ABSTRACT
Background: High-efficacy (HE) disease-modifying therapies (DMTs) for Multiple Sclerosis (MS), such as anti-CD20 monoclonal antibodies - i.e., Ocrelizumab (OCR) and Rituximab - may worsen COVID-19 course. Preliminary data suggest that two doses of mRNA COVID-19 vaccine (RNA-Vax) reduce the risk of breakthrough/severe COVID-19 in patients with MS (pwMS) under treatment with HE-DMTs. Little is known about the protective effect of a third booster dose of RNA-Vax in pwMS treated with most commonly used HE-DMTs, such as Natalizumab (NTZ), Fingolimod (FNG), and OCR. Aim(s): To compare COVID-19 course and outcomes in pwMS on NTZ, FNG, and OCR after receiving the third dose of RNA-Vax. Method(s): Inclusion criteria were: >18 years old, being treated with NTZ/OCR/FNG since the first vaccine dose, diagnosis of COVID-19 after a third booster dose of RNA-Vax, not being treated with steroids within the month prior to any vaccine dose or COVID-19. Result(s): 232 pwMS (63 NTZ, 106 OCR, 63 FNG) from 17 Italian MS centers were included in the analysis. pwMS on NTZ (37+/-9) were younger than those on OCR (42+/-10, p=0.026) and FNG (43+/-11, p=0.006);EDSS was higher in pwMS on OCR (3.0, IQR=1.5-5.5) than those on FNG (2.0, IQR=1.0-3.0, p=0.017). COVID-19 was diagnosed 65+/-41 days after receiving the third booster dose. PwMS on OCR compared with those on NTZ showed more frequently (p<0.02-0.001): fever >38degreeC (53.8% vs 20.6%), cough (67% vs 36.5%), dyspnea (18.9% vs 3.2%), longer symptoms duration (9.5+/-8.7 vs 6+/-4.6 days), use of NSAIDs (74.5% vs 52.4%), oxygen (7.5% vs 0%), antibiotics (45.3% vs 14.3%). PwMS on OCR compared with those on FNG needed more frequently the use of oxygen (7.5% vs 1.6%, p=0.002). PwMS on FNG compared with those on NTZ showed more frequently (p<0.03-0.002): fever >38degreeC (39.7% vs 20.6%), cough (65.1% vs 36.5%), dyspnea (15.9% vs 3.2%). There were no differences between the 3 groups of pwMS regarding: COVID-19 treatment with steroids or monoclonal antibodies, hospitalization, and full recovery or death (0%). Discussion and Conclusion(s): Breakthrough COVID-19 after a third booster dose of RNA-Vax was more symptomatic in pwMS on OCR and FNG than those on NTZ. Nevertheless, no deaths were reported and the Covid-19 course in terms of full recovery and hospitalization rates was not different across different HE-DMTs. These results support the efficacy of a third booster dose of RNA-Vax in preventing severe COVID-19 (with hospitalization/ death) in pwMS treated with most common HE-DMTs.
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.
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.