CIDP: Analysis of Immunomarkers During COVID-19 mRNA-Vaccination and IVIg-Immunomodulation: An Exploratory Study.

Availability of COVID-19 mRNA vaccine for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous immunoglobulin (IVIg) raises the question of whether COVID-19 mRNA vaccine influences disease activity or IVIg-mediated immunomodulation in CIDP. In this exploratory study, blood samples of CIDP patients on IVIg treatment were longitudinally analyzed before and after vaccination with a COVID-19 mRNA vaccine. A total of 44 samples of eleven patients were characterized at four timepoints by ELISA and flow cytometry in terms of immunomarkers for disease activity and IVIg-immunomodulation. Apart from a significantly lower expression of CD32b on naïve B cells after vaccination, no significant alteration of immunomarkers for CIDP or IVIg-mediated immunomodulation was observed. Our exploratory study suggests that COVID-19 mRNA vaccine does not have a relevant impact on immune activity in CIDP. In addition, immunomodulatory effects of IVIg in CIDP are not altered by COVID-19 mRNA vaccine. This study was registered in the German clinical trial register (DRKS00025759). Overview over the study design. Blood samples of CIDP patients on recurrent IVIg treatment and vaccination with a COVID-19 mRNA vaccine were obtained at four timepoints for cytokine ELISA and flow cytometry, to assess key cytokines and cellular immunomarkers for disease activity and IVIg-immunomodulation in CIDP.

Risk and course of COVID-19 in immunosuppressed patients with myasthenia gravis.

BACKGROUND: Patients with myasthenia gravis (MG) are potentially prone for a severe COVID-19 course, but there are limited real-world data available on the risk associated with COVID-19 for patients with MG. Here, we investigate whether current immunosuppressive therapy (IST) influences the risk of SARS-CoV-2 infection and COVID-19 severity. METHODS: Data from the German myasthenia gravis registry were analyzed from May 2020 until June 2021 and included patient demographics, MG disease duration, comorbidities, current IST use, COVID-19 characteristics, and outcomes. Propensity score matching was employed to match MG patients with IST to those without, and multivariable binary logistic regression models were used to determine associations between IST with (1) symptomatic SARS-CoV-2 infection and (2) severe COVID-19 course, as measured by hospitalization or death. RESULTS: Of 1379 patients with MG, 95 (7%) patients (mean age 58 (standard deviation [SD] 18) presented with COVID-19, of which 76 (80%) received IST at time of infection. 32 patients (34%) were hospitalized due to COVID-19; a total of 11 patients (12%) died. IST was a risk factor for hospitalization or death in the group of COVID-19-affected MG patients (odds ratio [OR] 3.04, 95% confidence interval [CI] = 1.02-9.06, p = 0.046), but current IST was not associated with a higher risk for SARS-CoV-2 infection itself. DISCUSSION: In this national MG cohort study, current IST use was a risk factor for a severe disease course of COVID-19 but not for SARS-CoV-2 infection itself. These data support the consequent implementation of effective strategies to prevent COVID-19 in this high-risk group. TRIAL REGISTRATION INFORMATION: German clinical trial registry ( https://www.drks.de ), DRKS00024099, first patient enrolled: February 4th, 2019.

Meaningful use of imaging resources to rule out cerebral venous sinus thrombosis after ChAdOx1 COVID-19 vaccination: Evaluation of the AHA diagnostic algorithm with a clinical cohort and a systematic data review.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) with cerebral venous thrombosis (CVST) is an improbable (0.0005%), however potentially lethal complication after ChAdOx1 vaccination. On the other hand, headache is among the most frequent side effects of ChAdOx1 (29.3%). In September 2021, the American Heart Association (AHA) suggested a diagnostic workflow to facilitate risk-adapted use of imaging resources for patients with neurological symptoms after ChAdOx1. We aimed to evaluate the AHA workflow in a retrospective patient cohort presenting at four primary care hospitals in Germany for neurological complaints after ChAdOx1. Scientific literature was screened for case reports of VITT with CVST after ChAdOx1, published until September 1st, 2021. One-hundred-thirteen consecutive patients (77 female, mean age 38.7 +/- 11.9 years) were evaluated at our institutes, including one case of VITT with CVST. Further 228 case reports of VITT with CVST are published in recent literature, which share thrombocytopenia (225/227 reported) and elevated d-dimer levels (100/101 reported). The AHA workflow would have recognized all VITT cases with CVST (100% sensitivity), the number needed to diagnose (NND) was 1:113. Initial evaluation of thrombocytopenia or elevated d-dimer levels would have lowered the NND to 1:68, without cost of sensitivity. Hence, we suggest that in case of normal thrombocyte and d-dimer levels, the access to further diagnostics should be limited by the established clinical considerations regardless of vaccination history.

Ocrelizumab Extended Interval Dosing in Multiple Sclerosis in Times of COVID-19.

OBJECTIVE: To evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020). RESULTS: Three hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09-13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695-2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19+ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19+ B-cell repopulation. CONCLUSION: Our data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.