Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Clinical Characteristics and Outcomes of 821 Older Patients With SARS-Cov-2 Infection Admitted to Acute Care Geriatric Wards

International audienceBackground: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19).Methods: We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged ≥ 70 years, with confirmed COVID-19, were enrolled.Results: Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥ 2 comorbidities; 29% lived in an institution; and the median (interquartile range) Activities of Daily Living Scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%) and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI], 27 to 33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR], 1.85; 95% CI, 1.30 to 2.63), ADL score < 4 (OR, 1.84; 95% CI, 1.25 to 2.70), asthenia (OR, 1.59; 95% CI, 1.08 to 2.32), quick Sequential Organ Failure Assessment score ≥ 2 (OR, 2.63; 95% CI, 1.64 to 4.22) and specific COVID-19 anomalies on chest computerized tomography (OR, 2.60; 95% CI, 1.07 to 6.46).Conclusions: This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate and asthenia can identify older patients at risk of unfavorable outcomes

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

International audienc

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old