Assessment of COVID-19 Incidence and Severity Among Recipients of Allogenic Stem Cell Transplant After 1 or 2 mRNA Booster Doses During the Omicron Wave in France.

This cohort study assesses the incidence and severity of COVID-19 among vaccinated recipients of allogenic stem cell transplant in a single center after 1 or 2 messenger RNA booster doses during the Omicron wave in France.

Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients.

A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.

Effectiveness of a third dose of BNT162b2 anti-SARS-CoV-2 mRNA vaccine over a 6-month follow-up period in allogenic hematopoietic stem cells recipients.

This study reports the effectiveness of three injections of BNT162b2 anti-SARS-CoV-2 mRNA vaccine in 141 Allo-HSCT recipients with a median follow-up of 6 months post-third shot. We demonstrate a long-term high protection of Allo-HSCT recipients since only 2 infections and one death related to COVID-19 occurred.

B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4+and CD8+ T cells, B cells, and natural killer cells at the time of V1. Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titer. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T cell and B cell counts, ongoing I/C treatment, and a haploidentical donor were characteristic of nonhumoral responders. However, multiparameter analysis showed that B cell aplasia was the sole factor predicting the absence of a specific immune response (odds ratio, 0.01; 95% confidence interval, 0.00 to 0.10; P < 10-3). Indeed, the rate of humoral response was 9.1% in patients with B cell aplasia versus 95.9% in patients with a B cell count >0 (P < 10-9). These results advocate for the administration of anti-SARS-CoV-2 vaccination in allo-HSCT recipients as early as peripheral B cell levels can be detected, and also suggest the need for close monitoring of B-cell reconstitution after Allo-HSCT.

SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine.

BACKGROUND: At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. METHODS: SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4+ and CD8+ T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. RESULTS: A strong TNF-α+ response from SARS-CoV-2-specific CD4+ T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). CONCLUSIONS: T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo-HSCT recipients.

Anti-SARS-CoV-2 vaccines in recipient and/or donor before allotransplant.

The impact of pre-transplant anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in 20 recipients of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and/or their donors is reported here, showing that the persistence of anti-SARS-CoV-2 antibodies can be detected in almost all patients, whatever the type of vaccine used, and up to 9 months post transplant. Also, an anti-SARS-CoV-2 spike glycoprotein CD3+ T-cell response could be detected in six (35%) of 17 evaluable patients. This study provides a rationale to consider anti-SARS-CoV-2 vaccination of both recipients and donors before Allo-HSCT.

[How to deal with an unexpected event that could alter the normal activity of cellular therapy? Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Comment faire face à un événement inattendu pouvant modifier l'activité normale de thérapie cellulaire ? Recommandations de la Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

The SARS-CoV-2 (COVID-19) pandemic has rapidly impacted cell therapy activities across the globe. Not only was this, unexpected event, a threat to patients who had previously received hematopoietic cell transplantation or other cell therapy such as CAR-T cells, but also, it was responsible for a disruption of cell therapy activities due to the danger of the virus and to the lack of solid scientific data on the management of patients and donors. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) devoted a workshop to issue useful recommendations in such an unexpected event in order to harmonize the actions of all the actors involved in cellular therapy programs so that we can collectively face, in the future, the challenges that could threaten our patients. This work is not specifically dedicated to the SARS-CoV-2 outbreak, but the latter has been used as a concrete example of an unexpected event to build up our recommendations.

Safety and immunogenicity of a first dose of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem-cells recipients.

This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer-BioNTech) in 112 Allo-HSCT patients. Antibody response to SARS-CoV-2 spike protein receptor-binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non-randomized control arm of 26 healthy controls. This study shows that a first dose of SARS-CoV-2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p < 0.001). Factors influencing the absence of response in patients were recent transplantation (<2 years), lymphopenia (<1 × 109/L) and immunosuppressive treatment or chemotherapy at the time of vaccination.

A longitudinal study of SARS-CoV-2 infected patients shows high correlation between neutralizing antibodies and COVID-19 severity (preprint)

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection from re-infection and, thus, for public health policy and for vaccine development against the COVID-19. Here, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum specimens from a cohort of 140 SARS-CoV-2 qPCR-confirmed patients, including patient with mild symptoms but also more severe form including those that require intensive care. We show that nAb titers were strongly correlated with disease severity and with anti-Spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers, whereas patients with milder disease symptoms displayed heterogenous nAb titers and asymptomatic or exclusive outpatient care patients had no or poor nAb levels. We found that the nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery, as compared to individuals infected with alternative coronaviruses. We show the absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAb against SARS-CoV-2 infection. Finally, we found that the D614G mutation in the Spike protein, which has recently been identified as the major variant now found in Europe, does not allow neutralization escape. Altogether, our results contribute to the understanding of the immune correlate of SARS-CoV-2 induced disease and claim for a rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2.