Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5–11.8) vs 3.4 years (IQR 0.4–9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5–8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Long term monitoring of jaguars in the Cockscomb Basin Wildlife Sanctuary, Belize; Implications for camera trap studies of carnivores

<div><p>In this study, we estimate life history parameters and abundance for a protected jaguar population using camera-trap data from a 14-year monitoring program (2002–2015) in Belize, Central America. We investigated the dynamics of this jaguar population using 3,075 detection events of 105 individual adult jaguars. Using robust design open population models, we estimated apparent survival and temporary emigration and investigated individual heterogeneity in detection rates across years. Survival probability was high and constant among the years for both sexes (φ = 0.78), and the maximum (conservative) age recorded was 14 years. Temporary emigration rate for the population was random, but constant through time at 0.20 per year. Detection probability varied between sexes, and among years and individuals. Heterogeneity in detection took the form of a dichotomy for males: those with consistently high detection rates, and those with low, sporadic detection rates, suggesting a relatively stable population of ‘residents’ consistently present and a fluctuating layer of ‘transients’. Female detection was always low and sporadic. On average, twice as many males than females were detected per survey, and individual detection rates were significantly higher for males. We attribute sex-based differences in detection to biases resulting from social variation in trail-walking behaviour. The number of individual females detected increased when the survey period was extended from 3 months to a full year. Due to the low detection rates of females and the variable ‘transient’ male subpopulation, annual abundance estimates based on 3-month surveys had low precision. To estimate survival and monitor population changes in elusive, wide-ranging, low-density species, we recommend repeated surveys over multiple years; and suggest that continuous monitoring over multiple years yields even further insight into population dynamics of elusive predator populations.</p></div

Relevance of coronavirus viroporins and PDZ-binding-motifs in virus replication and virulence

Trabajo presentado en el 37th Annual Meeting American Society for Virology Symposia, celebrado en Maryland (Estados Unidos), del 14 al 18 de julio de 2018Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, SARS-CoV encodes three: proteins 3a, E and 8a. Additionally, 3a and E proteins have a PDZ-binding motif (PBM), which may bind over 400 cellular proteins containing a PDZ domain, making them relevant for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that both the full-length E and 3a proteins were required for optimum SARS-CoV replication and virulence whereas viroporin 8a had a minor impact on these activities. However, IC and PBM activities of E, but not 3a protein, were necessary for virulence in mice. Interdependence between E and 3a was identified. A virus missing both proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability, indicating functional redundancy between the PBMs of these proteins. Given the relevance of SARS-CoV PBMs, the presence of these motifs was studied in other CoVs. MERSCoV, another highly pathogenic human CoV, includes a PBM in both E and 5 proteins. The interaction between the 256 known human PDZ domains and the PBMs of SARS-CoV and MERS-CoV was studied using a specific yeast-two-hybrid platform. More than 20 cellular proteins mostly involved in virus-cell and cell-cell interaction were identified. Some of these proteins are involved in immune response or in the infectivity of other viruses. Collectively, these results demonstrate redundant roles for the IC and PBMs for optimal virus replication and pathogenesis suggesting that they are potential targets for antiviral therap

Jaguar survival, detection, immigration and emigration probabilities for the jaguar capture-recapture camera-trap data from CBWS, 2002–2015 (years 2009–2010 missing).

<p>Jaguar survival, detection, immigration and emigration probabilities for the jaguar capture-recapture camera-trap data from CBWS, 2002–2015 (years 2009–2010 missing).</p

Model selection for capture-recapture camera-trap data for jaguars, using robust design population models, CBWS 2002–2015 (years 2009–2010 missing).

<p>Model selection for capture-recapture camera-trap data for jaguars, using robust design population models, CBWS 2002–2015 (years 2009–2010 missing).</p