Three doses of a recombinant conjugated SARS-CoV-2 vaccine early after allogeneic hematopoietic stem cell transplantation: predicting indicators of a high serologic response-a prospective, single-arm study.

Background: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-binding domain (RBD)-tetanus toxoid (TT)-conjugated platform shortly after allo-HSCT in the developing country of Iran. Methods: This prospective, single-arm study aimed to investigate immunogenicity and its predictors following a three-dose SARS-CoV-2 RBD-TT-conjugated vaccine regimen administered at 4-week (± 1-week) intervals in patients within 3-12 months post allo-HSCT. An immune status ratio (ISR) was measured at baseline and 4 weeks (± 1 week) after each vaccine dose using a semiquantitative immunoassay. Using the median ISR as a cut-off point for immune response intensity, we performed a logistic regression analysis to determine the predictive impact of several baseline factors on the intensity of the serologic response following the third vaccination dose. Results: Thirty-six allo-HSCT recipients, with a mean age of 42.42 years and a median time of 133 days between hematopoietic stem cell transplant (allo-HSCT) and the start of vaccination, were analyzed. Our findings, using the generalized estimating equation (GEE) model, indicated that, compared with the baseline ISR of 1.55 [95% confidence interval (CI) 0.94 to 2.17], the ISR increased significantly during the three-dose SARS-CoV-2 vaccination regimen. The ISR reached 2.32 (95% CI 1.84 to 2.79; p = 0.010) after the second dose and 3.87 (95% CI 3.25 to 4.48; p = 0.001) after the third dose of vaccine, reflecting 69.44% and 91.66% seropositivity, respectively. In a multivariate logistic regression analysis, the female sex of the donor [odds ratio (OR) 8.67; p = 0.028] and a higher level donor ISR at allo-HSCT (OR 3.56; p = 0.050) were the two positive predictors of strong immune response following the third vaccine dose. No serious adverse events (i.e., grades 3 and 4) were observed following the vaccination regimen. Conclusions: We concluded that early vaccination of allo-HSCT recipients with a three-dose RBD-TT-conjugated SARS-CoV-2 vaccine is safe and could improve the early post-allo-HSCT immune response. We further believe that the pre-allo-HSCT SARS-CoV-2 immunization of donors may enhance post-allo-HSCT seroconversion in allo-HSCT recipients who receive the entire course of the SARS-CoV-2 vaccine during the first year after allo-HSCT.

Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .

Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment

High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. Trial registration: Iranian Registry of Clinical Trials (IRCT);IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .