scholarly journals Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy

2021 ◽  
Author(s):  
Matthias B. Moor ◽  
Franziska Suter-Riniker ◽  
Michael P. Horn ◽  
Daniel Aeberli ◽  
Jennifer Amsler ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Vaccine Dose ◽  
Lymphocyte Subpopulation ◽  
University Hospital ◽  
Healthy Controls ◽  
Vaccine Response ◽  
Treatment History ◽  
History Of ◽  
Anti Cd20

Background B-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation. Methods Patients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by IFN-g release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29). Results Anti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-g; release was detected in 17% of patients and 86% of healthy controls (p<0.001). Only 5% of patients, but 86% of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/ul), and CD4+ lymphocyte count (>653/ul) predicted humoral vaccine response (area under the curve [AUC]: 62% [CI 56-78], 67% [CI 58-80] and 67% [CI 54-79], (positive predictive value [PPV]: 0.76, 0.7 and 0.71). Conclusion This study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

scholarly journals Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma

2021 ◽  
Vol 5 (16) ◽  
pp. 3053-3061
Author(s):  
C. Perry ◽  
E. Luttwak ◽  
R. Balaban ◽  
G. Shefer ◽  
M. M. Morales ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Messenger Rna ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Response Rates ◽  
Serological Response ◽  
Healthy Controls ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Abstract Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)–based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi &gt;6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P &lt; .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/μL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

scholarly journals Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients

2021 ◽  
Vol 5 (12) ◽  
pp. 2624-2643
Author(s):  
Abi Vijenthira ◽  
Inna Gong ◽  
Stephen D. Betschel ◽  
Matthew Cheung ◽  
Lisa K. Hicks
Keyword(s):  
Systematic Review ◽  
Influenza Vaccine ◽  
Pandemic Influenza ◽  
Hematologic Malignancy ◽  
Meta Analysis ◽  
Vaccine Dose ◽  
Hematologic Malignancies ◽  
Healthy Controls ◽  
Vaccine Response ◽  
Anti Cd20

Abstract The objective of this study was to perform a systematic review of the literature on vaccine responsiveness in patients who have received anti-CD20 therapy. PubMed and EMBASE were searched up to 4 January 2021 to identify studies of vaccine immunogenicity in patients treated with anti-CD20 therapy, including patients with hematologic malignancy or autoimmune disease. The primary outcomes were seroprotection (SP), seroconversion (SC), and/or seroresponse rates for each type of vaccine reported. As the pandemic influenza vaccine (2009 H1N1) has standardized definitions for SP and SC, and represented a novel primary antigen similar to the COVID-19 vaccine, meta-analysis was conducted for SC of studies of this vaccine. Pooled estimates, relative benefit ratios (RBs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-eight studies (905 patients treated with anti-CD20 therapy) were included (19 studies of patients with hematologic malignancies). Patients on active (&lt;3 months since last dose) anti-CD20 therapy had poor responses to all types of vaccines. The pooled estimate for SC after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%), with an RB of 0.05 (95% CI, 0-0.73) compared with healthy controls and 0.22 (95% CI, 0.09-0.56) compared with disease controls. SC compared with controls seems abrogated for at least 6 months following treatment (3-6 months post anti-CD20 therapy with an RB of 0.50 [95% CI, 0.24-1.06] compared with healthy and of 0.44 [95% CI, 0.23-0.84] compared with disease controls). For all vaccine types, response to vaccination improves incrementally over time, but may not reach the level of healthy controls even 12 months after therapy.

Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

2021 ◽  
pp. 135245852110033
Author(s):  
Quentin Howlett-Prieto ◽  
Xuan Feng ◽  
John F Kramer ◽  
Kevin J Kramer ◽  
Timothy W Houston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
B Cell ◽  
Regulatory T Cell ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Long Term Treatment ◽  
Anti Cd20

Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients. Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry. Results: CD8+ CD28− regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4+ FOXP3+ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8+ CD28− and CD4+ FOXP3+ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls. Interpretation: Long-term treatment with ocrelizumab markedly enriches CD8+ CD28− regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4+ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.

Vaccine Response In Recipients of HLA Mismatched Unrelated Double Unit Cord Blood Transplantation (CBT).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1247-1247 ◽  
Author(s):  
Trudy N Small ◽  
Christine Scura Iovino ◽  
Michelle Abboud ◽  
Marissa Lubin ◽  
Esperanza Papadopoulos ◽  
...  
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Optimal Schedule ◽  
High Dose ◽  
Vaccine Response ◽  
Post Transplant ◽  
History Of

Abstract Abstract 1247 The use of CBT has increased steadily over the last decade, with recent studies showing long-term progression-free survival similar to that of unrelated volunteer donor transplant recipients. The ability of CBT survivors to respond to post-transplant immunizations may differ from other allogeneic transplant populations due to the lack of transfer of memory T- and B-cells with the graft. Limited data have been reported on vaccine responses following this treatment modality. We, therefore, analyzed responses to immunizations in 23 double-unit CB recipients (17 adults, 6 children) transplanted at our center from 10/05-12/08. Patients were transplanted at a median age of 34 years (range 7–61) for the treatment of acute leukemia (n=13), or lymphoma/CLL (n=8/2). They received high-dose myeloablative (n=11), reduced intensity myeloablative (n=5), or non-myeloablative (n=7) conditioning according to diagnosis, age, prior therapy, and co-morbidities. GVHD prophylaxis consisted of a calcineurin inhibitor and mycophenolate mofetil. No patient received ATG. The study patients had sustained engraftment with a 5/6 (n=12) or 4/6 (n=11) HLA-matched unit. Seven recipients received rituximab (median 4 doses, range: 4–8) as planned post-transplant therapy for B-cell malignancies (n=6) or treatment of an autoimmune hemolytic anemia (n=1). Eleven patients had a history of grade II-IV acute GVHD and 5 had ongoing late acute or chronic GVHD prior to vaccination. Criteria for vaccination were: CD4 cell count of at least 200 cells/ul, PHA of greater than 60% lower limit of normal and serum IgG level >500 mg/dl at least 6 weeks following the last dose of IVIG. The median time to vaccination was 1.26 years post-CBT; this time was significantly longer in patients treated with Rituximab compared to those who were not (1.6 years versus 1.2 years, p=0.02), due to delayed normalization of B-cell numbers in the former group (449 days vs 108 days, p=0.004).Pre-vaccination titers obtained at a median of 1 year post-CBT demonstrated that over 85% of patients lacked protection against Pneumococcus, H. influenzae, and Pertussis, and at least 50% lacked immunity against tetanus, measles, and mumps. Seroconversion or >3- fold rise in titer was observed in response to tetanus, diphtheria, H. influenzae, and Pneumococcus in 90% (18/20), 81% (13/16), 80% (16/20)and 90% (18/20) of patients and was not significantly different in patients with or without a history of acute or chronic GVHD. Whereas 90% (5/6) of patients without a history of GVHD responded to a series of Hepatitis B immunizations, only 22% (2/9) of those with prior acute and/or chronic GVHD did so (p=0.03). No patient was protected against pertussis following a single TDaP (n=14) and only 1 of 5 patients responded to the protein conjugated meningococcal vaccine. Immunization with a live attenuated vaccine was initiated in 7 seronegative patients, including all 6 children, at a median of 2.25 years (range 1.5–3.6) post-CBT (MMR, n=7, Varivax, n=3). Seroconversion against measles, mumps, rubella, or chickenpox was observed in 3/7, 2/7, 6/7, and 1/3 patients, respectively. There were no serious reactions to any vaccine. These data suggest that CBT recipients are capable of responding to tetanus, diphtheria, H. Influenza and pneumococcal vaccines similar to other transplant groups. Nonetheless, the sub-optimal response to pathogens associated with outbreaks in the community (Hepatitis B, Pertussis, meningococcus, measles, mumps, varicella) highlight the need to obtain pre- and post-vaccination titers to document response, as well as define the optimal schedule of post-transplant immunizations specifically in this transplant population. Disclosures: No relevant conflicts of interest to declare.

Antibody Therapy in Aggressive Lymphomas

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 257-264 ◽  
Author(s):  
Thomas M. Habermann
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Natural History ◽  
B Cell ◽  
Antibody Therapy ◽  
Lymphoproliferative Disorders ◽  
Monoclonal Antibody Therapy ◽  
Aggressive Lymphomas ◽  
History Of ◽  
Anti Cd20

AbstractThe aggressive lymphomas are potentially curable. The natural history of certain aggressive lymphomas has been altered by monoclonal antibody therapy. Targeted monoclonal antibody therapy to the CD20 antigen has altered the outcome of patients with diffuse large B-cell lymphoma in patients of all ages. Anti-CD20–based radioimmunoconjugates are being evaluated as radioimmunotherapy approaches in patients who have relapsed and in stem cell transplant settings. Antibody-directed therapy to the B-cell–specific antigen CD22 are ongoing. New approaches include different CD20 antibodies and an antibody to the CD40 antigen, which is a member of the tumor necrosis factor (TNF) receptor family, which is expressed on B-cells. Antibody therapy has been incorporated into CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) therapy and other regimens such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and HyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone). Single-agent anti-CD20 therapy is active in the post-transplantation lymphoproliferative disorders. T-cell antibodies are under evaluation in a number of T-cell lymphoproliferative disorders. Targeted therapy has changed the natural history of a number of aggressive non-Hodgkin lymphomas. This review will describe the contributions of antibody therapies to the treatment of these diseases.

scholarly journals Rituximab in the treatment of multiple sclerosis in the Hospital District of Southwest Finland

2020 ◽  
Author(s):  
Laura Airas ◽  
Marjo Nylund ◽  
Iina Mannonen ◽  
Markus Matilainen ◽  
Marcus Sucksdorff ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cell ◽  
University Hospital ◽  
Health Care Environment ◽  
Care Environment ◽  
Serious Adverse Event ◽  
Hospital District ◽  
Disease Subtype ◽  
Cell Counts ◽  
Anti Cd20

AbstractBackgroundThere are already numerous B-cell depleting monoclonal anti-CD20 antibodies which have been used to reduce the inflammatory burden associated with multiple sclerosis (MS). We describe here our experience of treating MS-patients with B-cell depleting rituximab.Patients and methodsAll MS-patients (n=72) who had received rituximab treatment for at least six months by January 2019 were identified from the patient charts at the Turku University Hospital. Information about MS disease subtype, disease severity, MR-imaging outcomes and B-cell counts were collected from the charts.ResultsRituximab was well received and well tolerated by the patients. There were no serious infusion-related side effects. The most serious adverse event that led to treatment discontinuation was neutropenia. Our study confirms the usability of rituximab treatment for MS in the Finnish health care environment.ConclusionsOff-label rituximab-treatment can be successfully used to reduce MS disease burden for the benefit of MS patients.

scholarly journals Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

2021 ◽  
Author(s):  
Marie I. Samanovic ◽  
Amber R. Cornelius ◽  
Sophie L. Gray-Gaillard ◽  
Joseph Richard Allen ◽  
Trishala Karmacharya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
Prior History ◽  
Vaccine Candidates ◽  
Antibody Secreting Cell ◽  
Cell Responses ◽  
Efficacy Trials ◽  
History Of ◽  
Humoral Responses

ABSTRACTThe use of COVID-19 vaccines will play a major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccine candidates have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccine candidates differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 13 adults who recovered from COVID-19, compared to 19 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 T cell responses in both cohorts. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine for the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19.One Sentence SummaryPrior history of COVID-19 affects adaptive immune responses to mRNA vaccination.

scholarly journals Vaccine Hesitancy in Patients With Multiple Sclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. e991
Author(s):  
Lara Diem ◽  
Christoph Friedli ◽  
Andrew Chan ◽  
Anke Salmen ◽  
Robert Hoepner
Keyword(s):  
Multiple Sclerosis ◽  
Pneumococcal Vaccination ◽  
Standard Of Care ◽  
University Hospital ◽  
Vaccine Hesitancy ◽  
Public Health Issue ◽  
Future Research ◽  
Medical Chart Review ◽  
History Of ◽  
Anti Cd20

ObjectiveVaccine hesitancy is a complex public health issue referring to concerns about safety, efficacy, or need for vaccination. Using pneumococcal vaccination, which is recommend in anti-CD20–treated multiple sclerosis (MS) patients, as a model, we assessed vaccination behavior in patients with MS to prepare for the upcoming SARS-CoV-2 vaccination challenge.MethodsBy a medical chart review, we retrospectively identified patients with MS treated with ocrelizumab at the University Hospital Bern in 2018–2020. Pneumococcal vaccination was discussed with the patients during clinical visits and highlighted in the after-visit summary addressed to the general practitioner before ocrelizumab initiation as part of our clinical standard of care.ResultsPneumococcal vaccination was performed in 71/121 (58.7%) of patients, and 50/121 (41.3%) patients were not vaccinated. Patients who did not get a pneumococcal vaccination were younger (no vaccination vs vaccination; mean [95% CI] 40.1 [36.1–44.1] vs 45.4 [41.9–48.8], p = 0.028) and had more frequently a relapsing remitting disease course (no vaccination vs vaccination, n [%]; 43/50 [86.0%] vs 49/71 [69.0%], p = 0.031). Furthermore, patients who did not get vaccination had more frequently a history of comorbid psychiatric disorder (no vaccination vs vaccination, n (%); 12/50 [24.0] vs 7/71 [9.8], p = 0.035).ConclusionOur study demonstrated that in our single-center cohort, 41.3% of patients with MS do not get the recommended pneumococcal vaccination. Future research should focus on vaccine hesitancy in the vulnerable cohort of patients with MS to improve the safety of MS immunotherapies.

Antidepressant Medication May Moderate the Effect of Depression Duration on Hippocampus Volume

2016 ◽  
Vol 30 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Mark A. Rogers ◽  
Hidenori Yamasue ◽  
Kiyoto Kasai
Keyword(s):  
Major Depression ◽  
Antidepressant Treatment ◽  
Antidepressant Medication ◽  
Healthy Controls ◽  
Detailed History ◽  
Treatment History ◽  
Left Hippocampus ◽  
History Of ◽  
History Of Depression ◽  
Hippocampus Volume

Abstract. Hippocampus volume has been frequently, but not universally reported to be reduced in people with major depression relative to age-matched healthy controls. Among the potential reasons for this discrepancy in finding across studies is the effect of antidepressant medication. Hippocampus volume was determined by MRI (1.5 Tesla) for 10 people diagnosed with major depression for who detailed history of depression and antidepressant treatment history were known, and 10 age-matched healthy controls with no history of depression. Left, but not right, hippocampus volumes were significantly smaller in the patient group compared to the controls. Furthermore, there was a significant correlation such that left hippocampus volume was smaller with increasing lifetime duration of depression. However, this relationship was moderated by a significant correlation such that greater lifetime duration of antidepressant medication was associated with larger left hippocampus volume. The findings support the contention that antidepressant medication may act to normalize hippocampus volume.

scholarly journals Longitudinal analysis of antibody trajectories and humoral responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy (RituxiVac 2.0)

2021 ◽  
Author(s):  
Daniel Sidler ◽  
Alexander Born ◽  
Simeon Schietzel ◽  
Michael P. Horn ◽  
Daniel Aeberli ◽  
...  
Keyword(s):  
B Cell ◽  
Healthy Volunteers ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Decay Rates ◽  
Igg Antibodies ◽  
Link Type ◽  
Anti Cd20 ◽  
Humoral Responses

Background Morbidity and mortality of COVID-19 is increased in patients with B-cell depleting therapies, the majority of which also show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 antibodies in patients from the original RituxiVac study compared to healthy volunteers and investigate the immunogenicity of a third vaccination in previously non-responding patients. Methods A follow-up evaluation was performed in volunteers and patients from the RituxiVac Study (NCT04877496), which investigated the humoral and cell-mediated immune response after SARS-CoV-2 mRNA vaccination in patients with a history with anti-CD20 depleting therapies (rituximab or ocrelizumab). The current population included 33 patients and 26 healthy volunteers with initial humoral vaccine response and 32 non-responding patients. Primary outcome was anti-SARS-CoV-2 antibody trajectories in vaccine responders 4.3 months (median; interquartile range [IQR]: 3.6-4.8 months) after first evaluation and humoral responses after a third vaccine dose in previous non-responders. Antibody decay rates were compared using analysis of covariance in linear regression. Results In patients with detectable anti-spike IgG antibodies after two-dose vaccination, circulating anti-spike IgG persisted in 88% (29/33) of patients 5.6 months after the second vaccination (median; IQR: 5.1-6.7) compared to 92% (24/26) of healthy volunteers 6.8 months after the second dose (IQR: 6.0-7.1) (p=0.7). Antibody decay rates were comparable between patients and controls with -0.54 signal/cut-off (s/c) units per month (IQR -0.72 to -0.45) and -0.60 s/c units per month (IQR: -0.88 to -0.44), p=0.70. Two-dose responders with loss of circulating antibodies at follow-up (n=4/33, 12%) had lower initial antibody concentrations (p<0.01). Biomarkers for immunocompetence, including CD3, CD4 or CD19 cell count at baseline did not predict anti-spike IgG persistence. In two-dose non-responders, a third dose of mRNA vaccine against SARS-CoV-2 elicited humoral response with detectable anti-spike IgG antibodies in 19% (6/32) participants. No clinical parameters nor biomarkers of immunocompetence predicted humoral response after a third vaccine dose. Conclusion The present study reveals comparable antibody reduction rates between patients with CD20-depleting treatment history and healthy volunteers, but inefficient humoral responses to a third dose of SARS-CoV-2 mRNA vaccines in the majority of two-dose non-responders. There is a need for individually tailored vaccination strategies in immunocompromised patients that could be stratified by B cell counts and initial level of antibody titers. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

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