Risk factors and characteristics influencing humoral response to COVID-19 vaccination in patients after allogeneic stem cell transplantation

Abstract

IntroductionVaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is approved and recommended for immunocompromised patients such as patients after allogeneic stem cell transplantation (allo-SCT). Since infections represent a relevant cause of transplant related mortality we analyzed the advent of immunization to SARS-CoV-2 vaccination in a bicentric population of allogeneic transplanted patients.MethodsWe retrospectively analyzed data of allo-SCT recipients in two German transplantation centers for safety and serologic response after two and three SARS-CoV-2 vaccinations. Patients received mRNA vaccines or vector-based vaccines. All patients were monitored for antibodies against SARS-CoV2-spike protein (anti-S-IgG) with an IgG ELISA assay or an EIA Assay after two and three doses of vaccination.ResultsA total of 243 allo-SCT patients underwent SARS-CoV-2 vaccination. The median age was 59 years (range 22-81). While 85% of patients received two doses of mRNA vaccines, 10% had vector-based vaccines and 5% received a mixed vaccination. The two vaccine doses were well tolerated with only 3% patients developing a reactivation of graft versus host disease (GvHD). Overall, 72% of patients showed a humoral response after two vaccinations. In the multivariate analysis age at time of allo-SCT (p=0.0065), ongoing immunosuppressive therapy (p= 0.029) and lack of immune reconstitution (CD4-T-cell counts <200/μl, p< 0.001) were associated with no response. Sex, intensity of conditioning and the use of ATG showed no influence on seroconversion. Finally, 44 out of 69 patients that did not respond after the second dose received a booster and 57% (25/44) showed a seroconversion.DiscussionWe showed in our bicentric allo-SCT patient cohort, that a humoral response could be achieve after the regular approved schedule, especially for those patients who underwent immune reconstitution and were free from immunosuppressive drugs. In over 50% of the initial non-responders after 2-dose vaccination, a seroconversion can be achieved by boostering with a third dose.

Vaccine schedule recommendations and updates for patients with hematologic malignancy post‐hematopoietic cell transplant or CAR T‐cell therapy

“…[89][90][91][92][93][94] Non-mRNA COVID-19 vaccines are also available, including nonreplicating competent adenovirus vector vaccines (AstraZeneca/ ChAdOx1-S and Johnson&Johnson/Jansen/Ad26.COV2-S), as well as the recombinant nanoparticle protein-based vaccine Novavax/NVX-CoV2373, although published safety and efficacy data are limited in HCT recipients. 75,[95][96][97] In a small study of hemato-oncological patients, Ad26.COV2-S appeared safe as a heterologous vaccine booster after two doses of BNT162b2 vaccine. 98 In hematology malignancy patients with diseases and treatments impacting B-cell immunity, in those who received two doses of ChAdOx1 vaccination followed by an mRNA vaccine, even in the absence of seroconversion robust SARS-CoV-2-specific T-cell immunity was documented.…”

“…Non‐mRNA COVID‐19 vaccines are also available, including non‐replicating competent adenovirus vector vaccines (AstraZeneca/ChAdOx1‐S and Johnson&Johnson/Jansen/Ad26.COV2‐S), as well as the recombinant nanoparticle protein‐based vaccine Novavax/NVX‐CoV2373, although published safety and efficacy data are limited in HCT recipients 75,95–97 . In a small study of hemato‐oncological patients, Ad26.COV2‐S appeared safe as a heterologous vaccine booster after two doses of BNT162b2 vaccine 98 .…”

Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: Respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients

“…People with hematological malignancies (HM) continue to represent a group of patients with a significantly higher risk of developing severe COVID‐19 compared with immunocompetent patients in terms of morbidity, hospitalization, and mortality, regardless of their vaccination status [ 6 ]. Response to vaccination is lower than in the general population with a positive serology in about 80% of HM patients after three or four doses of the SARS‐CoV2 vaccine [ 7 , 8 ]. Specific therapies, such as anti‐CD20 antibodies, BTK inhibitors, and stem cell transplantation, are known to be associated with lower rates of seroconversion [ 9 , 10 , 11 ].…”

Comparable CD8+ T‐cell responses to SARS‐CoV‐2 vaccination in single‐cell transcriptomics of recently allogeneic transplanted patients and healthy individuals

“…Email: benedikt.obermayer@bihcharite.de [1][2][3] However, numerous studies have shown that hematologic patients in general, and allogeneic hematopoietic stem cell transplantation (ASCT) patients in particular, have a significantly weaker vaccine response than healthy controls, with a substantial number of patients failing to develop a protective immunity at all. [4][5][6][7][8][9][10][11][12][13][14] The current knowledge of vaccine response in patients after ASCT is limited to data on measurements of serological responses and in vitro measurements of specific T-cell immunity at various, commonly late time points after transplantation.…”