Further studies in a larger cohort of patients are warranted to clarify the role of the different lymphocytes subpopulations in the generation of a long-lasting anti SARS-COV-2 immunization in HSCT recipients

Further studies in a larger cohort of patients are warranted to clarify the role of the different lymphocytes subpopulations in the generation of a long-lasting anti SARS-COV-2 immunization in HSCT recipients. Data Availability Statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics Statement The studies involving human participants were reviewed and approved by CERM. 45 healthy subjects. Of the 50 patients tested, 12 did not develop any antibody response, including 6 patients undergoing autologous (16%) and 6 allogeneic HSCT (50%). Cyclosporine administration in allogeneic recipients and prior administration of Rituximab in the autologous setting correlated with lower antibody titers (p 0.0003 and p=0.000, respectively). Flow cytometry of peripheral blood samples, performed 30 days after the vaccination, showed a significant correlation between the antibody response to Sars-COV2 and an increased number in CD19+ B lymphocytes (p = 0.0003) and CD56+ natural killer (NK) cells (p = 0.00). In conclusion, prior Rituximab before autologous HSCT and cyclosporine administration after allogeneic HSCT negatively affected the antibody response to Sars-COV2 vaccine, possibly due to their immunosuppressive action on CD20 +B cells and T cells, respectively. The correlation between seroconversion to Sars-COV2 and higher number of CD19 + B cells and CD56+ NK cells, suggests a central role for B and NK cells in the Mcl1-IN-4 development of COVID-19 immunity after vaccination with a mRNA-based platform. strong class=”kwd-title” Keywords: SARS-COV2, immune response, vaccine, allogeneic, autologous, transplant Introduction Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome computer virus (SARS-CoV-2) has decided a global health care crisis. Most of the end-organ complications that characterize severe COVID-19 are linked to a deregulated immune response that follows SARS-CoV-2 infection. Phase 3 trials of COVID-19 mRNA-based vaccines showed an efficacy greater than 90% in preventing symptomatic infection, following two doses administered 3 to 4 4 weeks apart. Furthermore, the risk of severe illness from COVID-19 has been reported to be lowered by more than 90% after vaccination (1, 2). Cspg2 The cumulative observational evidence suggests that hosts with altered immunity including, in particular, hematopoietic stem cell transplantation (HSCT) recipients, may be at elevated risk of complications and death due to SARS-CoV-2 contamination (3). This patient population, accordingly, needs special attention, as infections represent a main concern after HSCT and are a major cause of transplant related mortality. Up to now, data are lacking on the immune response to SARS-CoV-2 contamination in patients receiving chronic immunosuppressive therapies. In addition, it is still unclear if mRNA-based COVID-19 vaccines are effective in patients submitted to HSCT, and there are several other unanswered questions about COVID-19 vaccinations in patients on immunosuppressive brokers (4). We thus planned to study the immune response after the administration of mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech) in HSCT recipients. Materials and Methods On March 2021, as suggested by GITMO and SIE indications (5), 50 HSCT recipients (38 autologous HSCT and 12 allogeneic HSCT, all transplanted in our Unit) (Table 1) were vaccinated with the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech), according to the Mcl1-IN-4 standard protocol (two doses of 30 g administered three weeks apart) (6). None of these patients had previously reported SARS-CoV-2-infections; 50% of allo-HSCT patients were receiving immunosuppressive medication(s) at the time of vaccination. Table 1 Patients characteristics and antibody response to Mcl1-IN-4 Sars-COV2 vaccination. thead th valign=”top” align=”left” rowspan=”1″ colspan=”1″ /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ N (%) /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Production of Anti Sars-COV2 IgG antibody (% of patients) /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ p-value /th /thead All patients50 (100)76% Sex ?Male28 (56)78%ns?Female22 (44)76% Age (years) ?6027 (54)66%0.0003? 6023 (46)87% HSCT Mcl1-IN-4 ?Autologous38 (76)87%0.0000?Allogeneic12 (24)50% Diagnosis (auto-HSCT) ?Multiple myeloma22/38 (58%)95%NA?Non-Hodgkin lymphoma14/38 (37%)71%?Hodgkin lymphoma2/38 (5%)100% Diagnosis (allo-HSCT) ?Acute myeloid leukemia7/12 (59%)57%NA?Acute lymphoblastic leukemia4/12 (33%)25%?Myelodysplastic Syndrome1/12 (8%)100% Prior Rituximab administration (NHL only) ?Yes11/14 (78)54%0.0000?No3/14 (22)100% Time from last Rituximab administration ?Less than 1 12 months5 (45)20%0.00?More than 1 12 months6 (55)83% Patients receiving immunosuppressive therapy (allo-HSCT) ?Yes6 (50)17%0.0003?No6 (50)83% GVHD (allo-HSCT) ?Yes5 (42)60%0.16?No7 (58)43% Lymphocyte subpopulation (flow cytometry) B CD19+/mmc (40 patients)?10017 (42)65%0.0003? 10023 (58)91%T CD4+/mmc (43 patients)?20017 (39)70%0.07? 20026 (61)77%T CD8+/mmc (43 patients)?30012 (28)83%0.001? 30031 (72)71%NK CD56+/mmc (41 patients)?10010 (24)40%0.0000? 10031 (76)87% Open in a separate windows HSCT, hematopoietic stem cell transplantation; NHL, non-Hodgkin lymphoma; ns, not significant; NA, not applicable. Serum samples of all patients were tested for SARS-CoV-2 IgG against the Spike Mcl1-IN-4 glycoprotein, using an approved anti-SARS-CoV-2 IgG CLIA (LIAISON? SARS-CoV-2 TrimericS IgG assay, Diasorin, Saluggia, Italy), 30 days after the second dose of vaccine. According to the manufacturers recommendations for the CLIA, an Arbitrary Models per milliliter (AU/mL) ratio of 12.0 was considered to be negative and 15.0 to be positive (borderline 12-15). In addition, the antibody response was compared to a control group of 45 healthy subjects, vaccinated at the same time and with the same modalities. Statistical analysis was performed using Chi-square Test to determine the correlation between antibody response and the following variables: age, sex, type of transplant, precedent Rituximab (RTX) therapy, immunosuppressive therapy, lymphocyte subpopulations.