Outcomes and risk factors associated with SARS-CoV-2 infection in a North American registry of patients with multiple sclerosis

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections. Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS. Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death. Data collection began April 1, 2020, and is ongoing. Exposures: Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19. Main Outcomes and Measures: Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death. Results: Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7%]), were female (1202 [74.0%]), and had relapsing-remitting MS (1255 [80.4%]). A total of 996 patients (61.5%) were non-Hispanic White, 337 (20.8%) were Black, and 190 (11.7%) were Hispanic/Latinx. The mean (SD) age was 47.7 (13.2) years, and 797 (49.5%) had 1 or more comorbidity. The overall mortality rate was 3.3% (95% CI, 2.5%-4.3%). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors (nonambulatory: hospitalization only, odds ratio [OR], 2.8 [95% CI, 1.6-4.8]; intensive care unit/required ventilator support, OR, 3.5 [95% CI, 1.6-7.8]; death, OR, 25.4 [95% CI, 9.3-69.1]; age [every 10 years]: hospitalization only, OR, 1.3 [95% CI, 1.1-1.6]; intensive care unit/required ventilator support, OR, 1.3 [95% CI, 0.99-1.7]; death, OR, 1.8 [95% CI, 1.2-2.6]). Conclusions and Relevance: In this registry-based cross-sectional study, increased disability was independently associated with worse clinical severity including death from COVID-19. Other risk factors for worse outcomes included older age, Black race, cardiovascular comorbidities, and recent treatment with corticosteroids. Knowledge of these risk factors may improve the treatment of patients with MS and COVID-19 by helping clinicians identify patients requiring more intense monitoring or COVID-19 treatment

Cytokine regulation of tumor necrosis factor receptor messenger RNA in mouse cerebromicrovascular endothelial cells

Vita.Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) with pathophysiologic features similar to multiple sclerosis (MS). In both diseases circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis. The pluripotent cytokine tumor necrosis factors (TN-F-a), has been implicated to play an important role in the pathogenesis of MS and EAE. TNIF-(X may act by promoting leukocyte adhesion to the cerebrovascular endothelium (CVE) and migration of inflammatory cells into the CNS. The receptors for TNF (TNFR) on CVE cells may be a potential target for therapeutic intervention. In order to examine the role of the TNF receptors, CVE cell lines were established from EAE susceptible (SJL/J) and resistant (BALB/c) inbred strains of mice. The lines retained endothelial cell specific markers and remained diploid through 16 passages. An endothelial cell specific CDNA library was synthesized and the 55 kD and 75 kD TNF receptors were cloned and sequenced. Quantitative northern blotting was used to determine the effects of IIFN-Y, IL-1, and TNF-(X on CVE cell TNFR MRNA regulation using TNFR specific hybridization probes. IFN-Y and IL- 1 were found to increase niRNA transcription of the 55 kD and 75 kD TNFR. The 55 kD receptor was more sensitive to up-regulation by IFN-,y, whereas the 75 kD receptor was more sensitive to up-regulation by EL- 1. IL- 1 and TNF-(X were found to act in a cooperative manner to up-regulate MRNA for both the 55kD and 75 kD receptors. No significant differences were found in cytokine induced TNFR MRNA levels between SJL/J and BALB/c CVE that might explain differences in EAE susceptibility. However, in studies of mast cells derived from these mouse strains, it was found that SJL/J mast cells store and release significantly more TNF-A and histamine than BALB/c mast cells. These studies suggest that the levels of cytokines, such as TN-F-a, released by CNS associated mast cells, may contribute to susceptibility differences in murine EAE

Cytokine regulation of tumor necrosis factor receptor messenger RNA in mouse cerebromicrovascular endothelial cells

Vita.Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) with pathophysiologic features similar to multiple sclerosis (MS). In both diseases circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis. The pluripotent cytokine tumor necrosis factors (TN-F-a), has been implicated to play an important role in the pathogenesis of MS and EAE. TNIF-(X may act by promoting leukocyte adhesion to the cerebrovascular endothelium (CVE) and migration of inflammatory cells into the CNS. The receptors for TNF (TNFR) on CVE cells may be a potential target for therapeutic intervention. In order to examine the role of the TNF receptors, CVE cell lines were established from EAE susceptible (SJL/J) and resistant (BALB/c) inbred strains of mice. The lines retained endothelial cell specific markers and remained diploid through 16 passages. An endothelial cell specific CDNA library was synthesized and the 55 kD and 75 kD TNF receptors were cloned and sequenced. Quantitative northern blotting was used to determine the effects of IIFN-Y, IL-1, and TNF-(X on CVE cell TNFR MRNA regulation using TNFR specific hybridization probes. IFN-Y and IL- 1 were found to increase niRNA transcription of the 55 kD and 75 kD TNFR. The 55 kD receptor was more sensitive to up-regulation by IFN-,y, whereas the 75 kD receptor was more sensitive to up-regulation by EL- 1. IL- 1 and TNF-(X were found to act in a cooperative manner to up-regulate MRNA for both the 55kD and 75 kD receptors. No significant differences were found in cytokine induced TNFR MRNA levels between SJL/J and BALB/c CVE that might explain differences in EAE susceptibility. However, in studies of mast cells derived from these mouse strains, it was found that SJL/J mast cells store and release significantly more TNF-A and histamine than BALB/c mast cells. These studies suggest that the levels of cytokines, such as TN-F-a, released by CNS associated mast cells, may contribute to susceptibility differences in murine EAE

Quality of life and work productivity impairment among psoriasis patients: findings from the National Psoriasis Foundation survey data 2003-2011.

OBJECTIVE: To ascertain impairment in quality of life and work productivity among patients with psoriasis and psoriatic arthritis. DESIGN: From 2003 through 2011, the National Psoriasis Foundation collected survey data from patients with psoriasis and psoriatic arthritis via email and telephone correspondences. SETTING: Survey data were collected from psoriasis and psoriatic arthritis patients in the general community in the U.S. MAIN OUTCOME MEASURES: Quality of life focusing on emotional impact (anger, frustration, helplessness, etc.) and physical impact (pain, pruritus, physical irritation, etc.); employment status. PATIENTS: The surveys were performed through random sampling of participants from a database of over 75,000 patients. RESULTS: From 2003 to 2011, 5,604 patients completed the surveys. Psoriasis and psoriatic arthritis affected overall emotional wellbeing in 88% of patients, and they interfered with enjoyment of life in 82%. Most patients reported experiencing anger (89%), frustration (89%), helplessness (87%), embarrassment (87%), and self-consciousness (89%). Many patients also actively concealed physical manifestations of their diseases (83%), and experienced pain (83%) and pruritus (93%) regularly. Of note, 12% of patients were unemployed, and 11% worked part-time. Among unemployed patients, 92% cited psoriasis and/or psoriatic arthritis as the sole reasons for not working. Among working patients, 49% missed work days regularly due to psoriasis. Compared to patients with mild psoriasis, patients with severe psoriasis have 1.8 times greater odds to be unemployed after adjusting for age and gender (Adjusted OR = 1.7, 95% CI 1.4-2.3). CONCLUSION: Patients with psoriasis and psoriatic arthritis continue to experience significant impairment of quality of life and work productivity

Reasons for Not Working among Psoriasis Patients.

<p>Reasons for Not Working among Psoriasis Patients.</p

Unemployment and Psoriasis Severity.

<p>Unemployment and Psoriasis Severity.</p

Employment Status among Psoriasis Patients.

<p>Employment Status among Psoriasis Patients.</p

COVID-19 in patients with neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody disease in North America: From the COViMS Registry

BACKGROUND AND OBJECTIVE: To describe the impact of coronavirus disease 2019 (COVID-19) on people with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). METHODS: The COVID-19 Infections in Multiple Sclerosis (MS) and Related Diseases (COViMS) Registry collected data on North American patients with MS and related diseases with laboratory-positive or highly suspected SARS-CoV-2 infection. Deidentified data were entered into a web-based registry by health care providers. Data were analyzed using RESULTS: As of June 7, 2021, 77 patients with NMOSD and 20 patients with MOGAD were reported in the COViMS Registry. Most patients with NMOSD were laboratory positive for SARS-CoV-2 and taking rituximab at the time of COVID-19 diagnosis. Most patients with NMOSD were not hospitalized (64.9% [95% CI: 53.2%-75.5%]), whereas 15.6% (95% CI: 8.3%-25.6%) were hospitalized only, 9.1% (95% CI: 3.7%-17.8%) were admitted to the ICU and/or ventilated, and 10.4% (95% CI: 4.6%-19.5%) died. In patients with NMOSD, having a comorbidity was the sole factor identified for poorer COVID-19 outcome (OR = 6.0, 95% CI: 1.79-19.98). Most patients with MOGAD were laboratory positive for SARS-CoV-2, and almost half were taking rituximab. Among patients with MOGAD, 75.0% were not hospitalized, and no deaths were recorded; no factors were different between those not hospitalized and those hospitalized, admitted to the ICU, or ventilated. DISCUSSION: Among the reported patients with NMOSD, a high mortality rate was observed, and the presence of comorbid conditions was associated with worse COVID-19 outcome. There were no deaths reported in the patients with MOGAD, although these observations are limited due to small sample size