XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants (preprint)

The rapid emergence of divergent SARS-CoV-2 variants has led to an update of the COVID-19 booster vaccine to a monovalent version containing the XBB.1.5 spike. To determine the neutralization breadth following booster immunization, we collected blood samples from 24 individuals pre- and post-XBB.1.5 mRNA booster vaccination (~1 month). The XBB.1.5 booster improved both neutralizing activity against the ancestral SARS-CoV-2 strain (WA1) and the circulating Omicron variants, including EG.5.1, HK.3, HV.1, XBB.1.5 and JN.1. Relative to the pre-boost titers, the XBB.1.5 monovalent booster induced greater total IgG and IgG subclass binding, particular IgG4, to the XBB.1.5 spike as compared to the WA1 spike. We evaluated antigen-specific memory B cells (MBCs) using either spike or receptor binding domain (RBD) probes and found that the monovalent booster largely increases non-RBD cross-reactive MBCs. These data suggest that the XBB.1.5 monovalent booster induces cross-reactive antibodies that neutralize XBB.1.5 and related Omicron variants.

Computational detection of antigen specific B cell receptors following immunization (preprint)

B cell receptors (BCRs) play a crucial role in recognizing and fighting foreign antigens. High-throughput sequencing enables in-depth sampling of the BCRs repertoire after immunization. However, only a minor fraction of BCRs actively participate in any given infection. To what extent can we accurately identify antigen-specific sequences directly from BCRs repertoires? We present a computational method grounded on sequence similarity, aimed at identifying statistically significant responsive BCRs. This method leverages well-known characteristics of affinity maturation and expected diversity. We validate its effectiveness using longitudinally sampled human immune repertoire data following influenza vaccination and Sars-CoV-2 infections. We show that different lineages converge to the same responding CDR3, demonstrating convergent selection within an individual. The outcomes of this method hold promise for application in vaccine development, personalized medicine, and antibody-derived therapeutics.

Deep profiling of antigen-specific B cells from different pathogens identifies novel compartments in the IgG memory B cell and antibody-secreting cell lineages (preprint)

A better understanding of the bifurcation of human B cell differentiation into memory B cells (MBC) and antibody-secreting cells (ASC) and identification of MBC and ASC precursors is crucial to optimize vaccination strategies or block undesired antibody responses. To unravel the dynamics of antigen-induced B cell responses, we compared circulating B cells reactive to SARS-CoV-2 (Spike, RBD and Nucleocapsid) in COVID-19 convalescent individuals to B cells specific to Influenza-HA, RSV-F and TT, induced much longer ago. High-dimensional spectral flow cytometry indicated that the decision point between ASC- and MBC-formation lies in the CD43+CD71+IgG+ Activated B cell compartment, showing properties indicative of recent germinal center activity and recent antigen encounter. Within this Activated B cells compartment, CD86+ B cells exhibited close phenotypical similarity with ASC, while CD86- B cells were closely related to IgG+ MBCs. Additionally, different activation stages of the IgG+ MBC compartment could be further elucidated. The expression of CD73 and CD24, regulators of survival and cellular metabolic quiescence, discerned activated MBCs from resting MBCs. Activated MBCs (CD73-CD24lo) exhibited phenotypical similarities with CD86- IgG+ Activated B cells and were restricted to SARS-CoV-2 specificities, contrasting with the resting MBC compartment (CD73-/CD24hi) that exclusively encompassed antigen-specific B cells established long ago. Overall, these findings identify novel stages for IgG+ MBC and ASC formation and bring us closer in defining the decision point for MBC or ASC differentiation. ImportanceIn this study, researchers aimed to better understand human B cell differentiation and their role in establishing long-lived humoral immunity. Using high-dimensional flow cytometry, they studied B cells reactive to three SARS-CoV-2 antigens in individuals convalescent for COVID-19, and compared their phenotypes to B cells reactive to three distinct protein antigens derived from vaccines or viruses encountered months to decades before. Their findings showed that Activated B cells reflect recent germinal center graduates that may have diverse fates; with some feeding the pool of antibody-secreting cells and others fueling the resting memory B cell compartment. Activated B cells gradually differentiate into resting memory B cells through an activated MBC phase. Increased expression of the cellular metabolic regulators CD73 and CD24 in resting memory B cells distinguishes them from the activated memory B cells phase, and is likely involved in sustaining a durable memory of humoral immunity. These findings are crucial for the development of vaccines that provide lifelong protection and may show potential to define reactive B cells in diseases where the cognate-antigen is still unknown such as in autoimmunity, cancers, or novel viral outbreaks.

Memory B cells dominate the early antibody-secreting cell response to SARS-CoV-2 mRNA vaccination in naive individuals independently of their antibody affinity (preprint)

Memory B cells (MBCs) formed over the individual's lifetime constitute nearly half of the adult peripheral blood B cell repertoire in humans. To assess their response to novel antigens, we tracked the origin and followed the differentiation paths of MBCs in the early anti-S response to mRNA vaccination in SARS-CoV-2-naïve individuals on single-cell and monoclonal antibody level. Newly generated and pre-existing MBCs differed in their differentiation paths despite similar levels of SARS-CoV-2 and common corona virus S-reactivity. Pre-existing highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody secreting cells (ASCs). In contrast, newly generated MBCs derived from naïve precursors showed strong signs of antibody affinity maturation before differentiating into ASCs. Thus, although pre-existing human MBCs have an intrinsic propensity to differentiate into ASCs, the quality of the anti-S antibody and MBC response improved through the clonal selection and affinity maturation of naïve precursors.

SARS-CoV-2 shedding and evolution in immunocompromised hosts during the Omicron period: a multicenter prospective analysis (preprint)

Background: Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection and associated intrahost viral evolution remain unclear. Methods: Adults aged >18 years were enrolled at 5 hospitals and followed from 4/11/2022-2/1/2023. Eligible patients were SARS-CoV-2 positive in the previous 14 days and had a moderate or severely immunocompromising condition or treatment. Nasal specimens were tested by rRT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. Results: We enrolled 150 patients with: B cell malignancy or anti-B cell therapy (n=18), solid organ or hematopoietic stem cell transplant (SOT/HSCT) (n=59), AIDS (n=5), non-B cell malignancy (n=23), and autoimmune/autoinflammatory conditions (n=45). Thirty-eight (25%) were rRT-PCR positive and 12 (8%) were culture-positive [≥]21 days after initial SARS-CoV-2 detection or illness onset. Patients with B cell dysfunction had longer duration of rRT-PCR positivity compared to those with autoimmune/autoinflammatory conditions (aHR 0.32, 95% CI 0.15-0.64). Consensus (>50% frequency) spike mutations were identified in 5 individuals who were rRT-PCR positive >56 days; 61% were in the receptor-binding domain (RBD). Mutations shared by multiple individuals were rare (<5%) in global circulation.

The number of similar epitopes determines the longevity of immunological memory (preprint)

The half-life of specific antibodies against various antigens varies tremendously from a few months to over 10,000 years. The reasons are largely unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS) within each virus. Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of half-life was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunizationtreatments, –that is, for every additional EWSS, the half-life of the antibody would be doubled. After immunization, proportions of antigen-specific memory B cells (MBC) first increased and then decreased. In the descending phase, the antibody titers were positively correlated with the numbers of MBC. This study also discusses improvement measures for vaccines against other viruses.

Infectious complications following CAR-t cell therapy for B cell non-Hodgkin lymphoma: a single-center experience and review of the literature.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.

Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults (preprint)

Background: T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants. Method: We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human clinical trial and observed a favorable safety profile and induction of poly-specific T cell responses until month 3. Here, we report on long-term safety and efficacy data of CoVac-1 in healthy adults until month 12. Findings: CoVac-1 is well tolerated without long-term immune-related side effects and induces long-lasting anti-viral T cell responses in 100% of study participants. Potent expandability of CD4+ and CD8+ T cells targeting multiple different CoVac-1 T cell epitopes was observed 6 and 12 months after one single dose of CoVac-1. T cell responses were associated with the severity and the number of local adverse events at injection site. Beyond induction of T cell immunity, 89% of study participants developed CoVac-1-specific IgG antibody titers which associated with the intensity of the T cell response, indicating that CoVac-1-specific CD4+ T cells support the induction of B cell responses. Vaccination with approved COVID-19 vaccines boosted CoVac-1-specific T cell responses. Overall, a low SARS-CoV-2 infection rate was observed in the study population (8.3% of participants until month 12). Interpretation: Together, a single application of CoVac-1 elicits long-lived and broad SARS-CoV-2-specific T cell immunity, which further supports the current evaluation of our T cell activator in patients with congenital or acquired B cell defects (NCT04954469). Funding: This trial is funded by the Ministry of Science, Research and the Arts Baden-Wuerttemberg., Germany

Migratory Pneumonia in Prolonged SARS-CoV-2 Infection in Patients Treated With B-cell Depletion Therapies for B-cell Lymphoma.

OBJECTIVE: To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms. MATERIALS AND METHODS: From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37-71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features. RESULTS: All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, follow-up CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25. CONCLUSION: COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.

Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmaltrevir/ritonavir and tixegavimab/cilgavimab (preprint)

Background: Little data exists to guide the treatment of persistent COVID-19 in immunocompromised patients. We have employed a unique protocol combining tixegavimab/cilgavimab, and short-term combination antivirals including remdesivir. Methods: A retrospective single-center analysis of persistent COVID-19 in immunocompromised patients. Response was assessed by symptom resolution, declining C-reactive protein (CRP) levels and increasing SARS-CoV-2-PCR cycle-threshold (Ct) values. Results: Fourteen patients were included, including 2 kidney transplant recipients, 11 with B-cell lymphoproliferative disease, treated with anti-CD20 or ibrutinib, and 1 with rheumatoid arthritis, treated with anti-CD20. Median Ct-value was 27 (interquartile range (IQR):24-32). All patients received tixegavimab/cilgavimab and a 5-day course of remdesivir. Eleven also received nirmaltrevir/ritonavir and one received molnupiravir. Median follow-up was 45 days (IQR:12-89). Eleven patients had complete responses including symptom resolution, decrease in CRP, and increase in Ct values (all with either a negative PCR or Ct value>30 on day 4-16). Three patients had a partial response with relapses requiring re-admission. One had died, and two responded to prolonged antiviral treatments. Conclusions: A combination of monoclonal antibodies with antivirals has led to complete resolution of persistent COVID-19 in most severely-immunocompromised patients. Controlled studies will further direct the treatment of these patients, while more effective antivirals are urgently needed.

SARS-CoV-2 induced B cells generate an anticipatory memory against new virus variants and re-engage in COVID-19 vaccine responses (preprint)

During the COVID-19 pandemic, numerous new SARS-CoV-2 variants of concern (VOC) evolved, many of which escape from antibody responses. Vaccination of COVID-19 convalescent individuals induces antibody responses of superior quantity and quality, which may even neutralize new VOC. We analyzed memory B cells (MBC) from convalescent donors and studied their involvement in COVID-19 vaccine responses. By expressing monoclonal antibodies from immunoglobulin V(D)J sequences of MBC and reverting their somatic hypermutations (SHM) to germline codes, we found that antibody maturation is crucial for the cross-neutralization of VOC. Infection-induced MBC substantially contributed to the subsequent vaccine response. A few dominant clonotypes that used characteristic VH gene segments and that diversified through SHM constituted a large fraction of the responding B cells. Analysis of functional consequences revealed that certain SHM contribute to the formation of an anticipatory memory that is suitable to neutralize virus variants that might emerge in the future.

Comparing human and artificial intelligence in writing for health journals: an exploratory study (preprint)

Aim: and objectives: The aim was to contribute to the editorial principles on the possible use of Artificial Intelligence (AI)- based tools for scientific writing. The objectives included: A. Enlist the inclusion and exclusion criteria to test ChatGPT use in scientific writing B. Develop evaluation criteria to assess the quality of articles written by human authors and ChatGPT C. Compare prospectively written manuscripts by human authors and ChatGPT Design: Prospective exploratory study Intervention: Human authors and ChatGPT were asked to write short journal articles on three topics: 1) Promotion of early childhood development in Pakistan 2) Interventions to improve gender-responsive health services in low-and-middle-income countries, and 3) The pitfalls in risk communication for COVID-19. We content analyzed the articles using an evaluation matrix. Outcome measures: The completeness, credibility, and scientific content of an article. Completeness meant that structure (IMRaD) and organization was maintained. Credibility required that others work is duly cited, with an accurate bibliography. Scientific content required specificity, data accuracy, cohesion, inclusivity, confidentiality, limitations, readability, and time efficiency. Results: The articles by human authors scored better than ChatGPT in completeness and credibility. Similarly, human-written articles scored better for most of the items in scientific content except for time efficiency where ChatGPT scored better. The methods section was absent in ChatGPT articles, and a majority of references in its bibliography were unverifiable. Conclusions: ChatGPT generates content that is believable but may not be true. The creators of this powerful model must step up and provide solutions to manage its glitches and potential misuse. In parallel, the academic departments, editors, and publishers must expect a growing utilization of ChatGPT and similar tools. Disallowing ChatGPT as a co-author may not be enough on their part. They must adapt the editorial policies, use measures to detect AI-based writing, and stop its likely implications for human health and life.

Comprehensive Bioinformatics analysis of angiotensin-converting enzyme 2 (ACE2) (preprint)

ACE2, a member of the angiotensin converting enzyme family, plays an irreplaceable role in the renin-angiotensin system. And the variations of ACE2 are regarded as the key factor to human diseases such as the novel coronavirus pneumonia, cardiovascular disease, and tumors. Here, we summarized the mutation, expression, modification and function of the human ACE2 based on comprehensive bioinformatics analysis. Especially, the relationship between ACE2 expression and diseases, especially tumor was further discussed. ACE2 is highly conserved in different genera and families. We explored the correlation between ACE2 and disease based on the datasets of GCBI and GEO (Gene expression omnibus), and found the expression of ACE2 is related to heart failure. High prevalence of ACE2 mutations is observed in diffuse large B-cell lymphoma, uterine carcinosarcoma (UCS), and stomach adenocarcinoma (STAD). We first identified that highly expressed of ACE2 was linked to poor prognosis of overall survival for tumors of brain lower grade glioma (LGG). Specially, the expression level of ACE2 in kidney-related tumor tissues is much higher than that of normal kidney tissues. ACE2 is negatively correlated with the infiltration level of cancer-associated fibroblasts in most kinds of cancers, such as uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC); positively correlation in testicular germ cell tumors (TGCT). The different phosphorylation sites of ACE2 were analyzed in CPTAC dataset, and the DNA methylation of ACE2 in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), and rectum adenocarcinoma (READ) was lower than that of normal control by using SMART database. Moreover, we summarized the interaction proteins and targeted miRNAs of ACE2 through bioinformatics. Then we found the endocrine process and the regulation of systemic arterial blood pressure were involved in the functional mechanisms of ACE2 by using KEGG and GO analysis. Our study offers a relatively comprehensive understanding of ACE2.

Limited BA.5 neutralization by pre-exposure prophylaxis with tixagevimab/cilgavimab in CAR-T treated people (preprint)

CAR T-cell recipients experience profound B-cell aplasia and hypogammaglobulinemia, being unable to mount any humoral response and at higher risk for severe COVID-19. Tixagevimab/cilgavimab has been approved for COVID-19 pre-exposure prophylaxis (PrEP) in immunocompromised people. 150/150 mg of tixagevimab/cilgavimab does not adequately neutralize against Omicron BA.5 and these results support recommendations on dose increase to 300/300 mg for prophylaxis in order to enhance effectiveness probability, until the European regulatory agency makes a decision on the usability of this compound as the FDA has already done

Selecting initial therapy in CLL.

Targeted therapy is a powerful treatment option in chronic lymphocytic leukemia (CLL) that has outperformed conventional chemoimmunotherapy in most clinical settings. Except for selected young, fit patients with a mutated immunoglobulin heavy chain variable region gene, most patients benefit from targeted therapy with either a continuous BTK inhibitor or 1-year fixed-duration venetoclax-obinutuzumab as first-line treatment of CLL. Treatment selection is driven by patient-, treatment-, and disease-related factors, encompassing patient preference, concomitant medications, comorbidities, safety profile of the regimen, and TP53 aberration. Clinical trials are actively investigating the simultaneous inhibition of Bruton's tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) proteins with or without a CD20 monoclonal antibody, which can achieve deep response in most patients (52%-89% undetectable minimal residual disease in bone marrow).

Potent high-avidity neutralizing antibodies and T cell responses after COVID-19 vaccination in individuals with B cell lymphoma and multiple myeloma.

Individuals with hematologic malignancies are at increased risk for severe coronavirus disease 2019 (COVID-19), yet profound analyses of COVID-19 vaccine-induced immunity are scarce. Here we present an observational study with expanded methodological analysis of a longitudinal, primarily BNT162b2 mRNA-vaccinated cohort of 60 infection-naive individuals with B cell lymphomas and multiple myeloma. We show that many of these individuals, despite markedly lower anti-spike IgG titers, rapidly develop potent infection neutralization capacities against several severe acute respiratory syndrome coronavirus 2 variants of concern (VoCs). The observed increased neutralization capacity per anti-spike antibody unit was paralleled by an early step increase in antibody avidity between the second and third vaccination. All individuals with hematologic malignancies, including those depleted of B cells and individuals with multiple myeloma, exhibited a robust T cell response to peptides derived from the spike protein of VoCs Delta and Omicron (BA.1). Consistently, breakthrough infections were mainly of mild to moderate severity. We conclude that COVID-19 vaccination can induce broad antiviral immunity including ultrapotent neutralizing antibodies with high avidity in different hematologic malignancies.

Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals. (preprint)

How infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limited de novo response against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.

The response to BTN62b2 booster doses demonstrates that serum antibodies do not predict the establishment of immune B-cell memory in common variable immune deficiencies (preprint)

In patients with common variable immune deficiencies, primary vaccination followed by two booster doses is recommended for protection against COVID-19. Seroconversion has been shown in 60% of patients. We have no information on whether serum antibodies reflect the generation of durable immune memory. In a longitudinal study on 47 common variable immune deficiencies patients who received the third and fourth vaccine dose, we show that the measurement of specific antibodies is not sufficient to predict the establishment of immune memory and the ability to respond to antigen re-exposure. Our results indicate that the combination of antibodies and memory B cells responses represents a more reliable read-out of vaccine immune efficacy in vulnerable patients. This analysis may not only identify individuals remaining unprotected after vaccination and unable to respond to additional booster doses, but also address the search for the underlying immune defect and suggest patient-tailored management strategies.

[Warm autoimmune hemolytic anemia and IgM-monoclonal gammopathy following BNT162b2 COVID-19 vaccine in a patient with splenic marginal zone lymphoma].

There is currently no evidence that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine might be associated with the development of autoimmune hemolytic anemia or disease progression in patients with mature B-cell neoplasm. Our patient was a 71-year-old man with indolent mature B-cell neoplasm who had been monitored for many years without treatment. After receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine, he developed severe warm autoimmune hemolytic anemia. Although steroid therapy improved his anemia, he continued to develop IgM-monoclonal gammopathy, renal insufficiency, and splenomegaly. He was diagnosed with splenic marginal zone lymphoma after undergoing splenectomy. The splenectomy improved the patient's symptoms. We assessed his SARS-CoV-2 specific antibody response, but the patient's serologic response to the vaccine was impaired. In patients with mature B-cell neoplasm, a non-specific immune response after vaccination might be associated with paraneoplastic syndromes.