ABSTRACT
Background: During COVID-19 pandemic second line disease modifying therapies (DMTs) for multiple sclerosis (MS), have been frequently postponed because of the epidemiological situation and the lack of safety information. Objective(s): To evaluate clinical implications of delaying ocrelizumab dosing in MS. Aim(s): To assess the occurrence of clinical relapses, disability worsening and neuroradiological disease activity in MS patients receiving extended interval dosing ocrelizumab in a real-world setting. Method(s): Data from 90 MS patients (65 RRMS, 25 PPMS) who underwent ocrelizumab dose delay have been retrospectively obtained: in particular MS history, neurological examinations, white blood cells count (particularly lymphocyte subsets) and neuroradiological data have been collected. Result(s): Enrolled patients have been followed up for a mean of 9.5+/-2.8 months after ocrelizumab dose delay (mean dosing interval 7.67+/-0.79 months). None of our 65 RRMS patients had clinical relapses, nor rapid disability worsening has been experienced by the PPMS cohort. Pre-infusion CD19+/CD20+ lymphocyte subset was available in 75/90 patients, with 18/75 patients showing significant B cells repopulation (defined as CD19+/CD20+ >= 1.0%). MRI data were available in 47/90 patients, with 5/47 patients showing evidence of neuroradiological disease activity (mild in all reported cases and in the absence of any correlation with B cells repopulation). Conclusion(s): Our data suggest ocrelizumab dose delay is generally safe in MS patients. Experiences during COVID-19 pandemic could be a starting point towards a more personalized scheduling of ocrelizumab therapy.
ABSTRACT
Introduction: The SARS-CoV-2 pandemic has raised, among others, a particular concern for people taking immune-suppressants. The Italian MS Foundation (FISM), Neuroimmunology Association (AINI), Neurological Society (SIN), and MS Registry have constituted an Alliance to tackle these issues. In the field of multiple sclerosis, several reports have suggested a higher risk of infection and an increased severity of the disease in persons treated with anti-CD20 monoclonal antibody. Serological investigations, showing a blunted production of anti-SARS-CoV-2 antibodies, questioned the usefulness of vaccination in these subjects, without, however, considering T cell responses. Objectives and Aims: To investigate antiviral T cell responses after infection with SARS-CoV-2 in persons with MS (pwMS) treated with Ocrevus.Control groups include pwMS treated with Ocrevus without SARS-CoV-2 infection, persons without MS with SARS-CoV-2 infection, and healthy individuals vaccinated or not with BNT16b2. Methods: Blood samples were collected and processed to isolate PBMCs, that were then stored frozen. PBMCs were stimulated with SARS-CoV-2 peptide pools and T cell reactivity was assessed by ELISPOT for IFNg detection, and by multiparametric FACS analyses for assessment and characterization of T cell activation. Results: ELISPOT assay against the spike and the N protein of SARS-CoV-2 displayed specific T cell reactivity in 80% pwMS treated with Ocrevus and infected by SARS-CoV-2, similar to infected persons without MS. FACS analysis following stimulation with SARS-CoV-2 peptide pools, showed the presence of activation-induced markers (AIM) in both CD4 and CD8 T cell subsets in 96% and 92% of these individuals, respectively. CD4 AIM+ cells were mostly central and effector memory cells, while CD8 cells were largely CD45RA+ terminally differentiated effectors (TEMRA) and poised for cytotoxicity, with a significant fraction of naïve cells. Within naïve AIM+ CD4 and CD8 cells we detected memory stem cells, suggesting the acquisition of long-term memory and protection from reinfection. COVID-19- recovered pwMS treated with Ocrevus had T cell responses comparable to healthy individuals vaccinated with BNT162b2, particularly concerning the ability to produce cytokines. Conclusions: B-cell depletion using Ocrevus does not impair the development of anti-SARS-CoV-2 T cell responses. Multistakeholder initiatives are mandatory to rapidly obtain unbiased clinically crucial information.
ABSTRACT
Introduction: MS patients affected by SARS-CoV-2 disease may present with a wide pattern of symptoms, not always suggestive of the severity of infection. A recent study has shown that main symptoms of Covid-19 can be grouped in seven different clusters. Risk and protective factors for their occurrence in MS patients has never been investigated. Objectives: To identify the most common symptoms of Covid-19 that are part of specific clusters in MS patients and evaluate all factors associated with their manifestation. Methods: As part of the MuSC-19 Italian project, all data were extracted from a dedicated web-based platform that allows researchers to evaluate the impact of Covid-19 on people affected by MS. After having tested the degree of agreement between different types of symptoms (Cohen's k), univariate and multivariate logistic regression models were applied to identify predicting factors for each group. Results: 1554 MS patients with confirmed Covid-19 and presenting at least one symptom referred to a specific cluster were analyzed. Patients presented nearly three groups of symptoms (mean: 2.8). The most common include fever/chills/rigor/fatigue/ cough (87%), followed by ageusia/anosmia (46%). Smoking habit was the most confirmed risk factor for developing a wide range of symptoms: common cold-like symptoms (OR:1.6, 95%CI:1.3- 2.1;p<0.001), joint and muscle pain (OR:1.3, 95%CI:1.1-1.7;p=0.037), gastrointestinal problems (OR:1.3, 95%CI: 1.1-1.7;p = 0.029), and loss of smell/taste (OR:1.4, 95%CI: 1.07-1.72;p=0.013). Smoking was confirmed also as risk factor for increasing the number of symptoms (OR:1.5, 95%CI:1.2-1.8;p<0.001), together with alcohol use (OR:1.25, 95%CI:1.1-1.5;p=0.021) and with assumption of anti-CD20 therapies (OR:1.7, 95%CI:1.2-2.5;p=0.004). Males have a lower risk for developing a major number of symptoms (OR:0.8, 95%CI:0.6 - 0.9;p=0.006). Finally, a lower EDSS was associated to a slight increment of symptoms, probably due to an already underlying presence of some common symptoms in most critical MS patients, which consequently were not reported (OR:0.9, 95%CI:0.8-0.9;p=0.005). Conclusions: Knowing possible risk factors and modifying some lifestyle behaviors might minimize the occurrence of Covid-19 symptoms. Anyway, further studies are needed for confirming these findings, and an additional follow up study on the presence of persistent symptoms after apparent Covid-19 resolution may help to better understand all possible risk factors.
ABSTRACT
Introduction: Onco-hematological patients, specifically those treated with hematopoietic stem cell transplantation (HSCT) [2], are particularly at risk of severe acute respiratory syndrome due to Coronavirus-2 (SARS-CoV-2). Conversely, evidences regarding Coronavirus Disease 2019 (COVID-19) in aggressive multiple sclerosis (MS) treated with autologous HSCT (aHSCT) are not available. At pandemic start, and in the absence of data, European Society for Blood and Marrow transplantation/Autoimmune Disease Working Party (EBMT/ADWP) suggested delaying not life-sparing HSCT. Aim: To describe cases of COVID-19 in a population of aggressive MS treated with aHSCT. Materials and Methods: Data were collected from 4 centers (march-2020 to april-2021). Patients' health-status was periodically monitored by phonecall. Patients transplanted within a 12-month period were asked to maintain a strict home-isolation. Those transplanted from longer than 12 months were asked to keep safe behaviour, as recommended by EBMT/ADWP. Results: We recorded 5 cases out of 70 patients. At COVID-19 time, mean (standard deviation) disease duration (dd) was 12.0 (±4.9) years and median expanded disability status scale (EDSS) was 4.5 (range 3.0-7.5). Mean time from aHSCT was 24.7 (±9.8) months (range 12.9-37.0). All patients presented normal lymphocyte values besides one with grade-two lymphopenia (617.0 cc/ mm
ABSTRACT
Introduction: Studies have pointed out that air pollution longterm exposure may play a role in the severity and prognosis of SARS-CoV-2 infections. Additionally, air pollution has been associated to MS prevalence and course. However, the role of air pollution in COVID-19 severity has never been explored specifically among MS patients. Aims: To explore the association between air pollution assessed by PM2.5 levels and COVID-19 severity among MS patients. Methods: Demographic and clinical characteristics as well as data about Covid-19 severity were extracted from an Italian webbased platform (Musc-19 project) containing clinician-reported data from 118 Italian MS centers. PM2.5 ground-level concentrations were derived from air quality model results, as provided by the 'Copernicus Atmospheric Monitoring Service' (CAMS). Ordered logistic regression models were used to assess the association between PM2.5 (continuous and in tertiles) and Covid-19 prognosis (defined on three levels as mild course, hospitalization, and intensive care unit (ICU) admission or death) while controlling for possible confounders. Results: PM2.5 concentrations were available for 1517 MS patients, of whom 1321(87%) were classified as mild Covid-19 cases, 172(11%) were hospitalized and 24(2%) were admitted to ICU or died. Higher concentrations of PM2.5 were associated with increased odds of developing a worst Covid-19 prognosis (10-unit increase in PM2.5: OR(95% CI)=1.76(1.16-2.67) p-value=0.008;3rd vs 1st tertile: OR(95% CI)=1.74(1.17-2.59) p-value=0.006). Results remained consistent when we included only the Covid-19 cases confirmed by a nasopharyngeal swab (N=1087). Conclusions: Higher concentrations of PM2.5 are associated with Covid-19 severity among MS patients. Further studies are needed to evaluate the impact of other air pollutants, but urgent measures to reduce air pollution must be surely adopted.
ABSTRACT
Introduction: It is still debated whether Multiple Sclerosis (MS) patients are at high-risk of COVID-19 because of their life style, disease- or treatments-associated immune alterations. We compared features of MS patients with COVID-19 infection (MS-COVID) to those of residency-, age-, sex- and treatmentmatched MS controls (MS-NCOVID). Moreover, the severity of COVID-19 infection was assessed in MS-COVID patients and their cohabitants. Aims: Evaluate epidemiologic factors of MS patients who developed COVID-19 infection. Evaluate wether COVID-19 infection severity was different between patients and their cohabitants Methods: So far, we have enrolled 25 MS-COVID and 104 MS-NCOVID patients. Neurological examination, premorbid laboratory tests, anthropometric variables (height, weight and BMI), life-style habits (smoke, alcohol intake, diet), workingactivity and living conditions (number of cohabitants, schoolaged children) were assessed. COVID-19 severity was evaluated in terms of fever (magnitude, duration), radiological pneumonia and typical symptoms. Results: Clinical and anthropometric features, life-style habits and living conditions were similar between MS-COVID and MS-NCOVID patients. However, they differed in terms of working activity, with lower rate of unemployment (7.1% vs 23.4%) and higher rate of team-working (61.5% vs 26.5%) in the MS-COVID group (p<0.01). Furthermore, MS-COVID patients had lower premorbid vitamin D levels (31 vs 40 ng/ml p=0.048) and higher neutrophils count (3803 vs 3182 cells/ul, p=0.046). Disease course was similar between MS-COVID patients and their cohabitants with fever, ageusia and anosmia being the most common symptoms. Fever and radiologic signs of pneumonia were also comparable. Conclusion: Working-activity, lower vitamin D levels and higher neutrophil count seem to be associated with the risk of COVID-19 infection in MS patients. The burden of COVID-19 disease was comparable between MS patients and their cohabitants.
ABSTRACT
Introduction: Extending natalizumab (NTZ) dosing in patients with Multiple Sclerosis (MS) may increase the risk of disease reactivation. Nevertheless, evidence is lacking on the safety of reinfusion during active Sars-Cov-2 infection in patients needing retreatment. Aims and Objective: To describe the clinical outcome of patients with MS (PwMS) receiving NTZ redosing during active Sars- Cov-2 infection. Methods: 14 NTZ treated PwMS (mean age 39 years, females 11, median number of NTZ infusions 47) from 6 Italian MS centers with diagnosis of Sars-Cov2 infection confirmed by positive RT-PCR nasopharyngeal swab were retrospectively included.The main variables analyzed were baseline characteristics, outcome of infection after reinfusion, hospitalization, time to negative swab and occurrence of neurological complications. Results: All patients had symptomatic COVID-19 (13 mild, 1 moderate). None required respiratory support or hospitalization. At the time of NTZ reinfusion (median interval 52 days from the previous infusion), 14/14 had a positive molecular test performed within a median time of 3 days (0-11) and 4/14 were symptomatic. After infusion, none complained of worsening of COVID-19 symptoms or reported neurological complications. Median time to negative swab was 14,5 days (2-36) from infusion and 34,5 days (12-62) from first positive swab. Conclusions: In response to primary concerns about potential worsening of COVID-19 symptoms, due to the neuro and gastrointestinal tropism of Sars-Cov-2, our data support the safety of NTZ redosing in patients with active infection;therefore, in this condition, NTZ should not be interrupted/delayed, in order to minimize the risk of relapses.
ABSTRACT
Objective: To describe the effect of disease modifying therapies (DMT) on Covid-19 severity in a large cohort of Italian patients with Covid-19 and multiple sclerosis (MS). Background: We previously presented data from a nationwide study of persons with MS with suspected or confirmed Covid-19, collected from March 2020. In June we started collecting also asymptomatic patients, when serological tests started to be routinely done. Design/Methods: This was a retrospective multi-center observational study. We defined Covid-19 severity as a 4-level variable: Level 1=asymptomatic, level 2=symptomatic without signs of pneumonia, level 3=radiologically defined pneumonia or hospitalization, level 4=intensive care unit (ICU) or death. We analysed the impact of baseline variables on this outcome by a multivariable ordinal logistic model quantifying the association by Odds Ratio (OR). Results: On October 12, we enrolled 902 MS patients, 298 (33%) with confirmed and 604 (67%) with suspected Covid-19;37 (4%) were asymptomatic. The number of ICU/deaths were 8/95 (8%) among those treated with anti-CD20 therapies (mean age=41 years), 0/84 (0%) among those treated with Interferon (mean age=47 years) and 37/723 (5%) among those treated with other drugs (mean age=43 years). Among the 37 asymptomatic patients, 7/84 (8.3%) were in Interferon, 1/95 (1.1%) was on anti-CD20 and 29/723 (4%) were on other drugs. At multivariable analysis, independent risk factors for a severe Covid-19 were age (OR=1.05, p<0.001), EDSS(OR=1.13, p=0.02), Male sex(OR=1.44, p=0.057) and DMT used: Treatment with anti-CD20 (Ocrelizumab or Rituximab) increased the risk (OR=1.99, p=0.035) and treatment with Interferon reduced the risk (OR=0.48, p=0.05) of severe Covid-19 as compared to treatment with DMF, used as the reference DMT. Conclusions: This analysis confirms on a larger population the increase of risk of severe Covid-19 of anti-CD20 therapies and highlights the protective role of Interferon. Data on asymptomatic patients are rapidly accumulating and will provide useful information about this.
ABSTRACT
Background and aims: It is still debated whether Multiple Sclerosis (MS) patients are at high-risk of COVID-19 because of their life style, disease-or treatments-associated immune alterations. We compared features of MS patients with COVID-19 infection (MS-COVID) to those of residency-, age-, sex-and treatment-matched MS controls (MS-NCOVID). Moreover, the severity of COVID-19 infection was assessed in MS-COVID patients and their cohabitants. Methods: So far, we have enrolled 25 MS-COVID and 104 MS-NCOVID patients. Neurological examination, premorbid laboratory tests, anthropometric variables (height, weight and BMI), life-style habits (smoke, alcohol intake, diet), working-activity and living conditions (number of cohabitants, school-aged children) were assessed. COVID-19 severity was evaluated in terms of fever (magnitude, duration), radiological pneumonia and typical symptoms. Results: Clinical and anthropometric features, life-style habits and living conditions were similar between MS-COVID and MS-NCOVID patients. However, they differed in terms of working activity, with lower rate of unemployment (7.1% vs 23.4%) and higher rate of teamworking (61.5% vs 26.5%) in the MS-COVID group (p<0.01). Furthermore, MS-COVID patients had lower premorbid vitamin D levels (31 vs 40ng/ml p=0.048) and higher neutrophils count (3,803 vs 3,182 cells/ul, p=0.046). Disease course was similar between MS-COVID patients and their cohabitants with fever, ageusia and anosmia being the most common symptoms. Fever and radiologic signs of pneumonia were also comparable. Conclusion: Working-activity, lower vitamin D levels and higher neutrophil count seem to be associated with the risk of COVID-19 infection in MS patients. The burden of COVID-19 disease was comparable between MS patients and their cohabitants.
ABSTRACT
Background: Telemedicine is a live communication between patients and physicians through different technological tools. It became fundamental during COVID-19 pandemic to keep on taking care of patients in more medical fields than before. Given the chance for telemedicine to become a pivotal part of neurological routine practice, we investigated patients and neurologists satisfaction about this tool. Objectives: This survey aimed to understand satisfactionabout telemedicine during pandemic and its possible use in the future outside pandemic Methods: We administered a brief survey to a cohort of Multiple Sclerosis (MS) patients and their neurologists at MS center of San Raffaele Hospital, Milan. Demographic and clinical data (EDSS, treatment) were collected. Results: 151 patients filled out the survey: 75% females;mean age 42.2yy (18-73);median EDSS 1.5 (0-7). Treatments were almost equally distributed across first and second-line drugs (10% interferon, 10% glatiramer acetate, 14% teriflunomide, 22% dimethylfumarate, 23% fingolimod, 3% cladribine, 8% alemtuzumab, 10% ocrelizumab). 87% of patients appreciated telemedicine during pandemic;10% had a positive opinion but with a need for traditional evaluations, while 3% were not satisfied. Considering the possible routine use of telemedicine outside the pandemic, 82% firmly stated the importance of traditional evaluations. In particular, 44% would alternate in person and remote visits, while 38% strongly preferred traditional ones. Among the latters, the main reasons were the need for human empathy with the neurologist and the feeling that traditional evaluations may lead to better clinical outcomes. The remaining 18% would always use telemedicine except in the case of acute events. Neurologists and residents (n=18) were inquired about telemedicine: no one would use it as the only tool, 33% would alternate it with traditional practice and 67% would use it only in special contexts. Conclusions: In our survey, both patients and neurologists recognized the importance of telemedicine during a pandemic. Patients more than physicians seemed ready to use it in everyday clinical practice. These data may be biased by a still ongoing patients fear and physicians lack of confidence in this multifaceted tool. The pandemic spurred the development of institutional telematic platforms capable of providing legal protection and traceability of visits and communication between patients and physicians. So far, we can conclude that telemedicine is a useful tool to overcome space-time limits, giving the best care to all patients in any condition. However, it cannot replace but only integrate traditional medicine.