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Journal of Neurology, Neurosurgery and Psychiatry ; 93(9):9, 2022.
Article in English | EMBASE | ID: covidwho-2297640


Anti-viral vaccination has rarely been associated with Guillain- Barre syndrome(GBS). We performed a population-based study of NHS England data and a UK multicentre surveillance study to investigate the relationship between COVID-19 vaccination and GBS. We linked GBS cases from England's National Immunoglobulin Database(NID) with COVID-19 vaccina- tion data from December 2020-July 2021. GBS temporally associated within a 6-week risk window of any COVID-19 vaccine was identified. We prospectively collected incident UK GBS cases January- November 2021 regardless of vaccine exposure. The NID recorded 996 English GBS cases January-October 2021. A spike of cases above the 2016-2020 average occurred March-April 2021. 198 cases occurred within 6 weeks of first-dose COVID-19 vaccina- tion (0.618cases/ 100,000vaccinations: 176 ChAdOx1 nCoV-19, 21 tozinameran, 1 mRNA-1273). First-dose ChAdOx1 nCoV-19 accounted for the excess of 98-140 GBS cases with a peak 24 days post-vaccination. First-dose tozinameran and seconddose any vaccination showed no excess GBS risk. The UK multicen- tre surveillance dataset (121 patients) identified no phenotypic or demographic differences between vaccinelinked and unlinked cases. First-dose ChAdOx1 nCoV-19 vaccination is associated with excess GBS risk 0.576 (95%CI 0.481-0.691) cases/100,000 doses. No specific features are associated with vaccinationrelated GBS cases. The mechanism of immunogenicity of ChAdOx1 nCoV-19- warrants further study.

HemaSphere ; 6:1930-1931, 2022.
Article in English | EMBASE | ID: covidwho-2032125


Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse;the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17;49%) had previously received therapy for LPL;median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26;54%) had <10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28;80%), leptomeningeal tissue biopsy (n=3;9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4;11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28;96%), MYD88L265P mutation (18/28;64%) and immunoglobulin gene rearrangement (12/28;43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) + thiotepa/idarubicin;n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1);one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had >4 cycles followed by BCNU/thiotepa autologous stem cell transplant;10 proceeded to 'consolidation' (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached;2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy;7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image: Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib;however, there are treatment-related toxicities emphasising the need for a tailored approach.

Clin Immunol ; 221: 108614, 2020 12.
Article in English | MEDLINE | ID: covidwho-912100


The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application as biomarkers of disease severity, respiratory failure and need of higher-level care. From analysis of 203 samples, CRP, IL-6, IL-10 and LDH were most strongly correlated with the WHO ordinal scale of illness severity, the fraction of inspired oxygen delivery, radiological evidence of ARDS and level of respiratory support (p ≤ 0.001). IL-6 levels of ≥3.27 pg/ml provide a sensitivity of 0.87 and specificity of 0.64 for a requirement of ventilation, and a CRP of ≥37 mg/l of 0.91 and 0.66. Reliable stratification of high-risk cases has significant implications on patient triage, resource management and potentially the initiation of novel therapies in severe patients.

C-Reactive Protein/metabolism , COVID-19/diagnosis , Cytokine Release Syndrome/diagnosis , Interleukin-6/blood , Respiratory Distress Syndrome/diagnosis , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/therapy , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/therapy , Cytokine Release Syndrome/virology , Female , Hospitalization , Humans , Interleukin-10/blood , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Respiration, Artificial , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Risk Factors , Severity of Illness Index