collected at predefined time points (T1: within 24 hours; T2: within 72 hours; T7: at day 7 of ICU admission) and integrated with clinical data on a dedicated electronic platform. The primary endpoint is 28-day mortality. Secondary endpoints include assessment of organ damage, clinical severity, response to treatment, infectious complications (including VAP and bacteremia), superinfections (bacterial, viral, fungal), ICU and hospital length of stay, and the ability of biomarkers to guide antimicrobial de-escalation. Long-term survival at 90 and 180 days is also assessed. A minimum sample size of 200 patients (prospective phase) is planned across participating centers in Italy and Spain. The study duration is four years from ethical approval.

Evaluate new diagnostic methods using qPCR on non-invasive samples, compared with reference techniques for the positive diagnosis of pneumocystis (PcP) in immunocompromised patients

Herpes zoster (HZ) is a serious health problem whose incidence and severity increase with the decline of cell-mediated immunity (CMI) because of age and immunocompromised (IC) status. Subclinical reactivation are described and may boost the adaptive specific immunity. T cells play a major role in preventing reactivation of Varicella Zoster virus (VZV), with a contribution of both CD4 and CD8 T cells. Accordingly, the suppression of VZV-specific T cells preceded the occurrence of HZ. Moreover, several observations support a role of B cells in contributing to the overall protection against HZ as patients with primary antibody deficiency, common variable immunodeficiency, or patients treated with B-cell depleting therapies or Janus Kinase inhibitors (JAKis) show a higher risk of HZ. The functional effectiveness of CMI can be significantly affected by different diseases (e.g. cancer and immune-mediated inflammatory diseases, IMIDs) and/or by ongoing immune-targeted therapy, giving these patients at high risk for VZV reactivation. The new recombinant zoster vaccine (RZV) reduces the risk of HZ, and vaccination is encouraged in IC individuals, including those with cancer and IMIDs. Despite the efficacy and safety of RZV in healthy adults, data on IC patients are scarce. In particular, the immunogenicity of the new vaccine in frail subjects is not fully understood. On the one hand, immunosuppressive treatments can compromise the residual immunity to VZV but also the response to RZ . Several therapies are known to affect B cell response such as Rituximab or CAR T cells; other treatments reduce the T cell functionality, such as T-cell inhibitors (Cytotoxic T-lymphocyte Antigen 4-Immunoglobulin, CTLA4-Ig; abatacept), the JAK is, as well as by chemotherapy. To date, the vaccination is not approved in paediatric patients. However, the investigation of the VZV-specific immunological profile in frail paediatric patients could represent a valuable tool for understanding the potential vaccination strategies in these categories. The study and definition of an immune profile associated with a high risk of viral in RZV vaccinated patients with IC can be useful for identifying patients' candidates for preventive antiviral treatments. This is an observational multicentric prospective cohort study. The general objective is to assess the immunogenicity of RZV vaccination in terms of the induction of humoral and cell-mediated immune responses in selected frail (altered immunocompetence) populations, including rheumatologic, oncologic, neurologic and hematologic patients. Primary Objective: To define the overall rate of humoral responders patients after the second dose of RZV administration. Primary Endpoint: The rate of "humoral responders" will be defined as the percentage of patients showing ≥ 4 times of gE-specific IgG response (IU/mL) after the second dose (T1m) respect to baseline (T0) Secondary Objective 2.1: To define the overall increase of humoral response after the second dose of RZV administration. Secondary Objective 2.2: To characterize the immunogenicity induced by RZV vaccine in the different study cohorts (rheumatologic, oncologic, neurologic and hematologic patients) Secondary Objective 2.3: To evaluate the kinetics of humoral response during the first year after the vaccination Secondary Objective 2.4: To characterize gE-specific T cell mediated response elicited by RZV vaccination in overall patients Secondary Objective 2.5: Evaluation of the incidence of adverse reactions (AR) to the RZV vaccine, local and systemic, solicited and unsolicited, within the period of four weeks after the second dose of RZV. Secondary Objective 2.6: Evaluation of the incidence of reactivation of VZV cases after the second dose of RZV.

Transplants have improved clinical conditions for many patients with haematological diseases and end-stage organ diseases. However, immunosuppressive therapies that are necessary for avoiding organ rejection have a crucial impact in the occurrence of opportunistic infections. Despite the development of effective antimicrobial agents, infectious diseases are still related to mortality and morbidity in immunocompromised patients. Immune function assays can be adopted for monitoring T-cell function and eventually modify immunosuppression. Given the inverse relationship between cellular immune reconstitution and risk of infection, many transplant centers prospectively monitor immune recovery post-transplant. Some basic methods are useful, including white blood cells and T-lymphocyte subsets count. Given the complexity of immune responses required to resolve infections, functional assays are necessary and the only available FDA-approved one is Cyclex-Immuknow. Viral infections are common in patients with T-cell deficiencies and are of particular concern in those receiving high dose steroids. Opportunistic infections are common during the period of highest immunosuppression while community acquired infections, including fungal and respiratory viruses infections, have to be considered in the long-term period. Reduced CD4+ and CD8+ T-lymphocyte counts correlate with risk of opportunistic infection, including human cytomegalovirus (HCMV). Moreover, a decrease in human Rhinovirus (HRV) load in pediatric hematopoietic stem cell transplant recipients (HSCTRs) was associated with a significant increase in T-CD4+, T-CD8+ and NK lymphocytes, suggesting that cellular immunity have a crucial role in viral clearance and infectious control. A recent study showed that poor NK-cell cytotoxic activity is associated with increased risk for severe infections in kidney-graft recipients, suggesting that assessment of NK-cell function may be used as a predictor of infection in immunocompromised patients. Moreover, it has been recently reported that NKG2C genotype influences receptor function and NKG2C+ NK cell number in HCMV seropositive subjects. In detail, NKG2C genotype is significantly associated with HCMV viremia frequency and related disease after lung transplant and with symptomatic CMV infection after kidney transplant. Beside the use of non-specific immunological markers, the lack of standardized quantitative measures of protective immune functions specific for different opportunistic pathogens represents a challenge for clinicians. Overall, a comprehensive approach based on the use of combined non-specific and pathogen-specific immune assays may help in the definition of a composite immune risk profile of immunocompromised patients. The ultimate goal of this research is the definition of algorithms of infectious risk in immunocompromised patients, leading to a more adherent administration of immunosuppressive and antimicrobial therapies as well as to a personalized strategy of patients' management. Moreover, the design of new immunological assays that can be standardized and used in the clinical practice will be obtained. Currently, even if an immunological monitoring of immunocompromised patients is recommended, no standardized assays and protocols are available, especially for the use of antigen-specific or functional assays. The introduction of diagnostics algorithms will be useful for the stratification of patients at high risk of infections that will be monitored more frequently in order to prevent severe infections. Similarly, the administration of immunosuppressive drugs or ad hoc therapies might be tailored according to the risk of infections or complications. Objective is to identify a composite immune score measured either before or one month after transplant/chemotherapy able to define the risk for clinically significant infections (e.g. infections requiring antimicrobial therapy or hospitalization) during the following three months. Primary endpoint: To identify a composite immune score measured either before or one month after transplant/chemotherapy able to define the risk for clinically significant infections (e.g. infections requiring antimicrobial therapy or hospitalization) during the following three months. Secondary endpoints: * To evaluate the prognostic effect of the immunological score measured before or at first month after transplant/chemotherapy on the risk of severe infection during the following 6-12 months * To compare the role of the composite immunological score with specific assays against each pathogen. * To develop simple and rapid assays using whole blood to evaluate specific pathogen responses

The goal of this observational study is to characterize nasal mucosal immunity to respiratory viruses, such as SARS-CoV-2, in immunocompromised individuals and healthy volunteers. The study involves adults of any sex, between 18 and 90 years old, including both immunocompromised patients with medical conditions or treatments that can affect immune cell functions and healthy controls with no underlying medical conditions declared, no clinical history of immunodeficiency or use of immunosuppressive medications. Researchers will compare immunocompromised participants to healthy volunteers to determine how underlying immunodeficiency and related treatments affect immune cell composition and virus-specific responses.