Effectiveness of COVID-19 Vaccine in Hematopoietic Stem Cell Transplant Patients

Study Overview
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Brief Summary
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COVID-19 vaccinations are predicted to be a huge success in pandemic control. However, the majority of the studies were conducted on healthy individuals, and the efficiency of COVID-19 vaccination in post-transplant patients is uncertain. In the setting of HSCT, the extreme immunosuppression caused by the conditioning regimen and the graft versus host disease (GvHD) preventive regimen clearly has an impact on the efficacy and immunogenicity of the COVID-19 vaccine. Given the importance of eliciting early SARS-Cov-2 protective immunity in patients who are undergoing Allo-HSCT and the EBMT recommendation to endorse vaccination as early as 3 months after allo-HCT [7], we conduct this prospective study to investigate the safety and immunogenicity of three doses Pastucovac (an RBD-based SARS-Cov-2 vaccine) at the early post-transplant period in adult Iranian patients who are undergoing Allo-HSCT. We also want to see whether there are any possible predictors, such as the effect of clinical characteristics and lymphocyte subpopulations at the time of vaccination on the serologic response following immunization. The findings of this study will serve to guide future COVID-19 vaccination recommendations in this population, such as the optimal starting time, interval time, and so on.

Detailed Description
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From the start of the study until the sample size of 100 patients is attained, all consecutive adult patients who are candidates for Allo-SCT at HORCSCT, sign a research project consent to administer SARS-CoV-2 vaccination with Pastucovac, and sign a permission to take pre-and post-vaccination blood samples for deposit to the research database, are enrolled in the study. At baseline (before conditioning) and day +30 post-transplant, peripheral blood samples are taken to test particular lymphocyte subpopulations and SARS-CoV-2 IgG titers. All enrolled post-Allo-SCT participants who meet the inclusion criteria including; age ≥ 18 years, successfully engraftment with full donor chimerism, absence of grade 3,4 acute GvHD or severe extensive chronic GvHD, no receive more than 0.5 mg/kg prednisolone, and no positive RT-PCR test for COVID-19 following HSCT are recruited to study from 3 to 12 months after Allo-HSCT and vaccinated with 2 doses of Pastucovac, with a 4-week (±7 days) interval and a booster dose with an 8-week (±7 days) interval from the second dose. Peripheral blood samples are collected before the first dose of vaccine to assess certain immune reconstitution and SARS-CoV-2 IgG titer. The serologic response against the SARS-CoV-2 spike protein (anti-S) is assessed in serum four weeks (± one week) after the first vaccine dose (before the second vaccine), four weeks (± one week) after the second dose, and four weeks (± one week) after the booster dose (third dose).

Official Title
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Evaluation of COVID-19 Vaccine Effectiveness and Immunogenicity in Patients Receiving Hematopoietic Stem Cell Transplantation

Conditions
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COVID-19 Vaccines, Hematopoietic Stem Cell Transplantation (HSCT), Immune System Tolerance

Intervention / Treatment
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* Biological: Pasocovac vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years, successfully engraftment with full donor chimerism, absence of grade 3,4 acute GvHD or severe extensive chronic GvHD, no receive more than 0.5 mg/kg prednisolone, and no positive RT-PCR test for COVID-19 following HSCT Exclusion Criteria: Patients who are not candidates for the COVID-19 vaccine after transplantation due to severe complications. Patients who do not consent to vaccination after transplantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vaccine<br>Patients who are a candidate for HSCT within the the Hematology, Oncology, and Stem Cell Transplantation Research Center of Shariaty Hospital, and agree to be vaccinated with an approved vaccine against the COVID-19 virus. | Biological: Pasocovac vaccine<br>* All enrolled post-Allo-SCT participants who meet the inclusion criteria are recruited to study from 3 to 12 months after Allo-HSCT and vaccinated with 2 doses of Pastucovac, with a 4-week (±7 days) interval and a booster dose at an 8-week (±7 days) interval from the second dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of COVID-19 vaccine effectiveness | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer | 4 weeks (±7 days) post second COVID-19 vaccine | 
| Grade III-IV vaccine-related adverse reactions | Prevalence of reactogenicity, Serious Adverse Events (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR) | 14 days after administration of each vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Acute Graft versus host disease (GvHD) | Measuring how the acute GvHD affect the response to the vaccine | 4-week (±7 days) after second and third (booster) dose of vaccine. | 
| GvHD prophylactic strategy affect immunological response | Measuring how early prophylactic immuno-suppression tapering affect the response to the vaccine | 4-week (±7 days) after third (booster) dose of vaccine. | 
| Immune cells recovery predicting the response to the COVID-19 vaccine | Measuring how early post HSCT Immune subsets reconstitution including T cells, NK cells, and B cells predict the seroconversion after second dose of vaccine. | 4-week (±7 days) after third (booster) dose of vaccine. | 
| seroconversion after second dose of vaccine | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer in patients starting their vaccination course 3-6 months after HSCT | 4-week (±7 days) after second dose of vaccine. | 
| seroconversion after second dose of vaccine | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer in patients starting their vaccination course 6-12 months after HSCT. | 4-week (±7 days) after second dose of vaccine. | 
| seroconversion after first dose of vaccine | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer | 4-week (±7 days) after first dose of vaccine. | 
| seroconversion after third (booster) dose of vaccine | defined as a rising ≥ 4-fold in SARS-CoV-2 binding antibody titer compared to the pre-vaccine titer | 4-week (±7 days) after third (booster) dose of vaccine. | 
| Incidence and severity of COVID-19 infections | Determine incidence and severity of COVID-19 infections by 6 months following immunization with a SARS-CoV-2 vaccine. | 6 months following start of immunization | 
| Correlation of seroconversion with patient characteristics | Determine how the patients characteristics including age, sex, performance score, and underlying disease affect on seroconversion | 4-week (±7 days) after second and third (booster) dose of vaccine. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation, SARS-CoV-2 specific IgG , immune reconstitution, COVID-19 vaccine efficacy