Waning Humoral Immune Response to SARS-CoV-2 Vaccination with Symptomatic Infection after Initiation of Anti-CD20 Treatment in a Patient with Multiple Sclerosis

Waning humoral responses to SARS-CoV-2 vaccination have been reported arguing for booster vaccinations even in healthy populations. Multiple sclerosis (MS) immunotherapy with anti-CD20 monoclonal antibodies may negatively influence morbidity and mortality of COVID-19. The opportunity to treat patients at risk for a severe COVID-19 course with specific monoclonal antibodies targeting SARS-CoV-2 represents an important novel measure for patient safety. We report a patient with waning humoral vaccination response around five months after two mRNA vaccination doses upon initiation of ocrelizumab treatment. Symptomatic COVID-19 infection was treated with casirivimab/imdevimab with rapid symptom recovery

The impact of immunotherapies on COVID-19 case fatality rates during the US vaccination campaign: a multidisciplinary open data analysis using FDA Adverse Event Reporting System and Our World in Data.

Introduction: Patients under immunotherapies were excluded from the pivotal trials of vaccinations against the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), and no population-level data on disease outcomes such as case fatality rates in relation to vaccination coverage exist. Our study aims to fill this gap by investigating whether CFRs in patients with immunotherapies decrease with increasing vaccination coverage in the total population. Methods: We combined aggregated open source data on COVID-19 vaccination coverage from "Our World in Data" with publicly available anonymized COVID-19 case reports from the FDA Adverse Event Reporting System to compute COVID-19 CFRs for patients under immunotherapy at different vaccination coverage levels in the total population. CFRs at different vaccination coverage levels were then compared to CFRs before vaccination campaign start. Results: While we found an overall decrease in CFRs on population level with increasing vaccination coverage, we found no decrease in people using anti-CD20 or glucocorticoids. Discussion: Risk-mitigation strategies on an individual- and population-level are thus still needed to lower the probability of fatal SARS-CoV2 infection for these vulnerable populations

COVID-19 in a Neuroimmunological Outpatient Cohort: The Bernese Experience

The COVID-19 pandemic specifically affects the management and treatment of patients with autoimmune neurological disorders. Major concerns include potentially higher risks of infection or severe disease course under certain immunotherapies used to treat those disorders and the influence of COVID-19 on the underlying disease. We present data of the neuroimmunological outpatient department of the University Hospital of Bern (Switzerland). 24 cases were analyzed, 19 of them suffered from Multiple Sclerosis. Of these 24 patients, 6 were hospitalized, 2/6 were treated in the Intensive Care Unit. Possible risk factors for severe course (defined as need for hospitalization) observed in our cohort included cardiovascular risk factors, treatment with B-cell depleting agents, Sphingosine-1 Phosphate Receptor Modulators, and oral steroid therapies. These data are based on a small, retrospective observational cohort and should be interpreted with caution, although they are in line with several other cohort studies

Multiple Sclerosis immunotherapies and COVID-19 mortality: an analysis of the FDA Adverse Event Reporting System.

Background Evidence on mortality risks associated with MS-immunotherapies during the SARS-CoV2 pandemic derived thus far mainly from single country experiences. Objective In this analysis, we aim to determine the frequency of COVID-19 associated fatality reports of patients receiving an MS-immunotherapy as reported to the international Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from February 2020 to March 2021. Methods In all, 1071 cases for this cross-sectional analysis were retrieved from FAERS and a multivariable logistic regression was performed. We adjusted for sex, age, region, month of report to FDA, immunotherapy-class and additionally for healthcare-system and pandemic-related metrics. Result Anti-CD20 therapies (60%) followed by sphingosine-1 phosphate modulators (12%) and dimethylfumarat (10%) were reported most frequently. In 50% of the cases, MS-phenotype is not reported, relapsing MS in 35% and progressive MS in 15%. Besides older age (odds ratio [OR]: 1.1; 95% confidence interval [CI]: 1.07-1.13; p < 0.01), anti-CD20 therapies were significantly associated with a higher risk of death (OR: 4.1; 95% CI: 1.17-14.46; p = 0.03), whereas female sex was associated with a reduced mortality risk (OR: 0.4, 95% CI: 0.22-0.72; p < 0.01). Conclusion Using international open access data and a multidisciplinary approach for risk prediction, we identified an increased mortality risk associated with anti-CD20 therapies, which is in line with national and multi-national cohort studies

Vaccine Hesitancy in Patients With Multiple Sclerosis: Preparing for the SARS-CoV-2 Vaccination Challenge.

OBJECTIVE Vaccine hesitancy is a complex public health issue referring to concerns about safety, efficacy, or need for vaccination. Using pneumococcal vaccination, which is recommend in anti-CD20-treated multiple sclerosis (MS) patients, as a model, we assessed vaccination behavior in patients with MS to prepare for the upcoming SARS-CoV-2 vaccination challenge. METHODS By a medical chart review, we retrospectively identified patients with MS treated with ocrelizumab at the University Hospital Bern in 2018-2020. Pneumococcal vaccination was discussed with the patients during clinical visits and highlighted in the after-visit summary addressed to the general practitioner before ocrelizumab initiation as part of our clinical standard of care. RESULTS Pneumococcal vaccination was performed in 71/121 (58.7%) of patients, and 50/121 (41.3%) patients were not vaccinated. Patients who did not get a pneumococcal vaccination were younger (no vaccination vs vaccination; mean [95% CI] 40.1 [36.1-44.1] vs 45.4 [41.9-48.8], p = 0.028) and had more frequently a relapsing remitting disease course (no vaccination vs vaccination, n [%]; 43/50 [86.0%] vs 49/71 [69.0%], p = 0.031). Furthermore, patients who did not get vaccination had more frequently a history of comorbid psychiatric disorder (no vaccination vs vaccination, n (%); 12/50 [24.0] vs 7/71 [9.8], p = 0.035). CONCLUSION Our study demonstrated that in our single-center cohort, 41.3% of patients with MS do not get the recommended pneumococcal vaccination. Future research should focus on vaccine hesitancy in the vulnerable cohort of patients with MS to improve the safety of MS immunotherapies

Application of the "risk of ambulatory disability" (RoAD) score in a "real-world" single-center multiple sclerosis cohort.

Survival analysis of reaching EDSS ≥4.0 based on RoAD score ≥4 (dashed line) and <4 (solid line) by Cox regression analysis. (A) Unadjusted regression analysis. (B) Regression controlled for sex and immunotherapy groups, and the trajectory of treatment changes during follow-up

Growing importance of brain morphometry analysis in the clinical routine: The hidden impact of MR sequence parameters.

Volumetric assessment based on structural MRI is increasingly recognized as an auxiliary tool to visual reading, also in examinations acquired in the clinical routine. However, MRI acquisition parameters can significantly influence these measures, which must be considered when interpreting the results on an individual patient level. This Technical Note shall demonstrate the problem. Using data from a dedicated experiment, we show the influence of two crucial sequence parameters on the GM/WM contrast and their impact on the measured volumes. A simulated contrast derived from acquisition parameters TI/TR may serve as surrogate and is highly correlated (r=0.96) with the measured contrast