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Introduction: COVID-19 related encephalitis has been reported in pediatric patients;however, there are no reports in patients with inborn errors of immunity (IEI). Activated PI3K Delta Syndrome (APDS) is a disease of immune dysregulation with immunodeficiency, autoimmunity, and abnormal lymphoproliferation resulting from autosomal dominant gain-offunction variants in PIK3CD or PIK3R1 genes. We investigate a family with APDS, one mother and three children, one of whom developed COVID-19 related encephalitis. Method(s): Patients were consented to an IRB-approved protocol at our institution. Medical records and detailed immunophenotyping were reviewed. Family members were sequenced for IEI with a targeted gene panel. Result(s): The index case is a 10-year-old female with a known pathogenic variant in PIK3CD (c.3061 G > A, p.Glu1021Lys), who contracted SARS-COV-2 despite one COVID-19 vaccination in the series. Her disease course included COVID-related encephalitis with cerebellitis and compression of the pons, resulting in lasting truncal ataxia and cerebellar mutism. At that time, the patient was not on immunoglobulin replacement therapy (IgRT), but was receiving Sirolimus. Besides the index case, 3 family members (2 brothers, 1 mother) also share the same PIK3CD variant with variable clinical and immunological phenotypes. All children exhibited high transitional B-cells, consistent with developmental block to follicular B cell stage. Increased non-class switched IgM+ memory B cells and skewing towards CD21lo B cell subset, which is considered autoreactive-like, was observed in all patients. Of note, the patient had low plasmablasts, but normal immunoglobulins. Of her family members, only one was receiving both sirolimus and IgRT. Conclusion(s): We describe a rare case of COVID-19-related encephalitis in a patient with inborn error of immunity while not on IgRT. This may indicate infection susceptibility because of a lack of sufficient immunity to SARS-CoV-2, unlike the rest of her family with the same PIK3CD variant.Copyright © 2023 Elsevier Inc.
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Background Checkpoint inhibitor (CI) therapy has revolutionized the therapy landscape of NSCLC. However, why some patients do not respond to CI therapy remains unknown. The correlation between intra-tumoral B cell follicles and response to CI therapy has been established. B cell follicles within the lymph node become more dispersed with age and CD27-IgD- B cells (DNBc) are described to be age-associated. Moreover, DNBc are abundant in chronic infection, elderly, long COVID and auto-immunity and are described to be anergic and exhausted and often lack expression of CD21. DNBc are expanded in NSCLC tumors compared to healthy lung tissue and inversely correlate to switched memory B cells in the tumor. In this study we explored if there is a correlation between this B cell subtype in peripheral blood of NSCLC patients and response to CI therapy. Methods Patients treated with CIs within the Erasmus Medical Center were included in a prospective observational immunomonitoring study. Nineteen NSCLC patients treated with either Pembrolizumab (Pem) or Nivolumab and 5 healthy controls (HC) were selected. Pem was given in 6/11 responding patients (R) and 5/8 non-responding patients (NR). Peripheral blood mononuclear cells (PBMC) were collected before start of treatment and characterized by multicolor flow cytometry. Results HC and R showed a similar pattern in most B cell subsets. NR had significantly lower proportion of B cells within the PBMC fraction than Rand HC (R: 7.14%, NR: 2.91%, HC: 10.60%). In addition, NR had a significantly higher frequency of DNBc than R and HC (R: 9.43%, NR: 23.78%, HC: 7.19%) and there was no correlation between age and DNBc. The frequency of DNBc correlated positively with lack of CD21 expression (r2: 0.83) and expression of Ki67 (r2: 0.54) both in NR, Rand HC. The frequency of Ki67+CD21-DNBc within the B cell fraction was higher in NR than in R and HC (NR: 18.34%, R: 3.51%, HC: 0.67%). Conclusions We are the first to describe that frequencies of DNBc are higher in NR compared to R and HC. Specifically, Ki67+CD21-DNBc are increased in NR and might reflect an anergic, exhausted B cell phenotype. The absence of a correlation between age and DNBc could suggest that the increase in DNBc is induced by the tumor. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure D. Dumoulin: Financial Interests, Personal, Other: Roche, BMS, MSD, AstraZeneca, Novartis. J.G. Aerts: Financial Interests, Personal, Research Grant: Amphera, Roche, Eli Lilly;Financial Interests, Personal, Advisory Board: Amphera, Bristol-Myers Squibb, Eli Lilly, MSD, Roche;Financial Interests, Personal, Ownership Interest: Amphera;Financial Interests, Personal, Other: Takeda. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Background Cell-specific transduction remains one of the next frontiers for virally-delivered gene therapy. Efforts to achieve cell-specific transduction have largely been limited to borrowing of preexisting viral glycoproteins and pseudotyping viral surface envelopes to result in altered tropism. VSVG is derived from vesicular stomatitis virus (VSV) and is one of the most commonly used lentiviral (LV) pseudotype glycoproteins as its cognate receptor (LDLR) is present on nearly all dividing and non-dividing cells, enabling broad tropism of VSVG-pseudotyped LVs. Methods Our lab recently developed a receptor-blinded version of VSVG, in which point mutations (K47Q, R354A) of this glycoprotein results in a mutated VSVG with inability to bind and infect LDLR-expressing cells. This mutant viral glycoprotein, which we call VSVGmut, thereby loses its broad tropism, but critically retains its fusogen ability, enabling codisplay of a new LV pseudotype ligand to drive LV tropism. Results Initial experiments displaying high-affinity anti-CD19 scFvs alongside VSVGmut on the LV surface demonstrated infection of CD19+, but not CD19- cells. Subsequent work using endogenous ligands (CD80), Fabs (a-CD3e), cytokines (IL-13), viral glycoproteins (SARS-CoV-2 RBD), and peptide MHCs (pMHCs) revealed the modularity of this platform for achieving potent transduction of on-target cells, with minimal infection of bystander cells, across a range of affinities (pM to uM) and at frequencies as low as 1 in 100,000. This technology allowed for library on library screening of 96 viral pMHC-displaying LVs against a repertoire of >450,000 TCRs in pool, which accurately uncovered EBV- and Flu-specific TCRs through scRNA sequencing. Conclusions The VSVGmut platform has resulted in our lab's ability to pair pMHCs with cognate TCRs and viral surface antigens with cognate BCRs, in addition to achieving lineagespecific transduction of T and B cell subsets, setting the stage for cell-specific gene therapy.
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Introduction: Cladribine is a CNS penetrant disease-modifying treatment, which - in an oral preparation (Mavenclad) - was licensed for people with highly active relapsing MS in August 2017. Our experience with cladribine dates back to 2014 when we started using subcutaneously injected cladribine as a compassionate immunotherapy in people with MS (pwMS) off-label. This programme enabled us to embed CLADRIPLAS, a mechanistic study of the effect on intrathecal B cell and plasma cell function and axonal damage focussing on progressive MS (PMS) (IRAS # 240360). Objective(s): To study the effect of cladribine on peripheral and intrathecal B and plasma cells. Aim(s): To study the effect of cladribine on oligo-clonal bands (OCB) and the level of neurofilament light (NfL) chain. Method(s): Observational study involving two lumbar punctures and phlebotomies, 6-12 months apart, to collect B cell subsets, and intrathecal plasma cell as well as neurofilament light chain (NfL) level in pwMS eligible and not eligible for cladribine treatment based on cerebro-spinal fluid (CSF) NfL, clinical and/or MRI evidence of inflammatory disease activity. Here, we report baseline cohort characteristics. Result(s): Thirty-eight pwMS were recruited (19 women, 19 men) and had their first sample collections. Eight pwMS were eligible for cladribine treatment (7 based on elevated NfL, 1 due to MRI activity). Follow-up samples have been collected in 21. Mean age at baseline was 55 years (40-76). Fourteen had primary, 24 secondary PMS. Median EDSS=6.5 (3.5-8). Twenty-one pwMS had been treated with DMT before consideration of cladribine, 17 were immunotherapy-naive. Mean CSF-NfL level was 552 (176- 2072) pg/ml. Conclusion(s): Despite restrictions due to COVID-19, 38 of 40 planned pwMS were enrolled. 7/8 were eligible based on CSFNfL level indicating the importance of using biomarkers other than MRI to establish disease activity in PMS. We expect our cohort to enable meaningful comparison between groups. CLADRIPLAS will finish in early 2023.
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Background: Vaccination against SARS-CoV-2 is a potent preventive tool against Covid-19. However, response to vaccination vary depending on comorbidities. This study evaluates clinical and immunological factors affecting humoral response of End-Stage Renal Disease(ESRD) patients to BNT162b2 Vaccine. Method(s): Humoral immunity was evaluated in 54 ESRD patients, by serum levels of anti-receptor-binding-domain (RBD) and neutralizing antibodies (Nab), measured by CLIA, 30 (T1), 60 (T2) and 120 (T3) days, after the second vaccine dose. Results were correlated to baseline patients' T and B-lymphocyte subpopulations as determined by flow cytometry. Result(s): Proportion of seroconverted patients based on Nab titer was diminished from 83.3%(T1) to 53.7%(T3), in three months. Age was negatively correlated to Nab at T1 and T2 (T1:R=-0.334, p=0.027, T2:R=-0.344, p=0.022). Patients on hemodiafiltration had higher Nab titers at T3. Presence of diabetes was associated with lower response rate, as 9/11 diabetics compared to 16/43 non-diabetics lost seroconversion at T3. Univariate analysis revealed a strong positive correlation of naive CD4 T-lymphocyte population with RBD at T1(R2=0.199, p=0.015) and with Nab titer at T3(R2=0.645, p<0.001), while no association was shown with naive CD8 T-lymphocytes. Nab titers at T3 were significantly correlated with late differentiated CD4 T-lymphocytes(R2=0.56, p<0.001) and EMRA CD8 T-lymphocytes(R2=0.156, p=0.017). Finally, RBD levels had a significant positive correlation with naive, and negative with memory B-lymphocyte count at T3(R2=0.147, p=0.031, R2=0.159, p=0.039, respectively). Conclusion(s): Age, diabetes mellitus and hemodialysis prescription have a strong impact to response to vaccination. T and B-lymphocytes phenotype are major determinants of humoral response potency to COVID vaccination with BNT162b2, in ESRD patients.
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Background: Infectious complications are a major cause of morbidity and mortality in Chronic Lymphocytic Leukaemia (CLL). Therapeutic approaches that deplete CLL cells also affect normal B-cells. Optimal treatment would result in eradication of CLL cells and recovery of normal immune function. FLAIR (ISRCTN01844152) is a phase III trial for previously untreated CLL comparing ibrutinib plus rituximab (IR) with fludarabine, cyclophosphamide and rituximab (FCR) and subsequently amended to also compare ibrutinib plus venetoclax (I+V) and ibrutinib alone (I) with FCR. Measurable residual disease (MRD) and normal B-cell levels were assessed at multiple timepoints. Aims: To assess the depletion of normal B-cells during treatment and recovery after end of treatment. Methods: Participants aged under 75 years with <20% TP53-deleted cells were initially randomised to FCR or IR and subsequently to FCR, IR, I+V or I with the IR arm closed after randomisation of 771 participants to FCR/IR. FCR was given for 6 cycles, while treatment in the IR, I and I+V arms continued for up to 6 years except in participants attaining <0.01% MRD who continued treatment for the time taken to achieved MRD <0.01% and then stopped if MRD remained <0.01%. Month (M) 24 was earliest permitted stopping point. MRD flow cytometry was performed according to ERIC guidelines (panel: CD19/5/20/43/79/81+ROR1, acquisition of 0.5-2.2 million cells, BD Biosciences Lyric). Additional analysis of normal B-cell subsets was performed in a cohort of >500 patients (panel: CD19 to identify B-cells, CD20/5/79b+ROR1 and CD3 to exclude CLL & contaminating cells, with CD27/ 38/IgD/IgM to characterise normal B-cell subsets using a Coulter Cytoflex LX). Results: Normal B-cells were undetectable during FCR treatment and only rarely detectable until 12 months after last FCR cycle. Circulating normal B-cells were reduced in number or undetectable in participants receiving ibrutinibcontaining regimens with greater depletion in the I+V and IR arms relative to I monotherapy. B-progenitors persist through FCR treatment but were depleted during I, I+R or I+V treatment. Normal B-cell levels at 24 and 36 months after randomisation, with time off-treatment if applicable, are shown in Figure 1. In the ibrutinib-containing arms (IR, I, and I+V), there was a trend towards fewer COVID-associated SAE at any time point for participants with detectable B-cells at 24M (4/181, 2.2%) compared to those with no detectable B-cells (14/344, 4.1%) and COVID-associated SAEs were not observed in FCR-treated participants who had recovered any level of normal B-cells by 24M (0/215). However, the data on COVID infections are limited and there was no apparent association between normal B-cell levels at 24M with the proportion of participants experiencing an infectious SAE overall. Assessment of normal B-cell subsets during ibrutinib-based treatment demonstrated a mix of naïve and memory B-cells. Serological response to COVID infection/vaccination in this cohort is currently being performed. Participants stopping I+V treatment at 24-30 months post-randomisation due to MRD eradication showed rapid recovery of normal naive B-cells within 6-12 months after end of treatment in the vast majority (>95%) of evaluable cases. Summary/Conclusion: Normal circulating B-cells are depleted during treatment with rituximab but can persist at a low level during I, IR or I+V treatment. Most patients in remission after treatment with FCR or I+V show recovery of normal B-cells at 12 months of stopping treatment.
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Background: Rheumatic musculoskeletal diseases (RMD) are pathological conditions characterized by an impaired immunological system that is determinant both in the pathogenesis and in the inadequate response to infections. The use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) or biologic and targeted synthetic (b/ts) DMARDs, contribute to compromise immunological reactivity. Objectives: To analyze the immune response to SARS-CoV-2 in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving treatment with DMARDs and to investigate the effect of the different classes of drugs on humoral and cellular response. Methods: Patients were tested for anti-SARS-CoV-2 IgG, IgM and IgA antibodies to nucleoprotein (N) and receptor-binding domain (RBD) through ELISA and neutralization assays. Then, we performed a fow cytometry analysis of monocytes, NK cells, B and T lymphocytes from PBMCs of serologically positive patients. We also included a cohort of non-RMD individuals recovered from COVID-19 as a reference group of non-immunosuppressed subjects. A frst recruitment occurred in May-June 2020 (T1) and a second recruitment, 3-4 months after (T2), allowed to evaluate the persistence of the antibody response over time and to investigate the cellular immune response to SARS-CoV-2 in RMD patients having resolved the infection. Results: During T1, 358 patients with RA (n=200) or SpA (n=158) were recruited. Mean age was 52.8, 64% were female. All patients were treated with DMARDs, 299 with b/tsDMARDs and 59 received csDMARDs alone. One third was also receiving corticosteroids (CS). At T2, 36 subjects were recruited. We found a seroprevalence rate of 18.4%, which did not signifcantly differ between RA and SpA groups, and between patients treated with b/ts-DMARD or csDMARDs, either alone or in combination with CS (Table 1). Antibody levels of RMD patients were lower than non-RMD individuals (Figure 1), with CTLA4-Ig-treated patients having the lowest IgG levels. This difference was less marked in symptomatic RMD patients. 72% of seropositive patients elicited neutralizing sera. Despite an overall decrease in anti-RBD and anti-N titers, more than two-third of patients maintained antibodies titers above positivity threshold at T2. Concerning cellular response, we found that CD8+ T-cells frequency was overall comparable between RMD and non-RMD convalescents, and did not differ in b-or cs-DMARD treated ones. Conversely, CD4+ T-cell frequencies were signifcantly lower in RMD patients, especially those treated with anti-IL6R and CTLA4-Ig. B-cell subpopulations (class-switched, memory, and IgG+ memory B-cells) had sustained frequencies in anti-TNFα treated patients, while they had a trend of reduction in patients treated with anti-IL6R and CTLA4-Ig. Conclusion: Our data provide a comprehensive picture of the humoral and cellular immune responses to SARS-CoV-2 infection in RMD patients. We showed that DMARDs treatments did not alter a successful antibody response to the virus and did not hamper the antibody neutralizing ability. However, the magnitude of antibody response was slightly reduced compared to non-RMD individuals, especially in patients receiving CTLA4-Ig. We did not observe marked differences in the B-and T-cell populations between RMD patients compared to non-RMD individuals. However, in patients receiving anti-TNFα we found a higher relative abundance of effector adaptive population compared to other bDMARDs.
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Background: Vaccination is considered efficient in controlling infections incl. SARS-CoV-2. Prior studies showed that patients receiving rituximab (RTX) with low B cell counts are at increased infectious risk (1) and risk of inadequate vaccination responses (2, 3). Thus, the ability to further defne and predict vaccination responses in these patients may guide their optimal protection. Objectives: To assess predictive biomarkers of vaccination responses upon SARS-CoV-2 vaccination in RTX treated patients. Methods: B cell characteristics before vaccination were evaluated to predict responses in 15 patients with autoimmune infammatory rheumatic diseases receiving RTX. 11 patients with rheumatoid arthritis on other therapies (RA), 11 kidney transplant recipients (KTR) and 15 healthy volunteers (HC) served as controls. A multidimensional analysis of B cell subsets and a correlation matrix were performed to identify predictive biomarkers. Results: Signifcant differences regarding absolute B cell counts and specifc subset distribution pattern between the groups were validated at baseline. Here, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) comprised naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells (Figure 1). Moreover, there was a positive correlation between neutralizing antibodies and absolute B cell numbers with B cells expressing HLA-DR and CXCR5 (involved in antigen presentation and germinal center formation) as well as an inverse correlation with CD95 expression and CD21low expression (marker for activation and exhaustion) on B cells. Conclusion: Substantial repopulation of naïve B cells upon RTX therapy appears to be essential for an adequate vaccination response requiring germinal center formation. In contrast, expression of exhaustion markers (CD21low, CXCR5-, CD95+) indicate negative predictors of vaccination responses. These results may guide optimized vaccination strategies in RTX treated patients clearly requiring antigen-inexperienced B cells for appropriate protection.
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Introduction: Patients with hematologic malignancies are at an increased risk of morbid/mortality from COVID-19. Our prospective clinical study evaluated immune responses to COVID-19 mRNA vaccines in patients with B-cell lymphoma who had received CD19-directed chimeric antigen receptor (CAR) T cell therapy. Methods: We measured SARS-CoV-2 neutralizing activity of plasma from 18 patients and 4 healthy controls (HC) and antibody titers against viral spike proteins (S1, S2, RBD) including their delta variants using an enzyme-linked immunoassay (ELISA). We measured B cell subpopulations in the patients' blood using flow cytometry. Results: We found that the peripheral blood plasma from 3/4 HCs showed substantial SARS-CoV-2 neutralizing activity already at 4 weeks after the first dose of COVID-19 mRNA vaccine while none of the CD19 CART patients evidenced any antibody-mediated neutralizing activity at the same point in time. At 4 weeks after receiving the second dose of the vaccine, all 4 HCs showed complete neutralizing activity. In marked contrast, only 1 of 14 CART patients evidenced any relevant antibody-mediated SARS-CoV-2 neutralizing activity. Assessing whether a globally insufficient antibody-mediated immunity was the underlying cause of the lack of a response to the COVID-19 vaccine in our CART patients, we found that IgG antibody levels against common microbial and viral antigens like influenza, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and tetanus toxoid, were comparable to those observed in HCs. However, while at 4 weeks post second dose of the vaccine the HCs showed high levels of vaccine-induced IgG antibody titers against all the viral spike proteins (S1, S2, RBD), including the delta variants of the S1 and RBD proteins, the vast majority of our CART patients did not evidence any SARS-CoV-2-specific antibodies. Importantly, a third booster vaccination did not lead to an improvement in the antiviral immunity in the 4 CART patients analyzed. When we assessed B cell subpopulations in the blood of patients and HCs, we found that prior treatments had completely eradicated all CD19+/CD20+ B cells in the patients while numbers of long-lived memory plasma cells were comparable to those of HCs. Conclusions: In this study, 17 of 18 patients with lymphoma who received CD19 CART therapy had very poor immunoreactivity to 1-3 doses of mRNA-based COVID-19 vaccines. Importantly, antibody responses to common recall antigens were preserved, suggesting impaired immune response primarily against novel antigens like SARS-COV-2. This lack of immunoreactivity against novel antigens was probably based on the eradication of earlier-stage B cell subpopulations after treatment with anti-CD19 and anti-CD20 immunotherapies.
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The dominance of reliably immunized population is a fundamental factor in prevention of COVID-19 pandemia, with immune prophylaxis taking a dominant position. Due to lack of clear data on the intensity of specific immunity after a new coronavirus infection, consolidation of immunological memory by vaccination becomes the urgent task, in order to exclude the risk of re-involvement of previously ill patients into the epidemic process. Meanwhile, many questions related to vaccination of COVID-19 survivors do not get distinct answers. To study the features of immune response, using a vaccine based on SARS-CoV-2 peptide antigens (EpiVacCorona), we monitored 81 participants. The inclusion criteria were data confirming COVID-19 in the anamnesis (medical documentation), low levels or absence of antibodies to the SARS-CoV-2 nucleocapsid protein, and negative PCR tests for SARS-CoV-2. When assessing the data of post-vaccinal immunity checked 21 days after 1st dose of the vaccine, the patients were divided into 2 groups: those who did not respond, and those who developed the immune response. In order to identify possible reasons for different phenotypic patterns of humoral response to vaccination, a comparative analysis of B lymphocyte indexes was carried out in these groups. Absolute counts, subpopulation composition and activation potential of peripheral blood B lymphocytes were determined by flow cytofluorometry using appropriate labeled monoclonal antibodies purchased from Beсkman Coulter. Comparative analysis of B lymphocyte indexes on the day of first vaccination showed that the persons who did not respond to the vaccine had smaller counts of circulating B cells, i.e., both percentage and absolute cell numbers, than in comparison group, as well as changed ratio of B1-to-B2 subpopulations. After administration of the first vaccine dose (by day +21), in alternative variant of the antibody response to V1, the differences in the parameters of B cells were presented as a smaller percentage and absolute numbers of regulatory B lymphocytes in non-responding participants. Moreover, the contents of minor B cell subpopulations were decreased in the non-responding group than in the comparison group, thus affecting the values of the B1:B2 ratio. In general, the presented data demonstrate that the absence of secondary immune response to antigens of the SARS-CoV-2 peptide vaccine could be is associated with altered differentiation of B1 and B2 subpopulations, B regulatory lymphocytes, B memory cells.
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Background: Infections are a common cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Prolonged immune recovery post-HSCT increases the risk of infection and raises concern for poor response to vaccinations. Reimmunization is recommended for all pediatric HSCT patients by transplant and infectious disease organizations1,2, and individual institutions often develop revaccination guidelines. Objective: At Vanderbilt Children's Hospital (VCH), the clinical practice guideline (CPG) instituted in June 2015 recommends early initiation (6 months) of reimmunization in immunologically appropriate patients, starting with Haemophilus influenzae type B (Hib) and pneumococcal conjugate (PCV13) vaccinations. Therefore, we examined the feasibility of early vaccination for allogeneic HSCT patients and determined the causes of delayed or lack of vaccination. Methods:A retrospective chart review of the electronic medical record was conducted under an IRB-approved protocol. Data was gathered and entered in a REDCap database, including dates of vaccination, immune reconstitution studies (IgG concentration, T/B cell subsets) and clinical outcomes [e.g., intravenous immunoglobulin (IVIg) administration, graft versus host disease (GvHD), relapse] through 6-month (+/- 30 days) post-HSCT. Early revaccination was defined as Hib and PCV13 administration within 210 days post-HSCT. Patients not meeting this definition were further examined for factors that led to delay or lack of vaccinations. Patients were included if they were alive without underlying disease progression or graft failure 6-months post-HSCT. Results: Between June 15, 2015 and June 30, 2021, 66 patients met inclusion criteria. Early revaccination occurred in 21/66 patients (32%). Of the 45/66 (68%) that did not receive 6-month vaccinations, the most common reason was concern for impaired immune reconsti- tution (n = 33/45, 73%). Indicators of poor immune recovery included recent IVIg administration (n = 15), ongoing immunosuppression (n = 24), and poor B cell recovery (n = 4);many patients had multiple indications. Other reasons for delay included patient or parent refusal (n = 4), prioritization of COVID vaccinations (n = 3), scheduling conflicts (n = 4), and other (n = 1). Conclusions: Early vaccination occurred in 32% of patients. At 6 months post-HSCT, 50% of patients had poor immune reconstitution resulting in appropriate vaccination delays. However, scheduling conflicts and vaccine hesitancy despite eligibility were small but significant contributors, accounting for 17% of delays. This is a small, single center study but highlights significant challenges with delivery of best practice guidelines. Future directions could include engagement with other institutions regarding best practices to address vaccine hesitancy and to further explore if early revaccination reduces risk of infectious complications post-HSCT.
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Introduction. The pandemic caused by the SARS-CoV-2 virus is an important medical and social problem. It remains unclear the stability of the developed humoral immunity against the SARS-CoV-2 virus, the average duration of preservation of the titer of specific antibodies. The need to identify humoral mechanisms of immune defense in patients with COVID-19 determined the purpose of this study. The aim of the study – to evaluate the dynamics of changes in the content of specific IgG antibodies against various antigens of the SARS-CoV-2 virus and B-lymphocyte subpopulations throughout the year in people who have had COVID-19. Material and methods. The study included 90 patients who had undergone COVID-19 in various forms, subsequently divided into 2 groups: persons with asymptomatic and mild course (57 patients) and with moderate or severe course of the disease (33 patients). The dynamics of the concentration of specific antibodies to the SARS-CoV-2 virus was evaluated by enzyme immunoassay every 3 months for a year. The content of the total pool B-lymphocytes (naive B-lymphocytes, memory B-cells, regulatory B-lymphocytes) and various subpopulations was evaluated by flow cytofluorimetry. Results. When assessing the dynamics of IgG to the S-protein of the SARS-CoV-2 virus, their preservation was noted by the 12th month after recovery. In patients with severe and moderate COVID-19 forms, these indicators are significantly higher. More severe forms of COVID-19 are accompanied by significantly higher content level of memory B cells throughout the observation period. Conclusion. Moderate and severe forms of COVID-19 induce more persistent postinfectious humoral immunity, provided by an increase in memory B cells in comparison with lighter forms.