The Impact of SARS-CoV-2 Infection in Unvaccinated Multiple Sclerosis Patients on Disease-Modifying Therapies.

OBJECTIVE: Disease-modifying therapies (DMTs) in multiple sclerosis (MS) may affect the course and outcome of COVID-19, but withholding them could permit disease activity. This study aimed to understand the course of COVID-19 in unvaccinated patients with MS on disease-modifying therapies. SUBJECTS AND METHODS: This descriptive study examined the course of COVID-19 among infected patients with MS followed up at a large tertiary center in Kuwait between March 1, 2020, and March 1, 2021. All subjects were outpatients at the time of data collection. RESULTS: We studied 51 patients with MS confirmed to be infected with SARS-CoV-2 using real-time polymerase chain reaction. Of these patients, 33/51 were female, median age was 35 years (IQR 27-39 years), median Expanded Disability Status Scale score was 1.5 (IQR zero-3), and 47/51 had RRMS. B-cell-depleting agents (ocrelizumab and rituximab) were given to 19 patients, another 19 were on immune cell traffickers (fingolimod and natalizumab), and 13 were on other DMT treatments (alemtuzumab, cladribine, interferon-beta, dimethyl fumarate, and teriflunomide). 43/51 of these patients experienced mild COVID-19, not requiring hospitalization. None of the subjects experienced MS relapses during infection. Two patients on rituximab had a moderate course of the illness, which required hospitalization for oxygen support, but did not need mechanical ventilation; the rest of the subjects remained asymptomatic. CONCLUSIONS: These findings suggest that DMT may not adversely affect the course of COVID-19 in MS patients; however, patients on B-cell-depleting agents trended toward a worse outcome.

Association between relapses, stress, and depression in people with multiple sclerosis during the COVID-19 pandemic.

BACKGROUND: Stress is a potential trigger for clinical and radiological activity in Multiple Sclerosis (MS). COVID-19 pandemic has been a relevant source of mental distress in people with MS (pwMS) and deeply impacted on disease management. OBJECTIVE: To investigate the association between stress, anxiety, depression, and risk of relapse during the COVID-19 pandemic. METHODS: From an electronic database used for clinical practice, we extracted data of relapsing-remitting (RR) or relapsing-progressive (RP) MS patients and calculated the annualized relapse rate (ARR) during 2019 and 2020. From 01/12/2020 to 30/12/2020, enrolled patients were invited to fill in a Google Forms survey to investigate depression, anxiety, stress, and Post-Traumatic Stress Disorder (PTSD). RESULTS: We selected 216 patients with RR or RP-MS to calculate ARR: compared to 2019, in 2020 there was a significant increase in ARR (p = 0.0142). Over 216 selected pwMS, 154 completed the survey. Matching the survey responses and incidence of relapses in 2020, there was a significant association between relapses and stress (p = 0.030) and relapses and depression (p = 0.011), but not between relapses and anxiety (p = 0.130) or PTSD (p = 0.279). CONCLUSIONS: Our results support the hypothesis that pandemic-related stress is associated to clinical exacerbations, both as a possible consequence of the COVID-19 impact on MS care.

Masked face recognition in patients with relapsing-remitting multiple sclerosis during the ongoing COVID-19 pandemic.

BACKGROUND: Face and facial expression recognition abilities have been frequently evaluated in the assessment of social cognition disorders in patients with MS. Investigation of the effect of new difficulties emerging in the field of face recognition with the widespread use of masks during the ongoing COVID-19 pandemic on patients with MS may make new contributions to the literature. MATERIAL AND METHODS: The study included 44 patients with relapsing-remitting MS (RRMSp) and 51 controls who were matched to the case group in terms of age and education level. The Benton face recognition test-short form (BFRT-sf), Beck Depression Inventory, a close-ended 13-item survey on face recognition difficulties due to mask use during the pandemic was administered to all groups. RESULTS: In the RRMSp, the mean disease duration was 8.2 ± 5.6, the mean EDSS score was 1.2 ± 1.0, and the mean MOCA test score was 27.23 ± 2.08. The mean BFRTsf was 19.9 ± 2.4 in the RRMSp and 21.6 ± 1.8 in the healthy controls.Twenty-five percent of RRMSp and 4% of the healthy controls required people to remove their masks to be able to recognize their faces. Improvement in face recognition difficulty over time was reported as 80% in the healthy controls and 34% in the RRMSp. CONCLUSION: RRMSp had worse performance in masked face recognition and required removal of the facial masks more often than healthy controls to recognize the faces. RRMS patients did not show as much improvement in recognizing masked faces over time according to the onset of the pandemic as healthy controls.

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.

Unexpected worsening of progressive multifocal leucoencephalopathy following COVID-19 pneumonia.

Progressive multifocal leucoencephalopathy is a serious side effect of natalizumab, a humanized monoclonal antibody approved for the treatment of multiple sclerosis. Here, we report a case of unexpected worsening of natalizumab-related progressive multifocal leucoencephalopathy following COVID-19. After natalizumab discontinuation, a slight neurological improvement was observed, but, two months later the patient was admitted to the hospital because of neurological deterioration and COVID-19 mild pneumonia. Except for SARS-CoV-2 infection, no other potential factors of neurological worsening were identified. Thus, we pose the hypothesis that SARS-CoV-2 was instrumental in the progressive multifocal leucoencephalopathy deterioration.

SARS-CoV-2/COVID-19 in multiple sclerosis patients receiving disease-modifying therapy.

At the end of 2019, the COVID-19 pandemic began, which at the time of writing continues to be a serious problem for many areas of medicine, including neurology. Since patients with multiple sclerosis (MS) often exhibit motor disability and receive disease-modifying therapy (DMT), which has an immunosuppressive effect, it is plausible that this will affect the susceptibility of MS patients to COVID-19, as well as the course of this disease. However, current data indicate that the use of DMT does not cause negative prognosis in COVID-19 sufferers, but the motor disability progression associated with MS does. In this study, we present the case reports of 4 patients with relapsing-remitting MS, who developed COVID-19, and despite the use of DMT the course of the disease was mild. Two patients were treated with dimethyl fumarate, one with Interferon ß1b and one with glatiramer acetate. One of the patients using dimethyl fumarate had lymphopenia. All patients had symptoms of COVID-19 from the nervous system, the most frequent being headache, which occurred in all patients. The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT.

Mental health status of relapsing-remitting multiple sclerosis Italian patients returning to work soon after the easing of lockdown during COVID-19 pandemic: A monocentric experience.

BACKGROUND: The prolonged lockdown related to COVID-19 pandemic determined disruption of lifestyle and social isolation. METHODS: To assess the mental health status of Relapsing-Remitting Multiple Sclerosis (RRMS) patients regularly followed at the MS center of Catania (Italy) and returning to work after the easing of lockdown during COVID-19 pandemic. Then, to identify any variables associated to psychological distress. RRMS patients returning to work during the COVID-19 pandemic were invited to answer a telephonic interview consisting of the administration of the Short-Screening-Scale for DSM IV (SSS-DSM-IV), the Depression, Anxiety, Stress Scale- 21 (DASS-21) and the Insomnia Severity Index (ISI). Other information was extracted from electronic medical records. RESULTS: Valid and complete interviews were obtained from 432 patients (response rate 64.3%). Out of them, 277 (64.1%) were female, mean age 40.4 (SD 12.4) years. One-hundred thirty-seven (31.7%) RRMS patients received a score ≥4 at the SSS-DSM-IV, indicating clinically significant PTSD-like symptoms. About DASS-21, moderate-to-severe anxiety was reported by 210 RRMS patients (48.6%), moderate-to-severe depression, and moderate-to-severe stress were respectively reported by 95 (22%) and 220 (50.9%) RRMS patients. Insomnia was reported by 128 patients (29.6%). Factors associated with major severity of symptoms were: marital status, previous diagnosis of mood disorders, switching/starting Disease-Modifying Therapies in the last 12 months, and a higher level of disability measured with Expanded Disability Status Scale (for all, p<.05). CONCLUSIONS: Our findings highlight the need to provide psychological support to MS patients facing the delicate phase of returning to work and to normal activities.

Mild or no COVID-19 symptoms in cladribine-treated multiple sclerosis: Two cases and implications for clinical practice.

BACKGROUND: The use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) could affect COVID-19 outcomes by modulating the immune response, which, in turn, might favor viral replication and/or confer protection from COVID-19 induced inflammatory response CASE REPORT: We report on two MS patients treated with cladribine, with heterogeneous demographics and clinical features, who developed mild or no symptoms from COVID-19 and produced anti-SARS-CoV-2 antibodies, notwithstanding low lymphocyte levels. IMPLICATIONS: Benign COVID-19 clinical course and anti-SARS-CoV-2 antibody production can occur in MS patients with lymphopenia, suggesting the possibility to respond to COVID-19 vaccination, once available, in this vulnerable population.

COVID-19 pneumonia in a multiple sclerosis patient with severe lymphopenia due to recent cladribine treatment.

BACKGROUND: Most cases of COVID-19 are considered mild, but patients with immunosuppressant treatment might be prone to severe courses of disease. Expert panels advise to delay treatment with cell-depleting MS therapies during the COVID-19 pandemic. METHODS: We report a case of a patient with relapsing-remitting multiple sclerosis who developed COVID-19 pneumonia 2 weeks after the first week of cladribine therapy. RESULTS: Despite a severe lymphopenia (absolute lymphocyte count 240/µL), the patient had a moderate course of COVID-19. CONCLUSION: Apart from maximal supportive treatment, this could be due to cladribine reducing inflammatory response, which probably contributes considerably to severe courses of COVID-19 pneumonia.

COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach.

BACKGROUND: The novel Coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has generated a global pandemic impacting over 200 countries around the world. Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons. In this scenario, neurologists are particularly involved into considering even more specific therapeutic strategies according to the available data during the pandemic. In particular, MS patients are usually receiving disease-modifying therapies (DMTs) with immunosuppressant or immunomodulatory effects, which increase the risk of infections and morbidity, compared with the general population. Development of PML or other serious opportunistic infections during treatment with natalizumab forces to consider whether de-risking strategies are needed in this particular context and how to manage a high-efficacy treatment. METHODS: In this paper we report on a patient treated with natalizumab for relapsing MS who developed COVID-19 and recovered in a few days without complications. RESULTS: After recovery natalizumab has been administered in the window of the extended interval dosing (EID), without reporting any worsening or new symptoms. DISCUSSION: This case supports the opportunity to avoid discontinuing or delaying the retreatment over 8 weeks in patients recovered from a recent COVID-19.