Extreme 15N Depletion in Seagrasses

Seagrass beds form an important part of the coastal ecosystem in many parts of the world but are very sensitive to anthropogenic nutrient increases. In the last decades, stable isotopes have been used as tracers of anthropogenic nutrient sources and to distinguish these impacts from natural environmental change, as well as in the identification of food sources in isotopic food web reconstruction. Thus, it is important to establish the extent of natural variations on the stable isotope composition of seagrass, validating their ability to act as both tracers�of nutrients and food sources. Around the world, depending on the seagrass species and ecosystem, values of seagrass N normally vary from 0 to 8 ? ?15N. In this study, highly unusual seagrass N isotope values were observed on the east coast of Qatar, with significant spatial variation over a scale of a few metres, and with ?15N values ranging from +2.95 to ?12.39 ? within a single bay during March 2012. This pattern of variation was consistent over a period of a year although there was a seasonal effect on the seagrass ?15N values. Seagrass, water column and sediment nutrient profiles were not correlated with seagrass ?15N values and neither were longer-term indicators of nutrient limitation such as seagrass biomass and height. Sediment ?15N values were correlated with Halodule uninervis ?15N values and this, together with the small spatial scale of variation, suggest that localised sediment processes may be responsible for the extreme isotopic values. Consistent differences in sediment to plant 15N discrimination between seagrass species also suggest that species-specific nutrient uptake mechanisms contribute to the observed ?15N values. This study reports some of the most extreme, negative ?15N values ever noted for seagrass (as low as ?12.4 ?) and some of the most highly spatially variable (values varied over 15.4 ? in a relatively small area of only 655�ha). These results are widely relevant, as they demonstrate the need for adequate spatial and temporal sampling when working with N stable isotopes to identify food sources in food web studies or as tracers of anthropogenic nutrients.Scopu

Methylmercury, Trace Metals, Organotins and Their Effects on the Qatari Mangrove Shrimp, Palaemon khori

The Qatari mangroves of Al-Khor are being increasingly exposed to a wide variety of anthropogenic pollutants due to land reclamation and urban expansion. In this study, we evaluated the lethal and genotoxic effects of methylmercury, trace metals, and organotins, assessing mortality and aneuploidy levels (abnormal number of chromosomes) in the endemic shrimp Palaemon khori under laboratory conditions. In the experimental design, two different concentrations were used for each family of contaminant (single or combined): an environmental concentration equivalent to the maximum value reported in the environment and a value ten times higher, for a period of eight weeks. Survival decreased significantly when pollutants were administrated in combination, even at environmental concentrations (as shown by Cox proportional hazards ratios): similar levels of mortality would be reached by individual type of pollutants only at ten times the environmental concentration. This critical result, under controlled lab conditions, highlights the importance of monitoring mixtures of contaminant types over single ones in the marine environment. Aneuploidy was reported in all treatments and control ranging from 5% to 19% at week four and from 7% to 21% at week eight. All treatments presented significantly higher aneuploidy levels when compared to the control. However, no significant difference was observed between the two time periods, even though 30% of the treatments could not be assessed at week eight, as not enough animals were still alive. In conclusion, the use of endemic species should be considered a valuable tool to determine local perturbations, representing a regional bioindicator of multiple environmental stressors from the initial stages of contamination

Faunal mediated carbon export from mangroves in an arid area

The outwelling paradigm argues that mangrove and saltmarsh wetlands export much excess production to downstream marine systems. However, outwelling is difficult to quantify and currently 40–50% of fixed carbon is unaccounted for. Some carbon is thought outwelled through mobile fauna, including fish, which visit and feed on mangrove produce during tidal inundation or early life stages before moving offshore, yet this pathway for carbon outwelling has never been quantified. We studied faunal carbon outwelling in three arid mangroves, where sharp isotopic gradients across the boundary between mangroves and down-stream systems permitted spatial differentiation of source of carbon in animal tissue. Stable isotope analysis (C, N, S) revealed 22–56% of the tissue of tidally migrating fauna was mangrove derived. Estimated consumption rates showed that 1.4% (38 kg C ha−1 yr−1) of annual mangrove litter production was directly consumed by migratory fauna, with <1% potentially exported. We predict that the amount of faunally-outwelled carbon is likely to be highly correlated with biomass of migratory fauna. While this may vary globally, the measured migratory fauna biomass in these arid mangroves was within the range of observations for mangroves across diverse biogeographic ranges and environmental settings. Hence, this study provides a generalized prediction of the relatively weak contribution of faunal migration to carbon outwelling from mangroves and the current proposition, that the unaccounted-for 40–50% of mangrove C is exported as dissolved inorganic carbon, remains plausible.Qatar National Research Foundation, National Priorities Research Programme research grant: NPRP 7 - 1302 - 1 - 24

Inter-Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes

The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015–2017) and its implications on disease severity. A total of 90 nasal samples positive for the pH1N1 virus were deep-sequenced and analyzed to detect low-frequency variants (LFVs) and haplotypes. Parallel evolution of LFVs was seen in the hemagglutinin (HA) gene across three scales: among patients (33%), across years (22%), and at global scale. Remarkably, investigating the emergence of LFVs at the consensus level demonstrated that within-host virus evolution recapitulates evolutionary dynamics seen at the global scale. Analysis of virus diversity at the HA haplotype level revealed the clustering of low-frequency haplotypes from early 2015 with dominant strains of 2016, indicating rapid haplotype evolution. Haplotype sharing was also noticed in all years, strongly suggesting haplotype transmission among patients infected during a specific influenza season. Finally, more than half of patients with severe symptoms harbored a larger number of haplotypes, mostly in patients under the age of five. Therefore, patient age, haplotype diversity, and the presence of certain LFVs should be considered when interpreting illness severity. In addition to its importance in understanding virus evolution, sub-consensus virus diversity together with whole genome sequencing is essential to explain variabilities in clinical outcomes that cannot be explained by either analysis alone

Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study

Background Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. Methods and findings This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. Conclusion In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings.Scopu

Darunavir-Cobicistat versus Lopinavir-Ritonavir for COVID-19 Pneumonia: Qatar's Experience

Background: Coronavirus Disease 2019 (COVID-19) was first discovered in China and resulted in a pandemic crisis. 1,2 Many agents were investigated with inconclusive outcomes. 3 This study was conducted to compare the efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in the treatment of patients with COVID-19. Methods: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in COVID-19 facilities in Qatar. Patients were included if they had pneumonia and received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatment. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Data were analyzed descriptively and inferential statistics were applied at alpha level of 0.05. Results: A total of 400 patients' medical records were analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. The majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (SD 4.89). Patients who received lopinavir-ritonavir had a significantly faster time to the primary composite endpoint of clinical improvement and/or virological clearance than patients who received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], p = 0.011) [Figure 1]. Patients who received lopinavir-ritonavir had a significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), p = 0.000), and slower time to virological clearance than those who received darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), p = 0.035) [Figure 2]. No significant difference in adverse events incidence or severity was observed. Conclusion: In patients with COVID-19, early treatment with lopinavir-ritonavir was associated with faster time to reach the primary composite endpoint of clinical improvement and/or virological clearance than treatment with darunavir-cobicistat. Future trials are warranted to confirm these findings.qscienc

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial

Background: The global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes. Methods: In this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05. Results: Out 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39–7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy. Conclusion: In patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients’ subgroups characteristics that might benefit from administered therapy. Clinical Trial Registration: Trial registration at ClinicalTrials.gov, identifier: NCT04643678.This study was funded by the Medical Research Center at Hamad Medical Corporation, Qatar (MRC-01-20-1095)

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients. 2022, The Author(s).The authors would like to thank all the patients, volunteers, and the healthcare co-workers from Allergy and Immunology Section-HMC, and Dr. Mohamed G.H. Mohamedali, Mr. Hassen Maatoug, and Mr. Ahmed Soliman from Hezm Mebairek General Hospital-HMC for developing disposable racks for samples transportation, tubes labeling, blood collection, and handling. We thank the support provided by Qatar University Biomedical Research Centre, Biosafety Level 3, and Associate Professor Hadi M. Yassine (M.Sc., Ph.D.). We also acknowledge the help of the Anti-Doping Lab-Qatar (ADLQ) and Qatar Red Crescent (QRC) for recruiting control samples. This work was supported by a grant fund from Hamad Medical Corporation (fund number MRC-05-003) and core funding from Qatar Biomedical Research Institute (QBRI).Scopu

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality