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

Background: 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. Methods: 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. Results: 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 × 10−4) 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 = 2.1 × 10−4). 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 = 3.4 × 10−3), 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 = 7.7 × 10−8). 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 = 1.68 × 10−5). Conclusions: 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

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Identification and overcome of limitations of weathered oil hydrocarbons bioremediation by an adapted Bacillus sorensis strain

Because of the high production of oil and gas in Qatar, the likelihood of oil spill occurrence is most probably susceptible to happen. Contaminated soil treatment is very expensive. Cost effective mechanisms are investigated to treat this threatening issue. For that reason, bioremediation and biotechnology tools are introduced to help accelerate and remove the pollution caused by the contamination process. This paper demonstrated the importance of optimising the treatment conditions to the indigenous bacterial strain to obtain the highest biodegradation efficiency rates. The usage of biopile system technology was used with biostimulation and bioaugmentation processes. The indigenous Bacillus sonorensis (B. sonorensis) D1 bacterium played a crucial role in the biodegradation process when introduced to optimized conditions; carbon/nitrogen/phosphorus (C/N/P) (100/10/1), temperature (37 °C), surfactant tween 80 (0.12% (v/w)), and moisture (10%). Gas chromatography (mass spectrometry/flame ionization detector) (GC- (MS/FID)), Fourier transform infrared (FTIR), and colony-forming unit (CFU) analyses were performed. The diesel range organics (DRO) and polycyclic aromatic hydrocarbons (PAH) removal (%) of the weathered oil contaminated soil reached, after 160 days, 39.2% and 32.4% simultaneously when ammonium nitrate was used as a nitrogen source. Whereas urea inhibited the oil degradation process and caused the pH to rise to 9.55.The authors acknowledge the staff of the Environmental StudyCenter, Qatar University, especially Mrs Noora M. Al-Shamary and MrMazen Abu Asali, for providing support in GC analysis. We also thankthe staff of the Central Laboratories Unit, of Qatar University especiallyMr Ahmed Ali Easa and Ms Muneera Al-Qahtani for providing sup-port in the FTIR analysis. This work was supported by Qatar UniversityGrants [QUST-CAS-FALL-15/16-15:QUST-2-CAS-2017-14].Scopu

Isolation, differentiation and biodiversity of ureolytic bacteria of Qatari soil and their potential in microbially induced calcite precipitation (MICP) for soil stabilization

Biomineralization plays a key role in modifying the geological properties of soil, thereby stabilizing it against wind erosion, especially in areas characterized by harsh weather and harsh soil (calcareous and arid); i.e. Arabic Gulf region. Among soil microorganisms, ureolytic bacteria are capable of modifying soil characteristics and thus, inducing biomineralization. This research investigated the occurrence and diversity of ureolytic bacteria in Qatari soils, specifically to study their acquired potential to adapt to harsh conditions exhibiting ureolytic activity. Soil samples were collected from various locations in Qatar and were used to isolate the indigenous ureolytic bacteria. It was noticed that most of the ureolytic bacteria in Qatari soil belong to the genus Bacillus mainly Bacillus cereus. Identification and differentiation of 18 ureolytic isolates were performed using MALDI-TOF MS techniques while ribotyping (16S rRNA) molecular technique was used mainly for 6 selected strains. This study not only shows the diversity of species of ureolytic bacteria in Qatari soil but also shows the diversity in their protein profiles, which confirms that bacteria have adapted well to the harsh environment. In addition, the strains were evaluated based on a newly modified screening method in this work; i.e. production of arbitrary urease activity (AUA). Thus, the strains showing the highest AUA, exhibited the highest capability to produce urease enzymes induced by urea. Analysis of calcium carbonate precipitation utilizing SEM-EDX showed that the ureolytic bacteria also play a significant role in the precipitation of minerals such as CaCO3, in the presence of urea in soil. Therefore, this research showed a high occurrence of indigenous Bacillus bacteria in Qatari soil that can perform biomineralization and thus can be helpful, if properly stimulated, in enhancing soil stabilization, and for other local applications as well, since they are adapted to these soil and weather conditions.This work was made possible by an NPRP 819292766, a grant from the Qatar National Research Fund (a member of the Qatar Foundation).Scopu

Attribute based content security and caching in information centric IoT

Information-centric networking (ICN) is a Future Internet paradigm which uses named information (data objects) instead of host-based end-to-end communications. In-network caching is a key pillar of ICN. Basically, data objects are cached in ICN routers and retrieved from these network elements upon availability when they are requested. It is a particularly promising networking approach due to the expected benefits of data dissemination efficiency, reduced delay and improved robustness for challenging communication scenarios in IoT domain. From the security perspective, ICN concentrates on securing data objects instead of ensuring the security of end-to-end communication link. However, it inherently involves the security challenge of access control for content. Thus, an efficient access control mechanism is crucial to provide secure information dissemination. In this work, we investigate Attribute Based Encryption (ABE) as an access control apparatus for information centric IoT. Moreover, we elaborate on how such a system performs for different parameter settings such as different numbers of attributes and file sizes

High Levels and Safety of Oseltamivir Carboxylate Plasma Concentrations after Nasogastric Administration in Critically Ill Children in a Pediatric Intensive Care Unit▿

During the 2009 H1N1 influenza pandemics, the concentrations of oseltamivir (O) and its active metabolite (oseltamivir carboxylate [OC]) were determined in 11 children (1 month to 16 years of age) admitted to intensive care units for presumed severe H1N1 infection. They received oseltamivir phosphate (OP) nasogastrically at doses between 1.5 and 6.8 mg/kg of body weight. High OC concentrations were found, with a mean level of 678 ± 535 μg/liter. The mean OP concentration was 27 ± 52 μg/liter. No marked side effect was reported

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2–Related Multisystem Inflammatory Syndrome in Children With Shock

NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5–11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35–45%), 261 ng/mL (131–390 ng/mL), and 3.2 mmol/L (2–4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5–28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814–11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987–192,499 pg/mL]), von Willebrand factor antigen (344% [288–378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472–1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2–related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms