Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group.

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.

Immunological response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis treated with Rituximab.

In this study we employed a comprehensive immune profiling approach to determine innate and adaptive immune response to SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis receiving rituximab. By multicolour cytometry, dendritic and natural killer cells, B- and T-cell subsets, including T-cells producing IFN-γ stimulated with SARS-CoV-2 peptides, were analysed after infection and mRNA vaccination. In the same conditions, anti-spike antibodies and cytokines' levels were measured in sera. Despite the impaired B cell and humoral response, rituximab patients showed an intact innate, CD8 T-cell and IFN-γ specific CD4+ and CD8+ T-cell response after infection and vaccination, comparable to controls. No signs of cytokine mediated inflammatory cascade was observed. Our study provides evidence of protective immune response after SARS-CoV-2 infection and mRNA vaccines in patients with myasthenia gravis on B cell depleting therapy and highlights the need for prospective studies with larger cohorts to clarify the role of B cells in SARS-CoV-2 immune response.

Analysis of Rituximab Use, Time Between Rituximab and SARS-CoV-2 Vaccination, and COVID-19 Hospitalization or Death in Patients With Multiple Sclerosis.

Importance: Rituximab and other B-cell-depleting therapies blunt humoral responses to SARS-CoV-2 vaccines, particularly when the vaccine is administered within 6 months of an infusion. Whether this translates into an increased risk of hospitalization or death from COVID-19 is unclear. Objectives: To examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2-vaccinated persons with multiple sclerosis (MS) and whether delaying vaccination more than 6 months after rituximab treatment is associated with decreased risk. Design, Setting, and Participants: This retrospective cohort study used Kaiser Permanente Southern California's electronic health record to identify individuals from January 1, 2020, to February 15, 2022, who had MS and who had been vaccinated against SARS-CoV-2. Exposures: Rituximab treatment compared with disease-modifying therapies (DMTs) that do not interfere with vaccine efficacy or being untreated (no or other DMT group). Among rituximab-treated patients, the exposure was receiving at least 1 vaccine dose more than 6 months after their last infusion compared with receiving all vaccine doses 6 months or less since their last infusion. Main Outcomes and Measures: The main outcome was hospitalization due to COVID-19 infection. The odds of infection resulting in hospitalization following SARS-CoV-2 vaccination were adjusted for race and ethnicity, advanced MS-related disability; vaccine type; booster dose; and, among rituximab-treated only analyses, cumulative rituximab dose and dose at last infusion. Exposures, outcomes, and covariates were collected from the electronic health record. Results: Among 3974 SARS-CoV-2-vaccinated people with MS (mean [SD] age, 55.3 [15] years; 2982 [75.0%] female; 103 [2.6%] Asian or Pacific Islander; 634 [16.0%] Black; 953 [24.0%] Hispanic; 2269 [57.1%] White; and 15 [0.3%] other race or ethnicity), rituximab-treated patients (n = 1516) were more likely to be hospitalized (n = 27) but not die (n = 0) compared with the 2458 individuals with MS receiving no or other DMTs (n = 7 and n = 0, respectively; adjusted odds ratio [aOR] for hospitalization, 7.33; 95% CI, 3.05-17.63). Receiving messenger RNA (mRNA) SARS-CoV-2 vaccine (aOR, 0.36; 95% CI, 0.15-0.90; P = .03) and receiving a booster vaccination (aOR, 0.31; 95% CI, 0.15-0.64; P = .002) were independently associated with a decreased risk of hospitalization for COVID-19. Among vaccinated rituximab-treated individuals with MS, receiving any vaccination dose more than 6 months after the last rituximab infusion was associated with a reduced risk of COVID-19 hospitalization (aOR, 0.22; 95% CI, 0.10-0.49). Conclusions and Relevance: This cohort study's findings suggest that rituximab-treated people with MS should be strongly encouraged to receive mRNA SARS-CoV-2 vaccines and boosters more than 6 months after their last rituximab infusion whenever possible. The low absolute risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS should not preclude use of rituximab, which has marked efficacy, cost, and convenience advantages over other DMTs.

Improvement of humoral immunity by repeated dose-intensified COVID-19 vaccinations in primary non- to low-responders and B cell deficient rheumatic disease patients.

OBJECTIVE: To determine whether repeated, dose-intensified mRNA vaccinations against COVID-19 increase humoral immunity in previously low-responding patients with autoimmune rheumatic diseases (AIRD), including rituximab-treated and B cell depleted patients. METHODS: Of 308 AIRD patients receiving basic immunization, 98 had a low serological response against SARS-CoV-2 with a neutralizing capacity of < 70% using surrogate neutralization assay. 38 patients received a third vaccination with 30 µg BNT162b2 16 weeks after second vaccination. If neutralizing serum capacity was below 70% four weeks after the last vaccination, then the fourth vaccination (n = 19) and the fifth (n = 4) vaccination with 100 µg mRNA-1273 took place eight weeks after the last vaccination. RESULTS: Each of the three booster vaccinations resulted in a significant increase of mean serum neutralizing capacity (3rd: Δ = 42%, p < 0.001; 4th: Δ = 19%, p = 0.049 and 5th: Δ = 51%, p = 0.043) and produced a significant proportion of high-responders (3rd: 34%; 4th: 32% and 5th: 75%). Low B cell counts (p = 0.047), lower previous antibody response (p < 0.001) and rituximab therapy (p = 0.021) were negatively associated with successful response to the third but not to the fourth vaccination. Remarkably, substantial increases in neutralization capacity of up to 99% were observed after repeated vaccinations in B cell depleted patients. CONCLUSION: AIRD patients with low humoral response benefited from up to three repeated dose-intensified mRNA booster vaccinations - despite low B cell count and previous rituximab therapy. Each additional vaccination substantially reduced the number of low-responding, vulnerable patients.

B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab.

OBJECTIVE: To assess factors associated with serologic response to the coronavirus 2019 (COVID-19) booster vaccine in patients with autoimmune rheumatic diseases treated with rituximab (RTX) who were previously serologically unresponsive to the initial vaccine series. METHODS: A retrospective chart review of patients treated with RTX who failed to demonstrate a serologic response to the first SARS-CoV-2 vaccination series and subsequently received an mRNA vaccine booster was performed. Serologic response ≥ 4 weeks after the booster was the primary outcome. Fisher exact tests, t tests, and Wilcoxon rank-sum tests were used for comparisons. RESULTS: In 31 patients who were previously seronegative, 68% seroconverted following a booster of the COVID-19 vaccine. B cell reconstitution was significantly different between those with positive (median 1.79, IQR 0.65-3.00) and negative (median 0, IQR 0-0) serologic responses to the booster. The days from last RTX dose were also statistically different among seroconverters (median 301, IQR 251-368) vs nonseroconverters (median 188, IQR 169-245). Demographic characteristics were not associated with serologic positivity. Positive predictive value of B cell presence was 90.9% (95% CI 70.8-98.9) and negative predictive value was 100% (95% CI 59-100) for serologic response to the mRNA booster vaccine. Positive predictive value of time ≥ 6 months from last RTX dose to booster was 78.3% (95% CI 56.3-92.5) and the negative predictive value was 62.5% (95% CI 24.5-91.5). CONCLUSION: Detectable B cells and longer time from last RTX exposure were associated with the development of anti-SARS-CoV-2 spike protein antibodies following the booster vaccine. These findings should be considered in timing boosters in patients treated with RTX.

Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective, nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C).

OBJECTIVE: To assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA). METHODS: We used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments. RESULTS: A total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52-72) years, 76% of the cohort was female, 68% was non-Hispanic/Latinx White, and 73% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio [aOR] 2.1, 95% confidence interval 1.5-3.0), ICU admission (aOR 5.2, 1.8-15.4) and invasive ventilation (aOR 2.7, 1.4-5.5). Results were confirmed in multiple sensitivity analyses. CONCLUSION: Our findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.

Peripheral Ulcerative Keratitis in a Young Lady with Systemic Lupus Erythematosus Post Rituximab Infusion-A Case Report.

AIM: We report a new ocular finding of episcleritis (OD) and peripheral ulcerative keratitis (OS) in a 40-year-old lady with a 13-year history of systemic lupus erythematosus (SLE), 3 weeks post-rituximab infusion. MATERIALS & METHODS: Retrospective case report. RESULTS: A 40-year-old lady with a history of SLE and 3 weeks post rituximab infusion developed a new onset episcleritis (OD) and peripheral ulcerative keratitis (OS). As the PUK continued to advance with a leading edge, intravenous methyl prednisolone 1 gm/day was given for 3 days followed by a slow tapering course of oral prednisolone 50 mg/day. Though her ocular inflammation resolved, she developed pneumonia 6 weeks later. At 10 months follow-up, there were no ocular recurrences. She is currently on mycophenolate mofetil 2 gm/day along with oral prednisolone of 10 mg/day. CONCLUSION: This case highlights the new occurrence of episcleritis and PUK in SLE post-rituximab infusion.

Immunogenicity and Safety of SARS-CoV-2 Vaccination in Patients With Rheumatic Diseases: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis examining the immunogenicity and safety of SARS-CoV-2 vaccination in patients with RD. METHODS: We systematically searched PubMed/MEDLINE and Scopus to identify observational studies that examined the immunogenicity and safety of SARS-CoV-2 vaccination in RD patients. Information on disease, immunosuppressant, vaccine type, and proportion of patients with serologic response was obtained from each study. RESULTS: There were 25 eligible studies. The pooled rate of seroconversion was 0.79 (95% confidence interval [CI], 0.72-0.86). Compared with control subjects, the odds of seroconversion were significantly lower (odds ratio, 0.11; 95% CI, 0.05-0.24). Users of rituximab showed the lowest rate of seroconversion (0.39; 95% CI, 0.29-0.51) followed by mycophenolate (0.56; 95% CI, 0.40-71). On the other hand, users of interleukin 17 (0.94; 95% CI, 0.78-0.98) and tumor necrosis factor inhibitors (0.94; 95% CI, 0.84-0.98) showed high seroconversion rate. Regarding safety of COVID-19 vaccine, approximately 2% of patients reported severe adverse events and 7% reported diseases flares following the first or second dose. CONCLUSION: Vaccination against SARS-CoV-2 appears to be safe. Most RD patients developed humoral immune response following vaccination. However, the odds of seroconversion were significantly lower in RD patients compared with controls. This is likely driven by certain immunosuppressants including rituximab and mycophenolate. Future studies need to identify strategies to improve vaccine response in these patients.

Regen-COV-2 Antibody Cocktail Mediated Clearance of SARS-COV-2 in an Immunocompromised Patient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) affects different people in different ways. Most infected people develop mild to moderate illness and recover without hospitalization. This case report presents a patient who had difficulty eradicating the corona virus due to being treated with rituximab, which depletes B lymphocytes and therefore disables the production of neutralizing antibodies. The regen-COV-2 antibody cocktail consists of two monoclonal antibodies, casirivimab and imdevimab. This cocktail successfully helped the patient's immune system eradicate the virus without auto specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production. In vitro studies confirm that eradication of the intact the virus. This case report emphases the importance of providing external antiviral antibodies regularly, like the regen-COV-2 antibody cocktail, as post- and even pre- SARS-CoV-2 infection prophylaxis in patients treated with rituximab.

Seroconversion among rituximab-treated patients following SARS-CoV-2 vaccine supplemental dose.

Rituximab (RTX) is a very effective treatment for autoimmune rheumatic diseases (AIRD), but it increases infection risk and impairs vaccine responses. Herein we evaluated the antibody response of RTX-treated patients to the supplemental COVID-19 vaccine. After the supplemental dose, 53.1% of patients had detectable antibody titers. Only 36% of patients who did not mount an antibody response after the original vaccine series did have detectable antibodies after the supplemental dose (seroconversion). Patients with undetectable CD20+ cell levels did not seroconvert while hypogammaglobulinemia was associated with a 15-times decrease in the likelihood of seroconversion. Although we noted 11 COVID-19 infections after the supplemental dose, no patients who received monoclonal antibodies pre-exposure prophylaxis had COVID-19 afterwards. We propose that patients receiving RTX should continue to be prioritized for prophylaxis measures and that vaccination should be timed after B cell recovery wherever possible.

Severe Pancytopenia After COVID-19 Revealing a Case of Primary Bone Marrow Diffuse Large B Cell Lymphoma.

BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). While bone marrow (BM) involvement is common in lymphoma, primary bone marrow (PBM) DLBCL is extremely rare. We present a case of PBM DLBCL discovered in a patient with COVID-19. CASE REPORT An 80-year-old man presented with generalized abdominal pain, weight loss, fever, fatigue, anorexia, and watery diarrhea over a 3-month period. Physical examination was unremarkable. Laboratory workup revealed anemia, thrombocytopenia, and elevated inflammation markers. SARS-COV-2 PCR was positive, while blood cultures were negative. A rapid decline in the white blood cell count in the following days prompted a BM biopsy, confirming the diagnosis of PBM DLBCL. Computed tomography (CT) did not show thoracic or abdominal lymphadenopathy. The patient received packed red blood cell and platelet transfusions, granulocyte colony-stimulating factor (G-CSF) for pancytopenia, and empirical antibiotics for suspected infection. Due to active COVID-19 and advanced age, cytotoxic chemotherapy was delayed. Rituximab and prednisone were initiated on day 9, followed by an infusion reaction, which led to treatment discontinuation. He died 2 days later. CONCLUSIONS Diagnosing PBM malignancy is challenging, especially with coexisting infection. It is essential to suspect underlying BM malignancy in patients with clinical deterioration and worsening pancytopenia despite adequate treatment. The diagnosis of PBM DLBCL requires the absence of lymphadenopathy, and the presence of histologically confirmed DLBCL. Prompt management with combination chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with/without hematopoietic stem cell transplant can improve the prognosis.

Timing of SARS-CoV-2 Vaccination Matters in People With Multiple Sclerosis on Pulsed Anti-CD20 Treatment.

BACKGROUND AND OBJECTIVES: Our objective was to investigate cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in a cohort of people with multiple sclerosis (pwMS) on pulsed B-cell-depleting treatment (BCDT). In particular, we intended to evaluate a possible association between immune responses and the timing of vaccination under BCDT. METHODS: We conducted a cross-sectional study among pwMS on pulsed BCDT or without disease-modifying treatment after completed SARS-CoV-2 vaccination. Samples were collected during routine clinical visits at the Multiple Sclerosis Center Dresden, Germany, between June 2021 and September 2021. Blood was analyzed for SARS-CoV-2 spike protein-specific antibodies and interferon-γ release of CD4 and CD8 T cells on stimulation with spike protein peptide pools. Lymphocyte subpopulations and total immunoglobulin levels in the blood were measured as part of clinical routine. RESULTS: We included 160 pwMS in our analysis, comprising 133 pwMS on BCDT (n = 132 on ocrelizumab and n = 1 on rituximab) and 27 without disease-modifying treatment. Humoral and cellular anti-SARS-CoV-2 responses were reciprocally regulated by the time between the last BCDT cycle and vaccination. Although antibody responses increased with prolonged intervals between the last BCDT cycle and vaccination, CD4 and CD8 T-cell responses were higher in pwMS vaccinated at early time points after the last BCDT cycle compared with untreated pwMS. T-cellular vaccination responses correlated with total, CD3 CD4, and partly with CD3 CD8 lymphocyte counts. Humoral responses correlated with CD19 lymphocyte counts. Status post coronavirus disease 2019 infection led to significantly increased SARS-CoV-2-specific T-cell and antibody responses. DISCUSSION: Delaying BCDT is currently discussed as a strategy to optimize humoral responses to SARS-CoV-2 vaccination. However, T cells represent an important line of defense against SARS-CoV-2 infection as well, especially in light of emerging variants of concern. We observed enhanced CD4 and CD8 T-cellular responses in pwMS receiving vaccination at early time points after their last BCDT cycle. These data may influence clinical decision making with respect to vaccination strategies in patients receiving BCDT.

[Immuno-inflammatory rheumatic diseases and COVID-19: analysis of clinical outcomes according to the data of the register of patients of the Novosibirsk region receiving therapy with genetically engineered biological drugs].

BACKGROUND: Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic. AIM: To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs. MATERIALS AND METHODS: A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020. RESULTS: According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%. CONCLUSION: Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

Immunogenicity of inactivated COVID-19 vaccine in patients with autoimmune inflammatory rheumatic diseases.

Progress has been made in COVID-19 vaccine development, with encouraging safety and efficacy data. The purpose of this study was to investigate the immunogenicity of inactivated COVID-19 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Patients with AIIRD (n = 101) were included in this study. All patients received 2 doses of inactivated COVID-19 vaccine. Serum anti-S1/RBD protein IgG was detected 2-16 weeks after the second vaccination. Seropositivity was defined as IgG ≥ 1.00 bound antibody unit S/CO. Immunogenicity of inactivated COVID-19 vaccine was assessed by seropositivity rate and the levels of serum IgG antibody against anti-S1/RBD protein, compared with the general population (n = 46). There was no difference by statistical significance in the seropositivity rate between patients with AIIRD (82.2%) and SLE (86.1%) and the control group (93.5%), p > 0.05. The level of anti-S1/RBD protein IgG antibodies in patients with AIIRD (median [IQR], 8.8 [2.2-17.3]) and SLE (median [IQR], 9.6 [2.4-20.4]) was comparable to that in the control group (median [IQR], 7.2 [3.1-14.2]), p > 0.05. Patients treated with glucocorticoids(GCs) (median dose, [IQR]: 2.5 mg/day [IQR 2.5-5.0]) or hydroxychloroquine(HCQ) or GCs + HCQ without other immunomodulatory medications, had an appropriate immunogenic response(88.1%) with high levels of anti-S1/RBD protein IgG(median [IQR], 12.1 [6.5-20.4]). Neither of patients treated with rituximab had positive serum antibodies, which was statistically significant, compared with the control group (p < 0.01). Compared with the control group, methotrexate(MTX) and iguratimod(IGU) was significantly reduced the level of anti-S1/RBD protein IgG antibodies. Inactivated COVID-19 vaccine had appropriate immunogenicity in patients with AIIRD. Immunogenicity of inactivated COVID-19 vaccine was severely impaired by rituximab, and also suppressed by MTX and IGU, while low doses of GC and HCQ had negligible effect.

Strongyloidiasis - diagnostic and therapeutic dilemmas in hyperinfection patients: a case series.

The helminth infection caused by Strongyloides stercoralis is widespread in tropical regions, but rare in European countries. Unfamiliarity with the disease and diagnostic obstacles could contribute to its lethal outcome. Frequent use of corticosteroids during the COVID-19 pandemic could increase its significance. The aim of this retrospective descriptive study was to explore disease patterns and discuss clinical dilemmas in patients with S. stercoralis hyperinfection treated at the University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic' in Zagreb, Croatia, between 2010 and 2021. Five out of 22 (22.7%) immunosuppressed patients treated due to strongyloidiasis developed hyperinfection. All patients were male, median 64 years; four were immunosuppressed by corticosteroids (although ileum resection could have been the trigger in one) and one by rituximab. The diagnosis was established after a median of 1.5 months of symptom duration, accidentally in all patients, by visualizing the parasite in the gastric/duodenal mucosa in four cases, and bronchial aspirate in one. All patients were cachectic, four out of five had severe hypoalbuminemia and all suffered secondary bacterial/fungal infection. Despite combined antibiotic, antifungal and antihelmintic therapy, three out of five of the patients died, after failing to clear living parasites from stool samples. We can conclude that significant delays in diagnosis and lack of clinical suspicion were observed among our patients with the most severe clinical presentations of strongyloidiasis. Although being beyond diagnostic recommendations for strongyloidiasis, an early upper gastrointestinal endoscopy with mucosal sample analysis could expedite diagnosis in severe, immunosuppressed patients. The persistence of viable parasites in the stool despite antihelmintic therapy should be further investigated.

New-Onset and Relapsed Membranous Nephropathy post SARS-CoV-2 and COVID-19 Vaccination.

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and COVID-19 vaccination, new-onset and relapsed clinical cases of membranous nephropathy (MN) have been reported. However, their clinical characteristics and pathogenesis remained unclear. In this article, we collected five cases of MN associated with SARS-CoV-2 infection and 37 related to COVID-19 vaccination. Of these five cases, four (4/5, 80%) had acute kidney injury (AKI) at disease onset. Phospholipase A2 receptor (PLA2R) in kidney tissue was negative in three (3/5, 60%) patients, and no deposition of virus particles was measured among all patients. Conventional immunosuppressive drugs could induce disease remission. The underlying pathogenesis included the subepithelial deposition of viral antigens and aberrant immune response. New-onset and relapsed MN after COVID-19 vaccination generally occurred within two weeks after the second dose of vaccine. Almost 27% of patients (10/37) suffered from AKI. In total, 11 of 14 cases showed positive for PLA2R, and 20 of 26 (76.9%) presented with an elevated serum phospholipase A2 receptor antibody (PLA2R-Ab), in which 8 cases exceeded 50 RU/mL. Conventional immunosuppressive medications combined with rituximab were found more beneficial to disease remission for relapsed patients. In contrast, new-onset patients responded to conservative treatment. Overall, most patients (24/37, 64.9%) had a favorable prognosis. Cross immunity and enhanced immune response might contribute to explaining the mechanisms of MN post COVID-19 vaccination.

Risk and severity of SARS-CoV-2 reinfection among patients with multiple sclerosis vs. the general population: a population-based study.

BACKGROUND: We conducted this study to compare the risk of reinfection between multiple sclerosis (MS) patients and a control group without MS. METHOD: In this retrospective study, data of all SARS-CoV-2 tests (n = 793,301) and almost all MS patients (n = 10,639) in Isfahan province were collected from January 01, 2020 to August 22, 2021. Of the 2196 MS patients and 793,301 persons from the general population who had been tested at least once, 3 control for each MS patient were identified, leaving 1560 MS patients and 4680 controls without MS. We compared the risk of reinfection after 90 days of a primary infection between those with and without a previous positive COVID-19 test. RESULTS: 736 (47.2%) MS patients and 2013 (43.0%) control individuals had at least one positive test. A total of 17 (2.3%) and 22 (1.1%) possible reinfections in MS and control groups were observed. The estimated protection against reinfection in all MS patients, MS patients on rituximab, MS patients on DMTs rather than rituximab, and controls were 68.2% (46.2, 81.2%), 57.4% (- 0.1, 83.1%), 71.5% (45.5, 85.2%), and 82.1% (72.1, 88.5%), respectively. We found no statistically significant difference in estimated protection (p = 0.123) and odd of reinfection (adjusted OR: 2.01 [0.98, 4.08]) between all MS patients and control group. Two patients were hospitalized at first infection but none required hospitalization at reinfection event. CONCLUSIONS: MS patients on rituximab may be at a greater risk of reinfection. Further studies are required to assess the risk of the second reinfection among the MS population.