Project description:Multiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, there is little data identifying clinical characteristics of MS associated with worse COVID-19 outcomes. Therefore, we conducted a multicenter prospective cohort study looking at the outcomes of 40 MS patients with confirmed COVID-19. Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor, and most severe was defined as requiring intensive care unit admission and/or death. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P = 0.0121, P = 0.0373). There was differing prevalence of progressive MS phenotype in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P = 0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P = 0.00435) of moderate course-patients and 2/6(33.3%, P = 0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P = 0.123). MS patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive phenotype, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.
Project description:(1) Background: To report and analyze the presence of residual symptoms after SARS-CoV-2 infection among Polish patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). (2) Methods: The study included 426 individuals with MS treated with DMTs and confirmed SARS-CoV-2 infection from 12 Polish MS centers. The data were collected through to 31 May 2021. The information included demographics, specific MS characteristics, course of SARS-CoV-2 infection, and residual (general and neurological) symptoms lasting more than four and 12 weeks after the initial infection. The results were obtained using maximum likelihood estimates for odds ratio and logistic regression. (3) Results: A total of 44.84% patients with MS reported symptoms lasting between four and 12 weeks after the initial infection; 24.41% people had symptoms that resolved up to 12 weeks, and 20.42% patients had symptoms that lasted over 12 weeks. The most common symptoms were: fatigue, disturbance of concentration, attention, and memory, cognitive complaints, and headache. None of the DMTs were predisposed to the development of residual symptoms after the initial infection. A total of 11.97% of patients had relapse three months prior or after SARS-CoV-2 infection. (4) Conclusion: Almost half of individuals with MS treated with different DMTs had residual symptoms after SARS-CoV-2 infection. None of the DMTs raised the probability of developing post-acute COVID symptoms.
Project description:We conducted a retrospective cohort study in Kaiser Permanente Southern California from 1 January 2020 to 30 September 2020. We found that rituximab-treated persons with multiple sclerosis (pwMS, n = 1895) were more likely be hospitalized (n = 8, 33.3%), but not die (n = 0) from COVID-19, compared to the 4.81 million non-MS population (5.8% and 1.4%, respectively). Time in months (adjusted OR = 0.32, 95% CI = 0.15-0.69, p = 0.0033) and receiving 1000 mg compared to lower doses at last infusion (adjusted OR = 6.28, 95% CI = 1.38-28.5, p = 0.0173) were independent predictors of COVID-19 severity. Rituximab-treated pwMS should be counseled to take extra precautions in the 5 months following each infusion. Using extended dosing intervals and lower doses could be considered.
Project description:The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups.
Project description:Introduction Since the declaration of COVID-19 pandemic, several cases of demyelination of both peripheral and central nervous systems have been reported. The association of viral infection and the development of CNS demyelination has long been studied, and this link has recently been reported following SARS-CoV-2 infection as well. Case report We report a case of a 36-year-old male who developed CNS demyelinating disease, that fulfilled the diagnostic criteria of multiple sclerosis (MS), 2 months after laboratory-confirmed infection with SARS-CoV-2. Conclusion To our knowledge, this is the second published case report of MS in association with COVID-19 infection, and the first case from Middle East and North Africa (MENA) region, adding to the growing literature of a probable causal relationship between SARS‐CoV‐2 infection and the development of MS.
Project description:BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread and developed as a pandemic threatening global health. Patients with multiple sclerosis (MS)-an autoimmune demyelinating inflammatory disease of the central nervous system (CNS)-are predominantly treated with immunomodulatory/immunosuppressive disease-modifying therapies (DMTs), which can increase the risk of infection. Therefore, there is concern that these patients may have a higher risk of COVID-19. In response to growing concerns of neurologists and patients, this study aimed to determine the prevalence, severity, and possible complications of COVID-19 infection in patients with MS in Saudi Arabia (SA).MethodsIn this prospective cohort study, demographic and clinical data were obtained from patients residing in SA with MS who had a positive result for COVID-19 per reverse transcription-polymerase chain reaction test or viral gene sequencing, using respiratory or plasma samples. Comparison of COVID-19 severity groups was performed using one-way ANOVA or Kruskal-Wallis test for numerical variables and Chi-squared test for categorical variables.ResultsSeventy patients with MS and COVID-19 (71% female) were included in this analysis. Of the 53 (75.7%) patients receiving a DMT at the time of COVID-19 infection, the most frequently used DMTs were fingolimod (25%) and interferon-beta (25%). Nine (13%) patients had MS relapse and were treated with intravenous methylprednisolone in the four weeks before COVID-19 infection. The most common symptoms at the peak of COVID-19 infection were fever (46%), fatigue (37%), and headache (36%). Symptoms lasted for a mean duration of 8.7 days; all symptomatic patients recovered and no deaths were reported. COVID-19 severity was categorized in three groups: asymptomatic (n = 12), mild-not requiring hospitalization (n = 48), and requiring hospitalization (n = 10; two of whom were admitted to the intensive care unit [ICU]). Between the three groups, comparison of age, body mass index , Expanded Disability Severity Score , MS disease duration, and DMT use at the time of infection showed no significant differences. A higher percentage of patients who were admitted to hospital or the ICU (40%; p = 0.026) presented with an MS relapse within the prior four weeks compared with those who were asymptomatic or had a mild infection (both 8.3%).ConclusionThese findings present a reassuring picture regarding COVID-19 infection in patients with MS. However, patients with MS who have had a relapse in the preceding four weeks (requiring glucocorticoid treatment) may have an increased risk of severe COVID-19.
Project description:COVID-19 infection caused by the newly discovered coronavirus severe acute respiratory distress syndrome virus-19 (SARS-CoV-2) has become a pandemic issue across the globe. There are currently many investigations taking place to look for specific, safe and potent anti-viral agents. Upon transmission and entry into the human body, SARS-CoV-2 triggers multiple immune players to be involved in the fight against the viral infection. Amongst these immune cells are NK cells that possess robust antiviral activity, and which do not require prior sensitization. However, NK cell count and activity were found to be impaired in COVID-19 patients and hence, could become a potential therapeutic target for COVID-19. Several drugs, including glatiramer acetate (GA), vitamin D3, dimethyl fumarate (DMF), monomethyl fumarate (MMF), natalizumab, ocrelizumab, and IFN-β, among others have been previously described to increase the biological activities of NK cells especially their cytolytic potential as reported by upregulation of CD107a, and the release of perforin and granzymes. In this review, we propose that such drugs could potentially restore NK cell activity allowing individuals to be more protective against COVID-19 infection and its complications.
Project description:Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.