Antibody response to a third SARS-CoV-2 vaccine dose in recipients of an allogeneic haematopoietic cell transplantation.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients show impaired antibody (Ab) response to a standard two-dose vaccination against severe acute respiratory syndrome coronavirus-2 and currently a third dose is recommended as part of the primary vaccination regimen. By assessing Ab titres 1 month after a third mRNA vaccine dose in 74 allo-HCT recipients we show sufficient neutralisation activity in 77% of the patients. Discontinuation of immunosuppression before the third vaccine led to serological responses in 50% of low responders to two vaccinations. Identifying factors that might contribute to better vaccine responses in allo-HCT recipients is critical to optimise current vaccination strategies.

Antibody Response to SARS-CoV-2 Vaccination in Patients following Allogeneic Hematopoietic Cell Transplantation.

Vaccines against SARS-CoV-2 have been rapidly approved. Although pivotal studies were conducted in healthy volunteers, little information is available on the safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Here we used a novel assay to analyze patient- and transplantation-related factors and their influence on immune responses to SARS-CoV-2 vaccination over an extended period (up to 6 months) in a large and homogenous group of allo-HCT recipients at a single center in Switzerland. We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivity against SARS-CoV-2 antigens (receptor-binding domain, spike glycoprotein subunits S1 and S2, and nucleocapsid protein) was performed before vaccination, before the second dose, and at 1, 3, and 6 months after the second dose. Patients were stratified to 3 groups: 3 to 6 months post-allo-HCT, 6 to 12 months post-allo-HCT, and >12 months post-allo-HCT. Patients in the 3 to 6 months and 6 to 12 months post-allo-HCT groups developed significantly lower antibody titers after vaccination compared with patients in the >12 months post-allo-HCT group and healthy controls (P < .001). Within the cohort of allo-HCT recipients, patients age >65 years (P = .030), those receiving immunosuppression for prevention or treatment of graft-versus-host disease (GVHD) (P = .033), and patients with relapsed disease (P = .014) displayed low humoral immune responses to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels at 1 month after the second dose of the vaccine but waned substantially in all transplantation groups and healthy controls over time. This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding revaccination and social behavior during the SARS-CoV-2 pandemic.

Rapid Centrifugation in the Routine Hemostasis Laboratory.

BACKGROUND: The use of short and uniform centrifugation schemes contributes significantly to the successful automation of laboratory procedures. It is however unclear if this is applicable to the hemostasis laboratory. OBJECTIVES: This article assesses the accuracy of measurements obtained with a rapid, high-speed centrifugation scheme in a large set of hemostasis tests, covering the full spectrum of values obtained in clinical practice, and using meaningful statistical measures. METHODS: Two citrated plasma samples were obtained from consecutive patients of a tertiary hospital with suspected abnormal hemostasis tests and processed with two centrifugation schemes in parallel: 1,500 × g for 10 minutes and 3,137 × g for 7 minutes. The following tests were conducted: prothrombin time (n = 125), international normalized ratio (n = 146), activated partial thromboplastin time (n = 119), thrombin time (n = 105), fibrinogen (n = 125), factor (F)II (n = 69), FV (n = 64), FVII (n = 64), FX (n = 67), FVIII (n = 55), FIX (n = 37), FXI (n = 35), and FXIII (n = 20), D-dimer (n = 34), antithrombin (n = 31), anti-Xa activity (n = 30), von Willebrand antigen (n = 25), and von Willebrand activity (VWF:GPIbM; n = 27). RESULTS: A wide range of results were obtained in all tests. Spearman's rank correlation coefficient was at least 0.95 for all tests except FV, FIX, and FXI. The coverage probability π at a given deviation index κ of 15% was above 0.9 for all tests except FV, FVII, FX, FVIII, FIX, FXI, and VWF:GPIbM, suggesting a lack of agreement. CONCLUSION: Our results suggest that high-speed centrifugation is applicable to the majority of routine hemostasis parameters. The coverage probability was more sensitive than Spearman's rank correlation to detect disagreement among centrifugation schemes.