Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and ...whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes, accumulation of HLA-DRLow classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101−CXCR4+/− neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.
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•Patients with severe COVID-19 accumulate HLA-DRLow monocytes and immature neutrophils in blood/lungs•Calprotectin level positively correlates with neutrophil count and disease severity•Loss of non-classical monocytes could identify high risk of severe COVID-19
An analysis of patients with severe COVID-19 reveals immature neutrophil and non-classical monocyte pools, with levels of the protein calprotectin linked to disease severity.
•Isolated loss of smell without nasal obstruction is an early red-flag of COVID-19.•These patients should adopt all the preventive measures and a lockdown.•Olfactory/gustative dysfunction had high ...predictive value to identify COVID-19.•Olfactory/gustative dysfunction had high specificity to identify COVID-19.•Self-reported loss of smell, among other symptoms, could help to screen COVID-19.
To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period.
Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19.
i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%)).
Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts.
The role of defects in the fracture of an Al–Si–Mg cast alloy Francis, John A.; Cantin, G.M. Delphine
Materials science & engineering. A, Structural materials : properties, microstructure and processing,
10/2005, Letnik:
407, Številka:
1
Journal Article
Recenzirano
A study of the tensile behaviour of test coupons that were extracted from cast plates of D357 aluminium is described. The effects of specimen thickness, heat treatment, structural integrity and hot ...isostatic pressing (HIP) were investigated. Chevron marks were found on the fracture surfaces of the specimens that failed under plane strain conditions. In most cases, structural defects, such as shrinkage pores and oxide films, were found at the initiation sites for fracture. It is shown that the structural defects that were found at the origin of the chevron patterns are large enough to explain the fractures, and that the tensile failure of cast Al–7Si–Mg alloys can be explained in terms of the principles of fracture mechanics. The influence of structural defects on the elongation to fracture is discussed, together with some implications for quality control programs involving cast Al–7Si–Mg components.
Acute attacks of hereditary angioedema are characterized by recurrent localized edema. These attacks can be life threatening and are associated with substantial morbidity and mortality.
To determine ...factors associated with hospital admission of patients with an acute attack of hereditary angioedema presenting at the emergency department.
This was a multicenter prospective observational study of consecutive patients (January 2011 through December 2013) experiencing an acute hereditary angioedema attack and presenting at the emergency department at 1 of 4 French reference centers for bradykinin-mediated angioedema. Attacks requiring hospital admission were compared with those not requiring admission.
Of 57 attacks in 29 patients, 17 (30%) led to hospital admission. In multivariate analysis, laryngeal and facial involvements were associated with hospital admission (odds ratio 18.6, 95% confidence interval 3.9-88; odds ratio 7.7, 95% confidence interval 1.4-43.4, respectively). Self-injection of icatibant at home was associated with non-admission (odds ratio 0.06, 95% confidence interval 0.01-0.61). The course was favorable in all 57 cases. No upper airway management was required.
Most patients attended the emergency department because they were running out of medication and did not know that emergency treatment could be self-administered. Risk factors associated with hospital admission were laryngeal and facial involvement, whereas self-injection of icatibant was associated with a return home.
The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the ...clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
Introduction: Cocaine body packing, the internal concealment of cocaine for transportation between countries, may expose to life-threatening intoxications. No data is currently available on the ...pharmacokinetics of cocaine and its metabolites when a packet rupture occurs in a body packer. Case report: We report the first pharmacokinetic data associated with a severe cocaine intoxication in a body packer, resulting in cardiac arrest. Massive concentrations of cocaine (observed maximal concentration: 1.66 mg/L, 1 hour after the cardiac arrest) were measured in plasma up to about 15 hours, suggesting a prolonged absorption due to a slow-release in the gastrointestinal tract despite surgical extraction of the packets. Apparent cocaine elimination half-life was 7.6 hours. Conclusion: A prolonged apparent cocaine elimination half-life has been observed. Further pharmacokinetic studies are needed to understand better the pathophysiology of acute cocaine intoxication in body packers.
We 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 ~ 80% of cases.
We 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.
No 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 = 1.1 × 10
) 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 = 3.7095%CI 1.3-8.2, P = 2.1 × 10
). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.6595%CI 2.1-2635.4, P = 3.4 × 10
), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.409%CI 2.3-8.4, P = 7.7 × 10
). 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 = 1.68 × 10
).
Rare 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.
Chest CT is the reference test for assessing pulmonary injury in suspected or diagnosed COVID-19 with signs of clinical severity. This study aimed to evaluate the association of a lung ...ultrasonography score and unfavorable clinical evolution at 28 days. The eChoVid is a multicentric study based on routinely collected data that was conducted in 8 emergency units in France; patients were included between March 19, 2020 and April 28, 2020 and underwent lung ultrasonography, a short clinical assessment by 2 emergency physicians blinded to each other's assessment, and chest CT. Lung ultrasonography consisted of scoring lesions from 0 to 3 in 8 chest zones, thus defining a global score (GS) of severity from 0 to 24. The primary outcome was the association of lung damage severity as assessed by the GS at day 0 and patient status at 28 days. Secondary outcomes were comparing the performance between GS and CT scan and the performance between a new trainee physician and an ultrasonography expert in scores. For the 328 patients analyzed, the GS showed good performance in predicting clinical worsening at 28 days (area under the receiver operating characteristic curve AUC 0.83, sensitivity 84.2%, specificity 76.4%). The GS showed good performance in predicting the CT severity assessment (AUC 0.84, sensitivity 77.2%, specificity 83.7%). A lung ultrasonography GS is a simple tool that can be used in the emergency department to predict unfavorable assessment at 28 days in patients with COVID-19.
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