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: 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.