Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

NSP5 (2)

ProteinS (2)

NSP3 (1)

NSP1 (1)


SARS-CoV-2 Proteins
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    Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia MESHD in COVID-19 MESHD

    Authors: Alexandra Tsitsiklis; Beth Shoshana Zha; Ashley Byrne; Catherine Devoe; Sophia Levan; Elze Rackaityte; Sara Sunshine; Eran Mick; Rajani Ghale; Alejandra Jauregui; Aartik Sarma; Norma Neff; Paula Hayakawa Serpa; Thomas J. Deiss; Amy Kistler; Sidney Carrillo; K. Mark Ansel; Aleksandra Leligdowicz; Stephanie Christenson; Norman Jones; Bing Wu; Spyros Darmanis; Michael M Matthay; Susan V Lynch; Joseph L. DeRisi; - COMET Consortium; Carolyn M. Hendrickson; Kristen N. Kangelaris; Matthew F. Krummel; Prescott G. Woodruff; David J. Earle; Oren Rosenberg; Carolyn S. Calfee; Charles R. Langelier

    doi:10.1101/2021.03.23.21253487 Date: 2021-03-26 Source: medRxiv

    Secondary bacterial infections MESHD, including ventilator associated pneumonia MESHD (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections MESHD. Critically ill MESHD patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD) face an elevated risk of VAP, although susceptibility varies widely. Because mechanisms underlying VAP MESHD predisposition remained unknown, we assessed lower respiratory tract host immune responses and microbiome dynamics in 36 patients, including 28 COVID-19 MESHD patients, 15 of whom developed VAP MESHD, and eight critically ill controls. We employed a combination of tracheal aspirate bulk and single cell RNA sequencing (scRNA-seq). Two days before VAP onset, a lower respiratory transcriptional signature of bacterial infection MESHD was observed, characterized by increased expression of neutrophil degranulation, toll-like receptor and cytokine signaling pathways. When assessed at an earlier time point following endotracheal intubation, more than two weeks prior to VAP onset, we observed a striking early impairment in antibacterial innate and adaptive immune signaling that markedly differed from COVID-19 MESHD patients who did not develop VAP MESHD. scRNA-seq further demonstrated suppressed immune signaling across monocytes/macrophages, neutrophils and T cells. While viral load did not differ at an early post-intubation timepoint, impaired SARS-CoV-2 MESHD clearance and persistent interferon signaling characterized the patients who later developed VAP MESHD. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients who developed VAP MESHD, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. Together, these findings demonstrate that COVID-19 MESHD patients who develop VAP MESHD have impaired antibacterial immune defense weeks before secondary infection onset.

    Antimicrobial susceptibility patterns of respiratory Gram-negative bacterial isolates from COVID-19 MESHD patients in Switzerland

    Authors: Sven N. Hobbie

    doi:10.1101/2021.03.10.21253079 Date: 2021-03-12 Source: medRxiv

    Background Bacterial superinfections associated with COVID-19 MESHD are common in ventilated ICU patients and impact morbidity and lethality. However, the contribution of antimicrobial resistance to the manifestation of bacterial infections MESHD in these patients has yet to be elucidated. Methods We collected 70 Gram-negative bacterial strains, isolated from the lower respiratory tract of ventilated COVID-19 MESHD patients in Zurich, Switzerland between March and May 2020. Species identification was performed using MALDI- TOF HGNC; antibiotic susceptibility profiles were determined by EUCAST disk diffusion and CLSI broth microdilution assays. Selected Pseudomonas aeruginosa isolates were analyzed by whole-genome sequencing. Results P. aeruginosa (46%) and Enterobacterales (36%) comprised the two largest etiologic groups. Drug resistance in P. aeruginosa isolates was high for piperacillin/tazobactam (65.6%), cefepime (56.3%), ceftazidime (46.9%) and meropenem (50.0%). Enterobacterales isolates showed slightly lower levels of resistance to piperacillin/tazobactam (32%), ceftriaxone (32%), and ceftazidime (36%). All P. aeruginosa isolates MESHD and 92% of Enterobacterales isolates were susceptible to aminoglycosides, with apramycin found to provide best-in-class coverage. Genotypic analysis of consecutive P. aeruginosa isolates in one patient revealed a frameshift mutation in the transcriptional regulator nalC that coincided with a phenotypic shift in susceptibility to {beta}-lactams and quinolones. Conclusions Considerable levels of antimicrobial resistance may have contributed to the manifestation of bacterial superinfections in ventilated COVID-19 MESHD patients, and may in some cases mandate consecutive adaptation of antibiotic therapy. High susceptibility to amikacin and apramycin suggests that aminoglycosides may remain an effective second-line treatment of ventilator-associated bacterial pneumonia MESHD, provided efficacious drug exposure in lungs can be achieved.

    Lower respiratory tract sampling via bronchoscopy in COVID-19 MESHD ARDS - A focus on microbiology, cellular morphology, cytology and management impact

    Authors: Sameer Bansal; Hariprasad Kalpakam; Ashwin Kumar; Amogha Varshaa; Anmol Thorbole; Ravindra M Mehta

    doi:10.1101/2021.02.22.21252201 Date: 2021-02-23 Source: medRxiv

    BackgroundLower respiratory tract (LRT) sampling via bronchoscopy has been done sparingly in COVID-19 MESHD ARDS due to the high aerosol risk for the health care workers (HCW). Valuable information can be gained by detailed evaluation of bronchoscopic LRT samples. MethodsLRT samples were obtained by bedside bronchoscopy performed in suspected or confirmed severe COVID-19 MESHD ARDS MESHD patients on mechanical ventilation. Only positive cases were included in the study. Microbiological, cellular and cytological studies including LRT COVID-19 MESHD RT-PCR were performed and analysed. Results100 samples were collected from 63 patients, 53 were males (84%). 43 patients (68%) had at least 1 comorbidity. 55% cases had secondary bacterial infection MESHD as demonstrated by positive culture. Most of these infections were due to multi-drug resistant organisms (94.5%). The most common organisms were Klebsiella pneumoniae MESHD and Acinetobacter baumanii in 56.3% and 14.5% cases respectively. Fungal superinfection was observed in 9 patients (14.3%). Bronchoscopy helped confirm COVID-19 MESHD diagnosis in 1 patient and helped rule out COVID-19 MESHD in 3 patients who were eventually excluded from the study. The median BAL fluid (BALF) WBC count was 953 (IQR; 400-2717), with mean neutrophil count 85.2% ({+/-}13.9), and mean lymphocyte count 14.8% ({+/-}13.9). Repeat sampling done in some patients showed a progressive increase in the total WBC count in BALF, an increase in neutrophil percentage, and a higher chance of isolating an organism on the culture (81% repeat procedures were culture positive). The rate of super-infection increased with longer duration of illness. Patients with superinfection also had an increased WBC count (1001 vs 400), and lower lymphocyte percentage (19% vs 12% - OR - 6.8 [95%CI -14.3 - 0.7]). Bronchoscopic LRT sampling contributed significantly to modifying antibiotic coverage and discontinuing steroids in 37% cases. ConclusionThis study describes a detailed analysis of bronchoscopic LRT sampling in critically ill COVID-19 MESHD patients. This provided important basic and applied information augmenting disease understanding and contributing to clinical management when there was scant information available in the pandemic.

    Clinical Characteristics of Severe COVID-19 MESHD in China: A Case Series and Meta-analysis

    Authors: Geling Teng; Hua Hu; Xia Wang; Junsheng Wang; Hongmei Zhang; Ying Chen

    doi:10.21203/ Date: 2021-01-29 Source: ResearchSquare

    Background: There have been inconsistent reports regarding the unique manifestations of severe coronavirus disease 2019 MESHD ( COVID-19 MESHD) occurring in China. This study analyzed the clinical manifestation of 13 severe COVID-19 MESHD cases at a single institution and compared the data to previously reported characteristics of severe COVID-19 MESHD in China. Methods: This retrospective case study included patients with severe COVID-19 MESHD who were admitted to the isolation ward of the Shandong Chest Hospital from January 2020 to February 2020. The clinical signs and symptoms, laboratory examination results, imaging features, treatment strategies, and patient prognoses were summarized. A database search was then conducted for studies published through December 2020 documenting characteristics of severe COVID-19 MESHD cases in China. The pooled results for severe COVID-19 MESHD patients in China were calculated by using the random-effects model.Results: A total of 4 severe and 9 critical patients were included from Shandong Chest Hospital. The average patient age was 55.3 (range 23-88) years, and 61.5% of patients were male. Chest computed tomography for all patients showed multiple lesions as ground-glass shadows in both lungs. All patients presented bacterial infection MESHD and various degrees of liver and myocardial injury MESHD. The treatment strategies for patients included antibiotics, immunoglobulin, and glucocorticoids, and mechanical ventilation was used in all patients for respiratory failure MESHD. Two patients died, and 11 recovered. In the pooled data for severe COVID-19 MESHD patients, the most common comorbidities were hypertension MESHD, diabetes mellitus MESHD, and coronary heart disease MESHD. The common signs in these patients were fever MESHD, cough MESHD, fatigue MESHD, chest tightness MESHD, and a leukocyte count > 10. Conclusions: Older males with hypertension MESHD, diabetes mellitus MESHD, and coronary heart disease MESHD may be at higher risk of developing severe COVID-19 MESHD. Patients should be assessed for concomitant bacterial infections MESHD. Cardiac and liver enzymes, fever MESHD, cough MESHD, fatigue MESHD, chest tightness MESHD, and leukocytosis MESHD should be monitored for signs of disease progression. 

    Fever MESHD without source as the first manifestation of SARS-CoV-2 infection MESHD in infants less than 90 days old.

    Authors: Daniel Blázquez-Gamero; Cristina Epalza; José Antonio Alonso Cadenas; Lourdes Calleja Gero; Cristina Calvo; Paula Rodríguez Molino; María Méndez; Mar Santos; Victoria Fumadó; María Fernanda Guzmán; Antoni Soriano-Arandes; Ana B. Jiménez; Maria Penin; Elvira Cobo-Vazquez; Marta Pareja León; Zulema Lobato; Miquel Serna; Rafael Delgado; Cinta Moraleda; Alfredo Tagarro

    doi:10.21203/ Date: 2021-01-28 Source: ResearchSquare

    Fever MESHD without source (FWS) in infants is a frequent cause of consultation at the emergency department and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection MESHD. This is a cross-sectional study of infants under 90 days of age with FWS MESHD and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 HGNCst to June 26th, 2020. Three hundred and thirty-three  children with COVID-19 MESHD were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia MESHD. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia MESHD, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the Pediatric Intensive Care Unit because of apnea MESHD episodes. No patients died. Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection MESHD. Standardized markers to rule out bacterial infections MESHD remain useful in this population, and the outcome is generally good.

    Pulmonary bacterial infections MESHD in patients hospitalized for COVID-19 MESHD: a retrospective observational study

    Authors: Maya HUSAIN; Simon Valayer; Nora Poey; Emilie Rondinaud; Camille d’Humières; Benoit Visseaux; Sylvie Lariven; François-Xavier Lescure; Laurène Deconinck

    doi:10.21203/ Date: 2021-01-27 Source: ResearchSquare

    Backround During the COVID-19 pandemic MESHD, antibiotics use was very common. However, bacterial co/secondary infections with coronaviruses remain largely unknown, especially outside of intensive care. The aim of this study was to investigate the pulmonary bacterial infections MESHD characteristics associated with COVID-19 MESHD in hospitalized patients.Methods A retrospective monocentric observational study was conducted in Bichat hospital in France, between February 26 and April 22, 2020. All patients hospitalized in standard wards with COVID-19 MESHD (positive nasopharyngeal PCR and/or typical aspect on CT scan) and diagnosed with a pulmonary bacterial infection MESHD (positive bacteriological samples) were included. Bacteriological and clinical data were collected from the microbiology laboratories and the patient's medical records.Results Twenty-three bacteriological samples from 22 patients were positive out of 2075 screened samples (1.1%) from 784 patients (2.8%). Bacterial infection MESHD occurred with a median of ten days after COVID-19 MESHD onset. Diagnosis of pulmonary bacterial infection MESHD was suspected on the increase of oxygen requirements (20/22), productive cough MESHD or modification of sputum (17/22), or fever MESHD (10/22). Positive samples included 13 sputum cultures, one Film Array® on sputum, one bronchoalveolar lavage, six blood cultures and two pneumococcal antigenuria MESHD. The most frequent bacteria were Pseudomonas aeruginosa (6/23), Staphylococcus aureus (5/23), Streptococcus pneumoniae (4/23), Enterococcus faecalis (3/23) and Klebsiella MESHD aerogenes (3/23). No Legionella antigenuria MESHD was positive. Four out of 496 nasopharyngeal PCR (0.8%) were positive for intracellular bacteria (two Bordetella pertussis MESHD and two Mycoplasma pneumonia MESHD).Conclusions Pulmonary bacterial secondary infections MESHD and co-infections MESHD with SARS-CoV-2 are uncommon. Antibiotic use should remain limited in the management of COVID-19 MESHD.

    Secondary Bacterial Infections and Antimicrobial Resistance in COVID-19 MESHD: Comparative Evaluation of Pre-Pandemic and Pandemic- Era HGNC, A Retrospective Single Center Study

    Authors: Mustafa Karataş; Melike Yaşar Duman; Alper Tünger; Feriha Çilli; Şöhret Aydemir; Volkan Ozenci

    doi:10.21203/ Date: 2021-01-27 Source: ResearchSquare

    Purpose: In this study, we aimed to evaluate the epidemiology and antimicrobial resistance (AMR) patterns of bacterial pathogens in COVID-19 MESHD patients and to compare the results with control groups from the pre-pandemic and pandemic era HGNC.Methods: Microbiological database records of all the COVID-19 MESHD diagnosed patients in the Ege University Hospital between March 15, 2020, and June 15, 2020, evaluated retrospectively. Patients who acquired secondary bacterial infections MESHD (SBIs) and bacterial co-infections MESHD were analyzed. Etiology and AMR data of the bacterial infections MESHD were collected. Results were also compared to control groups from pre-pandemic and pandemic era HGNC data.Results: In total, 4,859 positive culture results from 3,532 patients were analyzed. Fifty-two (3.59%) patients had 78 SBIs and 38 (2.62%) patients had 45 bacterial co-infections MESHD among 1,447 COVID-19 MESHD patients. 22/85 (25.88%) patients died who had bacterial infections MESHD. The respiratory culture-positive sample rate was 39.02% among all culture-positive samples in the COVID-19 MESHD group. There was a significant decrease in extended-spectrum beta-lactamase-producing Enterobacterales (8.94%) compared to samples from the pre-pandemic (20.76%) and pandemic era HGNC (20.74%) (p=0.001 for both comparisons). Interestingly, Acinetobacter baumannii was the main pathogen in the respiratory infections of COVID-19 MESHD patients (%9.76) and the rate was significantly higher than pre-pandemic (3.49%, p<0.002) and pandemic era HGNC control groups (3.11%, p<0.001).Conclusion: Due to the low frequency of SBIs reported during the ongoing pandemic, a more careful and targeted antimicrobial prescription should be taken. While patients with COVID-19 MESHD had lower levels of ESBL producing Enterobacterales, the frequency of MDR A. baumannii is higher.  

    Two original observations concerning bacterial infections MESHD in COVID-19 MESHD patients hospitalized in intensive care units during the first wave of the epidemic in France

    Authors: Camille d'Humieres; Juliette Patrier; Brice Lortat-Jacob; Alexy Tran-dinh; Lotfi Chemali; Naouale Maataoui; Emilie Rondinaud; Etienne Ruppe; Charles Burdet; Stephane Ruckly; Philippe Montravers; Jean-Francois Timsit; Laurence Armand-Lefevre

    doi:10.1101/2021.01.22.21250287 Date: 2021-01-26 Source: medRxiv

    Among 197 COVID-19 MESHD patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection MESHD, with pneumonia MESHD (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.

    Risk Factors for Bacterial Infections in Patients With Moderate to Severe COVID-19 MESHD: a Case Control Study

    Authors: Nosheen Nasir; Fazal ur Rehman; Syed Furrukh Omair

    doi:10.21203/ Date: 2021-01-25 Source: ResearchSquare

    ObjectiveBacterial infections are known to complicate respiratory viral infections MESHD and are associated with adverse outcomes in COVID-19 MESHD patients. A case control study was conducted to determine risk factors for bacterial infections MESHD where cases were defined as moderate to severe/critical COVID-19 MESHD patients with bacterial infection MESHD and those without were included as controls. Logistic regression analysis was performed.  ResultsOut of a total of 50 cases and 50 controls, greater proportion of cases had severe or critical disease MESHD at presentation as compared to control i.e 80% vs 30% (p<0.001). Hospital acquired pneumonia MESHD (72%) and Gram negative organisms (82%) were predominant. Overall antibiotic utilization was 82% and was 64% in patients who had no evidence of bacterial infection MESHD. The median length of stay was significantly longer among cases compared to controls (12.5 versus 7.5 days) (p=0.001). The overall mortality was 30%, with comparatively higher proportion of deaths among cases (42% versus 18%) (p=0.009). Severe or critical COVID-19 MESHD at presentation (AOR: 4.42 times; 95% CI; 1.63-11.9) and use of steroids (AOR: 4.60; 95% CI 1.24-17.05) were independently associated with risk of bacterial infections MESHD. These findings have implications for antibiotic stewardship as antibiotics can be reserved for those at higher risk for bacterial superinfections. 

    Synthetic hydrogel nanoparticles for sepsis therapy MESHD

    Authors: Kenneth Shea; Hiroyuki Koide; Anna Okishima; Yu Hoshino; Yuri Kamon; Keiichi Yoshimatsu; Kazuhiro Saito; Ikumi Yamauchi; Saki Ariizumi; Naoto Oku; Tomohiro Asai; Yuqi Zhou; Ting-Hui Xiao; Keisuke Goda Keisuke Goda

    doi:10.21203/ Date: 2021-01-19 Source: ResearchSquare

    Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection MESHD, COVID-19 MESHD), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis MESHD. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis MESHD. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis MESHD. The highly optimized HNP has high capacity and long-term circulation capability for the selective sequestration and neutralization of histones. Intravenous injection of the HNP protected mice against a lethal dose of histones through the inhibition of platelet migration into the lungs. In vivo administration in murine sepsis MESHD model mice resulted in near complete survival. These results establish the potential for synthetic, nonbiological polymer hydrogel sequestrants as a new intervention strategy for sepsis MESHD therapy and adds to our understanding of the importance of histones to this condition.  

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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