Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α.

OBJECTIVES: Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-ß and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. METHODS: We retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-ß and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns. RESULTS: Neutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity. CONCLUSION: The production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.

Hydroxychloroquine in systemic lupus erythematosus: overview of current knowledge.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ's effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

Immediate consequences and solutions used to maintain medical education during the COVID-19 pandemic for residents and medical students: a restricted review.

BACKGROUND: The COVID-19 outbreak has dramatically impacted medical education, both bedside and academic teaching had to be adapted to comply with the reorganisation of care and social distancing measures. OBJECTIVES: To overview the impact of the pandemic on medical education, including the pedagogical responses adopted and their assessment by medical students and residents. MATERIAL AND METHODS: This restricted systematic review was performed using Rayyan QCRI, to select observational or interventional articles and field experience reports assessing the impact of the COVID-19 pandemic on medical education for medical students and residents. Study design, study population, geographical origin, use of an educational tools (including softwares and social media), their type and assessment, were recorded. For studies evaluating a specific tool the Medical Education Research Study Quality Instrument (MERSQI) was used to assess study quality. RESULTS: The literature search identified 1480 references and 60 articles were selected. Most articles focused on residents (41/60; 69%), and half (30/60; 50%) involved surgical specialties. Online courses were the most frequently used pedagogical tool (52/60; 88%). Simulation tools were used more frequently in articles involving surgical specialties (15/29; 52%) compared with medical specialties (2/14; 12%) (p=0.01). Only four studies reported the assessment of pedagogical tools by medical students, their MERSQI scores ranged from 5.5/18 to 9.0/18. CONCLUSION: Medical education was highly impacted by the COVID-19 pandemic particularly in surgical specialties. Online courses were the most frequently attempted solution to cope with social distancing constraints. Medical students' assessment of pedagogical tools was mostly positive, but the methodological quality of those studies was limited.