Symptomatic COVID-19 course and outcomes after three mRNA vaccine doses in multiple sclerosis patients treated with high-efficacy DMTs.

BACKGROUND: Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax. OBJECTIVES: The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ). METHODS: Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use. RESULTS: Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed. CONCLUSION: Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.

Previously independent patients with mild-symptomatic COVID-19 are at high risk of developing cognitive impairment but not depression or anxiety.

OBJECTIVES: The aim of the study was to explore the cognitive functions of a large sample of hospitalised subjects with mild symptomatic Coronavirus Disease (COVID-19) who were previously independent at home and without neurological diseases. METHODS: Patients admitted in a COVID-19 Unit for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection between November 2020 and March 2021 were recruited. Inclusion criteria were: being independent at home before the infection, radiologically confirmed COVID-19 pneumonia, positive reverse transcriptase-polymerase chain reaction nasopharyngeal swab and no oxygen supplementation at the time of evaluation. EXCLUSION CRITERIA: cognitive impairment or neurological diseases previous to the infection, delirium episodes, and history of any mechanical ventilation use. They were evaluated with Montreal Cognitive Assessment (MoCA), Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Out of 522 subjects admitted in the COVID-19 Unit, 90 were enrolled [mean age = 68.32(11.99); 46M/44F]. An impaired MoCA (cut-off < 23) was found in 60 subjects (66.66 %). Pathological scores were obtained by 36.7 % of the subjects with <65 years and 78.3 % of those older than 65 years. A high prevalence of executive function and memory impairment was detected. CONCLUSIONS: The results underline a high rate of cognitive impairment in previously independent mild COVID-19 patients. This might represent a potential threat for the everyday independence of these patients due to the consequences on everyday life activities and work following discharge from hospital. These subjects should, therefore, be monitored in order to allow a better understanding of the progression and consequences of the so-called "Long COVID".

Benign COVID-19 in an Aggressive Case of Aquaporin-4 Neuromyelitis Optica Treated with Tocilizumab

Aggressive neuromyelitis optica spectrum disorders (NMOSDs) with antibodies (Abs) against aquaporin-4 (AQP4) can be treated by blocking the interleukin 6 (IL6) pathways with tocilizumab. This IL6-inhibitor was employed to treat coronavirus disease 2019 (COVID-19) pneumonia with unconclusive results. We present a 52-year-old woman with AQP4 NMOSD, unresponsive to rituximab, that stabilized on tocilizumab one year after the disease onset. She was bed-bound and progressively recovered her mobility. During intensive rehabilitation, she presented fever and cough for one week with nasopharyngeal swabs positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This mild COVID-19 recovered spontaneously without sequelae, and the monthly tocilizumab infusions were continued for another 10 months. Subsequently, serious and prolonged respiratory and urinary infections caused treatment interruption, and then her disease re-activated. In our case, tocilizumab was effective in preventing NMOSD relapse and was safe to use during SARS-CoV-2 infection.

Guillain-Barré Syndrome Related and Unrelated to COVID-19: Clinical Follow-Up in the COVID-19 Era.

OBJECTIVE: COVID-19 has been associated with neurological complications such as Guillain-Barre syndrome (GBS). Several cases have been reported but without functional outcome data after intensive rehabilitation and medium-term follow-up. METHODS: In this observational study, patients were admitted in 2019 and 2020 to inpatient rehabilitation for GBS and were examined using the Barthel index, GBS-Disability Scale, and Medical Research Scale-sum score at admission, discharge, and at least 6 months after onset of symptoms. All the participants received personalized, goal-oriented inpatient rehabilitative treatment for the recovery of self-sufficiency in everyday life. RESULTS: Eleven people with GBS-3 cases related to COVID-19-were admitted in 2019 and 2020 to inpatient rehabilitation. Eight patients with GBS not related to COVID-19 experienced a high complication rate during inpatient rehabilitation, with 2 deaths due to sepsis. In this cohort, a higher prevalence than expected of acute motor axonal neuropathy was also detected. The COVID-19-related GBS group did not have any complications. After a mean of 10.11 months (SD = 4.46 months), 55.55% of patients regained autonomous walking. CONCLUSION: COVID-19-related GBS appeared to have a better clinical outcome than GBS that was not COVID-19 related. A higher than usual prevalence of acute motor axonal neuropathy form was encountered. More follow-up studies are needed to understand whether the recovery of GBS related to COVID-19 might be different from that of GBS unrelated to COVID-19. IMPACT: No data are currently available on the follow-up of GBS in the COVID-19 era and on the functional outcome of those patients. This study provides important information indicating that GBS related to COVID-19 might have a better clinical outcome than GBS unrelated to COVID-19.

Study protocol on advance care planning in multiple sclerosis (ConCure-SM): intervention construction and multicentre feasibility trial.

INTRODUCTION: Multiple sclerosis (MS) is the most common cause of progressive neurological disability in young adults. The use of advance care planning (ACP) for people with progressive MS (pwPMS) remains limited. The ConCure-SM project aims to assess the effectiveness of a structured ACP intervention for pwPMS. The intervention consists of a training programme on ACP for healthcare professionals caring for pwPMS, and a booklet to be used during the ACP conversation. Herein, we describe the first two project phases. METHODS: In phase 1 we translated and adapted, to the Italian legislation and MS context, the ACP booklet of the National ACP Programme for New Zealand. Acceptability, comprehensibility and usefulness of the booklet were assessed via 13 personal cognitive interviews with pwPMS and significant others (SOs), and one health professional focus group. Based on these findings, we will revise the booklet. In phase 2 we will conduct a single-arm pilot/feasibility trial with nested qualitative study. Participants will be 40 pwPMS, their SOs, health professionals from six MS and rehabilitation centres in Italy. In the 6 months following the ACP conversation, we will assess completion of an advance care plan document (primary outcome), as well as safety of the intervention. Secondary outcomes will be a range of measures to capture the full process of ACP; patient-carer congruence in treatment preferences; quality of patient-clinician communication and caregiver burden. A qualitative process evaluation will help understand the factors likely to influence future implementation and scalability of the intervention. ETHICS AND DISSEMINATION: The project is coleaded by a neurologist and a bioethicist. Phase 1 has received ethical approvals from each participating centre, while phase 2 will be submitted to the centres in May 2021. Findings from both phases will be disseminated widely through peer-reviewed publications, conferences and workshops. TRIAL REGISTRATION NUMBER: ISRCTN48527663; Pre-results.

Benign SARS-CoV-2 infection in MOG-antibodies associated disorder during tocilizumab treatment.

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) represents a demyelinating disorder for which tocilizumab, an anti-IL6 receptor, has been tested to prevent disabling relapses. In a subgroup of patients affected with novel Coronavirus disease (COVID-19), tocilizumab has also increased the survival rate. We present the case of a 31-years-old Caucasian patient who experienced an almost asymptomatic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection during treatment with tocilizumab, which was continued due to the very high risk of relapses of the patient. According to this case, tocilizumab might be not discontinued during COVID-19.