Asthma Associated Cytokines Regulate the Expression of SARS-CoV-2 Receptor ACE2 in the Lung Tissue of Asthmatic Patients

It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.

Effect of the SARS-CoV-2 pandemic on the control and severity of pediatric asthma

Background: The novel disease caused by the new coronavirus SARS-CoV-2 has caused an unprecedented global pandemic. Care providers of asthmatic children are increasingly con-cerned; as viral infections are one of the primary triggers of asthma flare-up. However, the effect of SARS-CoV-2 as well as the generated worldwide lockdown on asthmatic children is unknown.Objective: The aim of this study was to analyze the effects of pandemic SARS-CoV-2 in pediat-ric asthma control.Material and Methods: A retrospective, open, transversal study was performed at five tertiary hospitals. Recruited patients were aged <18 years and had physician-diagnosed asthma. Information regarding the 2019 and 2020 seasons were provided.Results: Data were collected from 107 children (age range: 3–18 years, mean age: 12 years). Well-controlled asthma was observed in 58 (54.2%) patients in 2020 versus 30 (28%) in 2019, and 15 (14%) patients had poorly controlled asthma in 2020 versus 28 (26.2%) in 2019. In 2020, a decrease in exacerbations caused by allergies to pollen, dust mites, molds, and through other causes not related to SARS-CoV-2 infection was observed. An increase in exacerbations was observed due to animal dander, stress, physical exercise, and SARS-CoV-2 infection. Children had a reduced need for asthma-controlling medication, made fewer visits to healthcare pro-viders and had lesser need of treatment with oral corticosteroids if compared with the same season of 2019.Conclusion: Pediatric asthma control improved, the need for controller medication declined, and fewer visits to healthcare providers were made during the pandemic if compared with the 2019 season.

Guanidinoacetate–creatine in secondary progressive multiple sclerosis: a case report

Acute secondary progressive multiple sclerosis (SPMS) is characterized by escalating neurological disability, with limited disease-modifying therapeutic options. A 48-year-old woman with acute SPMS being treated with interferon beta-1a and oral corticosteroids presented as a clinical outpatient with no disease-modifying effects after treatment. A decision was made to treat her with a combination of guanidinoacetate and creatine for 21 days. She had made clinical progress at follow-up, with the intensity of fatigue dropping from severe to mild. Magnetic resonance spectroscopy revealed increased brain choline, creatine, N-acetylaspartate, and glutathione. Patients with SPMS may benefit from guanidinoacetate–creatine treatment in terms of patient- and clinician-reported outcomes; this requires additional study.

Oral Manifestations of Immune Thrombocytopenic Purpura

Introduction: Hemorrhagic lesions of the oral mucosa are the most common clinical manifestations of Immune thrombocytopenic purpura (ITP). Case Report: A 41-year-old female patient consulted the oral surgery department of the dental consultation and treatment center in Rabat for spontaneous gingivorrhagia. Clinical examination and further examination showed severe thrombocytopenia associated with an anemic syndrome. The diagnosis of ITP was made. Treatment was based on oral corticosteroids and immunoglobulin in the hospital. Conclusion: These manifestations sometimes lead the patient to consult his dental surgeon in the first intention, hence the need to make the diagnosis based on a thorough global examination and to refer the patient to an adapted structure.

Efficacy And Safety of Canakinumab As A Second-Line Biologic After Tocilizumab Treatment Failure in Children With Systemic Juvenile Idiopathic Arthritis: A Single-Center Cohort Study Using Routinely Collected Health Data

Background: A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (DMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.Methods: Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the pediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS‑71 =0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from outpatient medical records.Results: During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at canakinumab initiation was 8.2 (interquartile range 4.0; 12.9) years, and median sJIA duration was 1.8 (0.8; 5.8) years; 37 (80%) patients received at least one non-biologic DMARD (oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (282; 404) days. During the follow-up, canakinumab was discontinued in one patient (due to tuberculosis detection) and the dose was reduced or the injection interval increased in four (9%) patients. In total, 27 (60%) patients continued to receive at least one non-biologic DMARD. Improvement according to the ACR30 criteria was achieved in 43 patients (96%; 95% confidence interval, 85–99), inactive disease in 42 (93%; 82–98), and clinical remission in 37 (82%; 69‑91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 adverse events (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.Conclusions: Short-term (about 12 months) canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA. Trial registration: CACZ885G2301E1 (G2301; NCT00891046 registered on April 29, 2009) and CACZ885G2306 (G2306; NCT02296424 registered on November 20, 2014).

Monitoring therapy in anterior necrotizing scleritis with inflammation with anterior segment optical coherence tomography

Introduction Early diagnosis and initiation of immunosuppression can prevent the necessity of surgical intervention in necrotizing scleritis with inflammation and lowers the risk of perforation and loss of vision. However, clinical signs for early diagnosis and methods for monitoring response to immunosuppressive therapy are missing. Methods Here, we present a case of necrotizing scleritis with inflammation where avascular plaques precede scleral defects. We use slit lamp imaging and anterior segment optical coherence tomography to evaluate evolution lesions depth and impact on scleral structure. Results The patient presented 5 months after detection of avascular plaques with a new scleral ulcer of the left eye. After 3-day-administration of i.v. corticosteroids anterior segment optical coherence tomography showed progressive scleral thickening. The patient was therefore spared surgical intervention and discharged resulting in complete remission under decreasing doses of oral corticosteroids. Conclusions Avascular plaques can precede necrotizing scleritis with inflammation by several months and may therefore qualify as early clinical signs. Anterior segment optical coherence tomography enables objective evaluation of scleral structure for making rational decisions about surgical intervention.