COVID-19 in health-care workers: lessons from SARS and MERS epidemics and perspectives for chemoprophylaxis and vaccines.

Introduction: The world is now facing the COVID-19 pandemic. Experience with SARS-CoV and MERS-CoV, and early reports about SARS-CoV-2 infection suggest that health-care settings and health-care workers (HCWs) are vulnerable in the context of the emergence of a new coronavirus. Areas covered: To highlight the need for prophylactic strategies particularly for HCWs, we identified SARS-CoV, MERS-CoV, and SARS-CoV-2 outbreaks in health-care settings and the incidence of infections in HCWs by a search on MEDLINE and MEDxRIV (for SARS-Cov-2). To identify prophylactic strategies against, we conducted a search on MEDLINE and clinicaltrials.gov about studies involving SARS-CoV, MERS-CoV, and SARS-CoV-2. Expert opinion: HCWs account for a great part of SARS, MERS, and SARS-CoV-2 infections, they may also contribute to the spread of the disease, particularly in health-care settings, and contribute to nosocomial outbreaks. Some preventive strategies were evaluated in previous emerging coronavirus epidemics, particularly in MERS-CoV. For COVID-19 prevention, different chemoprophylaxis with drug repositioning and new agents are under evaluation, and different vaccine candidates entered clinical development, with clinical trials. HCWs are a crucial target population for pre-exposure and post-exposure prophylaxis.

Evaluation of Infliximab and Anti-infliximab LISA-TRACKER Immunoassays for the Therapeutic Drug Monitoring of SB2 Infliximab Biosimilar.

BACKGROUND: SB2, an infliximab (IFX) biosimilar to the reference infliximab (R.I.) product (Remicade), received approval in the European Union for all IFX indications. Many decision algorithms based on the measurement of IFX trough levels and antibodies to infliximab are being increasingly used to optimize IFX treatment. The aim of our study was to evaluate whether the biosimilar SB2 could be efficiently monitored using the LISA-TRACKER IFX and anti-IFX assays developed by Theradiag (Croissy Beaubourg, France). METHODS: Standard curves of R.I. and SB2 were compared, and then accuracy of the LISA-TRACKER IFX assay in detecting the spiked concentration of SB2 was measured. Levels of IFX from SB2 spiked samples and R.I. clinical samples were calculated. Intra-run and inter-run imprecision were also measured with SB2 spiked samples. The ability of polyclonal antibodies directed against R.I. to block the detection of SB2 using the LISA-TRACKER IFX assay and the capacity of SB2 to block the detection of anti-R.I. antibodies using the LISA-TRACKER anti-IFX assay were tested. RESULTS: Twelve patients treated with SB2 including 2 patients with SB2-specific antibodies were measured with the LISA-TRACKER anti-IFX assay. We demonstrated that the LISA-TRACKER assay is suitable for the quantification of SB2 in human serum samples. The percentage of recovery was between 82% and 113%. High intra-run and inter-run imprecisions were obtained with the LISA-TRACKER infliximab assay for the quantification of SB2 (SD ranged from 3.3% to 17.9%). The SB2-blocking capacity of R.I. polyclonal antibodies in spiked samples was demonstrated with inhibition between 80% and 97%. SB2 trough levels and anti-SB2 antibodies have also been confirmed in SB2-treated patients. CONCLUSIONS: LISA-TRACKER IFX and anti-IFX assays are suitable for the monitoring of patients treated with SB2.

Comparison of Point-of-Care and Classical Immunoassays for the Monitoring Infliximab and Antibodies Against Infliximab in IBD.

OBJECTIVE: The primary objective is to assess whether the POC assays to measure infliximab residual trough level in the serum of IBD patients were non-inferior to the ELISA techniques available on the market, and to determine which of them was the most robust. The second is to compare three different ELISA kits for monitoring anti-infliximab antibodies (ATI). METHODS: The assays were carried out on patients' sera using four ELISA kits from four different suppliers (three with a monoclonal antibody and one polyclonal) and two rapid techniques provided by BÜHLMANN (Quantum Blue®) and R-Biopharm (Ridaquick) for monitoring infliximab levels. ATI were measured by three ELISA sets (Grifols, Theradiag, and R-Biopharm) which have different positivity limits and different units. RESULTS: We measured infliximab residual level and ATI in the serum of 90 IBD patients (85 treated with infliximab and five with adalimumab). All of the infliximab assays were very well correlated when analyzed with Spearman nonparametric correlation (0.93 ≤ r ≤ 0.99), and the two POC assays were also excellently correlated (r = 0.98). The ATI monitoring kits revealed a correlation ranging from 0.73 to 0.96 when comparing positive and negative patients. When normalizing the quantitative values between the different ELISA tests (expressed arbitrarily by using multiples of the positivity limits defined by each supplier), the Spearman r coefficient ranged from 0.81 to 0.93. CONCLUSION: The available evidence allows us to conclude that all of the infliximab monitoring assays correlate well and may be used for IFX monitoring; albeit variations in measured IFX concentration among different assays remain present, these assays could be interchangeable. The ATI monitoring techniques are all capable of detecting ATI-positive patients, but because of the difference in the positivity limits and the measurement units, it is better to follow a patient rate with one definite kit.

Filgotinib for the treatment of Crohn's disease.

INTRODUCTION: Inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are widespread diseases (with an estimated 2.2 million Europeans affected), and even populations previously considered 'low risk' (such as Japan and India) are witnessing an increasing incidence. CD is a chronic, progressive immunologically driven disease, with an evolution characterized by succession of periods of progression and remission. New physiopathological pathways are continuously being discovered, the more we understand about how the disease appears and progresses, the more targets become available for the development of novel therapies. Areas covered: Filgotinib is one of these promising new therapies; this article discusses the currently available data. We used an exhaustive search of the PubMed database to corroborate information regarding its chemical characteristics, and the studies evaluating clinical efficacy and safety. Expert opinion: Up to now, the phase-II study evaluating Filgotinib yielded very promising results in moderate to severe CD patients, with good clinical response, mucosal healing, while having few and moderate adverse effects, both in anti-TNF naïve and resistant patients. Phase-III studies are still ongoing and will help decide whether Filgotinib will be a worthwhile drug in the treatment of CD and the best way to use it.

Role of astrocytes in thiamine deficiency.

Thiamine deficiency (TD) is the underlying cause of Wernicke's encephalopathy (WE), an acute neurological disorder characterized by structural damage to key periventricular structures in the brain. Increasing evidence suggests these focal histological lesions may be representative of a gliopathy in which astrocyte-related changes are a major feature of the disorder. These changes include a loss of the glutamate transporters GLT-1 and GLAST concomitant with elevated interstitial glutamate levels, lowered brain pH associated with increased lactate production, decreased levels of GFAP, reduction in the levels of glutamine synthetase, swelling, alterations in levels of aquaporin-4, and disruption of the blood-brain barrier. This review focusses on how these manifestations contribute to the pathophysiology of TD and possibly WE.