COVID19 Vaccine in SOT Adult Recipients

Study Overview
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Brief Summary
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Background: ISHLT and AASLD guidelines recommend SARS-CoV2 vaccination in all individuals undergoing lung and liver transplantation, but there are currently scarce data on the safety and efficacy of these vaccines in this population. In Italy, immunocompromised patients have received the indication to be administered mRNA vaccines only. Primary outcome: safety and reactogenicity Secondary outcomes: immunogenicity and prevention of COVID19 Visits and timepoints: T0: before first dose administration: visit and venous sampling to assess baseline COVID19 serum status Telephone calls to assess safety and reactogenicity 1 and 2 days after each dose of vaccination T21 or 28 (based on vaccine; mRNA BNT162b2 and mRNA-1273, respectively): visit, venous sampling to assess immunogenicity Follow up visits after 60, 120, 180 and 365 from T0: visit and venous sampling to assess immunogenicity

Detailed Description
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Several studies indicate that solid organ transplant recipients are at increased risk of severe SARS-CoV2 disease (COVID19) and increased mortality from it (Pereira MR, AmJT 2020; Fernandez-Ruiz M, AmJT 2020; Kates OS, ClinInfectDis 2020). Both ISHLT (International Society of Heart and Lung Transplantation) and AASLD (American Association for the Study of Liver Disease) guidelines recommend vaccination of all individuals undergoing lung and liver transplantation, starting from 3/6 months after transplantation. In Italy, the Ministry of Health and the Italian Medicines Agency (AIFA) have established that immunosuppressed subjects following organ transplantation are worthy of vaccination with mRNA vaccines, since the latter are currently those with the greatest efficacy demonstrated among those approved in this country. Within the Institution where this study will be conducted, patients undergoing lung and liver transplantation will be vaccinated, according to priority levels dictated by existing co-morbidities and by the time elapsed since transplantation, with the COMIRNATY mRNA vaccine (BNT162b2) administered according to the vaccination schedule of 2 doses at a distance of 21 days from each other or with the MODERNA vaccine (mRNA-1273) administered according to a vaccination schedule of 2 doses at a distance of 28 days from each other. At present, no definitive data are available on the efficacy and the immunogenicity of anti-SARS-CoV-2 vaccines in solid organ transplant recipients, although the initial findings are reassuring. mRNA vaccines appear to be safe in the transplant population, and have not raised any concern at present about the possible onset of rejection or other serious adverse events in the first period after their administration (Boyarsky BJ, Transplantation 2021). The primary objective of this study is to evaluate the safety and reactogenicity of antiSARS-CoV2 mRNA vaccines in SOT recipients. Secondary outcomes include immunogenicity and efficacy (see Outcome paragraph for details). Visits and timepoints: T0: before first dose administration: visit and venous sampling to assess baseline COVID19 serum status Telephone calls to assess safety and reactogenicity 1 and 2 days after each dose of vaccination T21 or 28 (based on vaccine; mRNA BNT162b2 and mRNA-1273, respectively): visit, venous sampling to assess immunogenicity Follow up visits after 60, 120, 180 and 365 from T0: visit and venous sampling to assess immunogenicity

Official Title
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Safety and Immunogenicity of the SARS-CoV2 Vaccine in Solid Organ Transplantation (Lung and / or Liver) Adult Recipients

Conditions
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COVID-19, Vaccine Adverse Reaction, Vaccine Response Impaired, Vaccine Reaction, Lung Transplant; Complications, Liver Transplant; Complications, Vaccination

Intervention / Treatment
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* Biological: COVID19 mRNA vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Patient's written informed consent Exclusion Criteria: Lung transplant being performed in the previous 6 months Liver transplant being performed in the previous 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LuTx recipients<br>Lung Transplant recipients | Biological: COVID19 mRNA vaccine<br>* Administration of COVID19 mRNA vaccine<br>|
| OLT recipients<br>Orthotopic Liver Transplant recipients | Biological: COVID19 mRNA vaccine<br>* Administration of COVID19 mRNA vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and reactogenicity | Primary endpoints: Incidence of systemic and local adverse events (and their degree) in the subsequent 7 days after each vaccine administration in this population Incidence of unusual adverse events (and their degree) in the subsequent 28 days after each vaccine administration in this population Incidence of serious adverse events (SAEs) and sentinel events (NOCMCs, new onset chronic medical conditions, and MAAEs, medically-attended adverse events) over a 1-year follow-up period after administration of the first vaccine dose in this population | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity - antibody response, using ImmunoAssay in ECLIA for the quantitative detection of anti-protein S1 (spike) antibodies (including IgG) | Geometric mean titer (GMT) of SARS-CoV2 anti-protein S1 total Ig (spike) antibody titers (GMT) at each timepoint Percentage of individuals experiencing seroconversion at each timepoint Increase of antibody titers (GMFR, geometric mean fold rise) from T0 | 365 days | 
| Immunogenicity - Tcell response, using IGRA interferon-γ ELISpot, performed 60 days after the administration of the first vaccine dose | - Evaluation of the IFN-γ ELISpot-mediated T-cell response for different stimuli (peptides of proteins S1, S2, N, M, E and mix of structural proteins), measured with the following unit of measurement, i.e. IFN -γ spots / 250,000 PBMC (peripheral blood mononuclear cell) for each stimulus, 60 days after the first vaccine dose | 60 days | 
| Prevention of COVID19 | - Incidence of SARS-CoV2 infection, diagnosed with positivity of nasopharyngeal swab (SARS-CoV2 RNA search with RT-Real time PCR method) | 365 days | 
| Prevention of severe COVID19 | To evaluate the actual prevention of severe forms of SARS-CoV2 infection in this population - Incidence of severe forms of SARS-CoV2 infections, defined as requiring hospitalization of the patient and / or conditioning pneumonia / respiratory failure / sepsis / septic shock / ARDS | 365 days | 
| Immunogenicity and immunosuppression level | To compare the obtained (both antibody and T cell mediated) immunogenicity with the immunosuppression levels | 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID19, Vaccination, Vaccine, Transplant, Solid organ transplant, Lung transplant, Liver transplant