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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (18)

ProteinN (5)

ProteinE (4)

NSP5 (3)

ComplexRdRp (3)


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    Invasive airway "Intubation" in COVID-19 MESHD patients: statistics, causes and recommendations

    Authors: Mostafa Mohammadi; Alireza Khafaee Pour Khamseh; Hesam Aldin Varpaei

    doi:10.1101/2021.04.08.21254439 Date: 2021-04-11 Source: medRxiv

    Background: Severe COVID-19 MESHD disease could induce acute respiratory distress which is characterized by tachypnea MESHD, hypoxia MESHD, and dyspnea MESHD. Intubation and mechanical ventilation are a strategic treatment of COVID-19 MESHD distress or hypoxia MESHD. Methods: We searched PubMed, Embase, and Scopus databases through April 1, 2021, to identify relevant randomized control trials, observational studies, and case series. Results: 24 studies were included in this review. Studies were conducted in the USA, China, Spain, South Korea, Italy, Iran, and Brazil. Most patients were intubated in the intensive care unit. Rapid sequence induction was mostly used for intubation. ROX HGNC index might be utilized for the predictor of the necessity of intubation in COVID-19 MESHD patients. According to the previous studies the rate of intubation reported 5 to 88%. It was revealed that 1.4 - 44.5% of patients might be extubated. Yet obesity MESHD and age (elderly) are the only risk factors of delayed or difficult extubation. Discussion and conclusion: Acute respiratory distress in COVID-19 MESHD patients could require endotracheal intubation and mechanical ventilation. Severe respiratory distress MESHD, loss of consciousness MESHD, and hypoxia MESHD were the most important reasons for intubation. Also, increased levels of ferritin, d-dimer, and lipase in common with hypoxia MESHD are correlated with intubation and ICU admission Mortality following intubation is reported to be 15 to 36%. Awake-prone positioning in comparison to high-flow nasal oxygen therapy did not reduce the risk of intubation and mechanical ventilation. There was no association between intubation timing and mortality of infected MESHD patients. noninvasive ventilation may have survival benefits. Keywords: Intubation, COVID-19 MESHD, critical care, respiratory disease MESHD, infectious disease MESHD, hypoxia MESHD, airway management.

    CERC-002, a human anti-LIGHT mAb reduces respiratory failure MESHD and death MESHD in hospitalized COVID-19 MESHD ARDS MESHD patients

    Authors: David S. Perlin; Garry A. Neil; Colleen Anderson; Inbal Zafir-Lavie; Lori Roadcap; Shane Raines; Carl Ware; Jeffrey Wilkins

    doi:10.1101/2021.04.03.21254748 Date: 2021-04-07 Source: medRxiv

    Background Severe COVID-19 MESHD infection is associated with dysregulated MESHD immune response which, in a substantial minority of patients, results in cytokine release syndrome ( CRS MESHD) and acute respiratory distress syndrome MESHD ( ARDS MESHD). Inhibition of cytokines or cytokine-associated signal transduction is a promising strategy to ameliorate ARDS MESHD associated with CRS. We and others have previously shown that serum free LIGHT ( TNFSF14 HGNC) levels are markedly elevated in patients with COVID-19 MESHD pneumonia MESHD/ARDS10,11, suggesting that LIGHT neutralization may offer therapeutic benefit to COVID-19 MESHD ARDS MESHD patients. Methods We conducted a randomized, double-blind, placebo-controlled, multi-center, proof-of-concept clinical trial of CERC-002 in adults with mild to moderate ARDS MESHD associated with COVID-19 MESHD (n=83). Enrolled patients received a single dose of CERC-002 or placebo, in addition to standard of care that included high dose corticosteroids. The primary efficacy endpoint was alive and free of respiratory failure MESHD status through Day 28. Secondary outcomes included alive status at Day 28, free of invasive ventilation through Day 28, and serum free LIGHT levels. Results In patients hospitalized with COVID-19 MESHD associated pneumonia MESHD and mild to moderate ( ARDS MESHD), CERC-002 increased the rate of alive and free of respiratory failure MESHD status through Day 28 as compared to placebo (83.9% vs 64.5%; p=0.044). Efficacy was highest in the prespecified subgroup of patients 60 years old and older (76.5% vs 47.1%; p=0.042), the population most vulnerable to severe complications and death MESHD with COVID-19 MESHD infection. Through both the initial 28-day and 60-day follow-up periods, reductions of approximately 50% in mortality were observed for CERC-002 compared to placebo (7.7% vs 14.3% at Day 28 and 10.8% vs 22.5% at Day 60). Importantly, this improvement was incremental to standard of care including high dose steroids and remdesivir 88.0% and 57.8%, respectively). In addition, serum LIGHT levels but not IL-6 HGNC levels were markedly reduced in patients treated with CERC-002. Conclusions The data presented herein demonstrate that CERC-002 markedly reduces the risk of respiratory failure MESHD and death incremental MESHD to standard of care including high dose corticosteroids and reduces LIGHT levels in patients with COVID-19 MESHD ARDS MESHD. (ClinicalTrials.gov number NCT04412057).

    Innate immune deficiencies in patients with COVID-19 MESHD

    Authors: Marine Peyneau; Vanessa Granger; Paul-Henri Wicky; Dounia Khelifi-Touhami; Jean-Francois Timsit; Francois-Xavier Lescure; Yazdan Yazdanpanah; Alexy Tran-Dihn; Philippe Montravers; Renato Monteiro; Sylvie Chollet-Martin; Margarita Hurtado-Nedelec; Luc de Chaisemartin

    doi:10.1101/2021.03.29.21254560 Date: 2021-03-31 Source: medRxiv

    COVID-19 MESHD can cause acute respiratory distress syndrome MESHD ( ARDS MESHD), leading to death in a significant number of individuals. Evidence of a strong role of the innate immune system is accumulating, but the precise cells and mechanism involved remain unclear. In this study, we investigated the links between circulating innate phagocyte phenotype and functions and severity in COVID-19 MESHD patients. Eighty-four consecutive patients were included, 44 of which were in intensive care units (ICU). We performed an in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, myeloid cell functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Resulting parameters were linked to disease severity and prognosis. Both ICU and non-ICU patients had circulating neutrophils and monocytes with an activated phenotype, as well as elevated concentrations of soluble activation markers (calprotectin, myeloperoxidase HGNC, neutrophil extracellular traps, MMP9 HGNC, sCD14) in their plasma. ICU MESHD patients were characterized by increased CD10 HGNClow CD13 HGNClow immature neutrophils, LOX-1 HGNC+ and CCR5 HGNC+ immunosuppressive neutrophils, and HLA-DRlow CD14 HGNClow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity and poor outcome. Moreover, neutrophils and monocytes of ICU patients had impaired antimicrobial functions, which correlated with organ dysfunction MESHD, severe infections, and mortality. Our study reveals a marked dysregulation MESHD of innate immunity in COVID-19 MESHD patients, which was correlated with severity and prognosis. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 MESHD severe infections and pleads for targeted therapeutic options.

    Hyperglycemia MESHD in Acute COVID-19 MESHD is Characterized by Adipose Tissue Dysfunction and Insulin HGNC Resistance

    Authors: Moritz Reiterer; Mangala Rajan; Nicolas Gomez-Banoy; Jennifer D Lau; Luis G Gomez-Escobar; Ankit Gilani; Sergio Alvarez-Mullet; Evan T Sholle; Vasuretha Chandar; Yaron Bram; Katherine Hoffman; Alfonso Rubio-Navarro; Skyler Uhl; Alpana P Shukla; Parag Goyal; Benjamin R tenOever; Laura Alonso; Robert E Schwartz; Edward J Schenck; Monika M Safford; James C Lo

    doi:10.1101/2021.03.21.21254072 Date: 2021-03-26 Source: medRxiv

    COVID-19 MESHD has proven to be a metabolic disease MESHD resulting in adverse outcomes in individuals with diabetes MESHD or obesity MESHD. Patients infected with SARS-CoV-2 and hyperglycemia MESHD suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome MESHD ( ARDS MESHD), and increased mortality compared to those who do not develop hyperglycemia MESHD. Nevertheless, the pathophysiological mechanism(s) of hyperglycemia MESHD in COVID-19 MESHD remains poorly characterized. Here we show that insulin HGNC resistance rather than pancreatic beta cell failure MESHD is the prevalent cause of hyperglycemia MESHD in COVID-19 MESHD patients with ARDS MESHD, independent of glucocorticoid treatment. A screen of protein hormones that regulate glucose homeostasis reveals that the insulin sensitizing adipokine adiponectin is reduced in hyperglycemic COVID-19 MESHD patients. Hamsters infected with SARS-CoV-2 also have diminished expression of adiponectin HGNC. Together these data suggest that adipose tissue dysfunction MESHD may be a driver of insulin HGNC resistance and adverse outcomes in acute COVID-19 MESHD.

    Evaluation of albumin kinetics in mechanically ventilated patients with COVID-19 MESHD compared to those with sepsis MESHD-induced ARDS

    Authors: Chang Su; Katherine Hoffman; Zhenxing Xu; Elizabeth Sanchez; Ilias Siempos; John S Harrington; Alexandra Racanelli; Maria Plataki; Fei Wang; Edward J Schenck

    doi:10.1101/2021.03.16.21253405 Date: 2021-03-24 Source: medRxiv

    COVID-19 MESHD outcomes like mortality have been associated with albumin alteration. However, it is unclear whether albumin changes in COVID-19 MESHD are pathogen specific or not. To this end, we characterized the kinetics of serum albumin in mechanically ventilated patients with COVID-19 MESHD compared to mechanically ventilated patients with sepsis-induced Acute Respiratory Distress Syndrome MESHD ( ARDS MESHD). We discovered two phases of alterations in albumin levels during the course of Covid-19 MESHD critical illness, but not for the sepsis MESHD-induced ARDS MESHD. Our findings suggest the metabolic effects of COVID-19 MESHD are pathogen-specific and albumin recovery may signal the cessation of a deleterious immune response in this disease.

    Some Clinical and Immunological Features of Imported COVID-19 MESHD Cases in Mongolia MESHD

    Authors: Tsogtsaikhan Sandag; Enkhsaikhan Lkhagvasuren; Munkhundrakh Batmunkh; Oyungerel Ravjir

    doi:10.1101/2021.03.17.21253849 Date: 2021-03-24 Source: medRxiv

    SARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19 MESHD. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation MESHD in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome MESHD, disseminated intravascular coagulation MESHD and multi-organ failure MESHD. Methods: The serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05. Results: Patients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38{+/-}1.46%) and elevated level of serum CRP (8.57{+/-}19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52{+/-}1.47% and 1.96{+/-}3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged [≥]35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1 HGNC and MCP-1 HGNC (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).

    Circadian regulation of SARS-CoV-2 infection MESHD in lung epithelial cells

    Authors: Xiaodong Zhuang; Senko Tsukuda; Florian Wrensch; Peter AC Wing; Helene Borrmann; James M Harris; Sophie B Morgan; Laurent Mailly; Nazia Thakur; Carina Conceicao; Harshmeena Sanghani; Laura Heydmann; Charlotte Bach; Anna Ashton; Steven Walsh; Tiong Kit Tan; Lisa Schimanski; Kuan-Ying A Huang; Catherine Schuster; Koichi Watashi; Timothy SC Hinks; Aarti Jagannath; Sridhar R Vausdevan; Dalan Bailey; Thomas F Baumert; Jane A McKeating

    doi:10.1101/2021.03.20.436163 Date: 2021-03-21 Source: bioRxiv

    The COVID-19 pandemic MESHD, caused by SARS-CoV-2 coronavirus MESHD, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via binding human angiotensin-converting enzyme ( ACE2 HGNC), and infection can result in pneumonia MESHD and acute respiratory distress syndrome MESHD. Circadian rhythms coordinate an organisms response to its environment and recent studies report a role for the circadian clock to regulate host susceptibility to virus infection MESHD. Influenza A infection of arhythmic mice, lacking the circadian component BMAL1, results in higher viral replication and elevated inflammatory responses leading to more severe bronchitis MESHD, highlighting the impact of circadian pathways in respiratory function. We demonstrate circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with the synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry MESHD and RNA replication. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Our study suggests new approaches to understand and improve therapeutic targeting of COVID-19 MESHD.

    Dual targeting of cytokine storm and viral replication in COVID-19 MESHD by plant-derived steroidal pregnanes in silico

    Authors: Gideon A. Gyebi; Oludare M. Ogunyemi; Ibrahim M. Ibrahim; Saheed O. Afolabi; Joseph O. Adebayo

    doi:10.21203/rs.3.rs-329239/v1 Date: 2021-03-14 Source: ResearchSquare

    The high morbidity and mortality rate of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection MESHD arises majorly from the Acute Respiratory Distress Syndrome MESHD and “cytokine storm” syndrome, which is sustained by an aberrant systemic inflammatory response and elevated pro-inflammatory cytokines. Thus, phytocompounds with broad-spectrum anti-inflammatory activity that target multiple SARS-CoV-2 proteins will enhance the development of effective drugs against the disease. In this study, an in-house library of 106 steriodal plant-derived pregnanes (PDPs) was docked in the active regions of human glucocorticoid receptors (hGRs) in a comparative molecular docking analysis. Based on the minimal binding energy and a comparative dexamethason binding mode analysis, a list of top twenty ranked PDPs docked in the agonist conformation of hGR, with binding energies ranging between -9.8 and -11.2 Kcal/mol, was obtained and analyzed for interactions with the human Janus kinases 1 and Interleukins-6 and SARS-CoV-2 3-chymotrypsin- like protease, Papain PROTEIN-like protease and RNA-dependent RNA polymerase PROTEIN. For each target protein, the top three ranked PDPs were selected. Eight PDPs (bregenin, hirundigenin, anhydroholantogenin, atratogenin A, atratogenin B, glaucogenin A, glaucogenin C and glaucogenin MESHD D) with high binding tendencies to the catalytic residues of multiple targets were identified. A high degree of structural stability was observed from the 100 ns molecular dynamics simulation analyses of glaucogenin C MESHD and hirundigenin complexes of hGR. The selected top-eight ranked PDPs demonstrated favourable druggable and in silico ADMET properties. Thus, the therapeutic potentials of glaucogenin C MESHD and hirundigenin can be explored for further in vitro and in vivo studies.

    Awake prone position in adult nonintubated patients with acute hypoxaemic respiratory failure MESHD secondary to COVID-19 MESHD:A multi-centre feasibility randomized controlled trial

    Authors: Devachandran Jayakumar; Pratheema Ramachandran; Ebenezer Rabindrarajan; Bharathkumar Tirupakuzhi Vijayaraghavan; Ramakrishnan Nagarajan; Ramesh Venkataraman

    doi:10.1101/2021.03.13.21253499 Date: 2021-03-13 Source: medRxiv

    Background: The primary manifestation of Corona Virus Disease MESHD -2019 ( COVID-19 MESHD) is acute hypoxic respiratory failure MESHD secondary to pneumonia and/or acute respiratory distress syndrome MESHD. Prone position has been shown to improve outcomes in ventilated patients with moderate to severe acute respiratory distress syndrome MESHD. The feasibility and safety of awake prone positioning and its impact on outcomes if any, in non-intubated patients with mild to moderate acute respiratory distress syndrome MESHD secondary to COVID-19 MESHD is unknown. Results of the observational studies published thus far in this pandemic have been conflicting. In this context, we conducted a multi-centre, parallel group, randomised controlled feasibility study on awake prone positioning in non-intubated patients with COVID-19 MESHD pneumonia MESHD requiring supplemental oxygen. Methods: 60 patients diagnosed with acute hypoxic respiratory failure MESHD secondary to COVID -19 pneumonia MESHD requiring 4 or more litres of oxygen to maintain a saturation of [≥] 92% were recruited in this study. Thirty patients each were randomised to either standard care or awake prone group. Patients randomised to the standard care were allowed to change their position as per comfort and patients randomized to the prone group were encouraged to self-prone for at least 6 hours a day. The primary outcome was the proportion of patients adhering to the protocol in each group. Secondary outcomes include failure of therapy leading to escalation of respiratory support, number of hours prone, maximum hours of continuous prone positioning in a day, length of stay in ICU, ICU mortality, total number of patients needing intubation and adverse events. Results: In the prone group, 43% (13 out of 30) of patients were able to self-prone for 6 or more hours a day. The median maximum prone duration per session was 2 hours. In the supine group, 47% (14 out of 30) were completely supine and 53% spent some hours in the prone position, but none exceeded 6 hours. There was no significant difference in any of the secondary outcomes between the two groups and there were no adverse events. Interpretation: Awake proning in non-intubated patients with acute hypoxic respiratory failure MESHD is feasible and safe under clinical trial conditions. The results of our feasibility study will potentially help in the design of larger definitive trials to address this key knowledge gap.

    Point-of-care ultrasonography for risk stratification of non-critical suspected COVID-19 MESHD patients on admission (POCUSCO): a prospective binational study

    Authors: Francois Morin; Delphine Douillet; Jean Francois Hamel; Dominique Savary; Christophe Aube; Karim Tazarourte; Kamelia Marouf; Florence Dupriez; Philippe Le Conte; Thomas Flament; Thomas Delomas; Mehdi Taalba; Nicolas Marjanovic; Francis Couturaud; Nicolas Peschanski; Thomas Boishardy; Jeremie Riou; Vincent Dubee; Pierre-Marie Roy

    doi:10.1101/2021.03.09.21253208 Date: 2021-03-11 Source: medRxiv

    Background Lung point-of-care ultrasonography (L-POCUS) is highly effective in detecting pulmonary peripheral patterns and may allow early identification of patients who are likely to develop an acute respiratory distress syndrome MESHD ( ARDS MESHD). We hypothesized that L-POCUS performed during the initial examination would identify non-severe COVID-19 MESHD patients with a high risk of getting worse. Methods POCUSCO was a prospective, multicenter study. Non-critical adult patients who were admitted to the emergency department (ED) for suspected or confirmed COVID-19 MESHD were included and had L-POCUS performed within 48 hours following admission. The severity of lung damage MESHD was assessed using the L-POCUS score based on 36 points for ARDS MESHD. The primary outcome was the rate of patients requiring intubation or who died within 14 days following inclusion. Results Among 296 participating patients, 8 (2.7%) had primary outcome. The area under the curve (AUC) of the receiver operating characteristic of L-POCUS was 0.80 [95%CI:0.60-0.94]. The score values which achieved a sensibility > 95% in defining low-risk patients and a specificity > 95% in defining high-risk patients were <1 and [≥]16, respectively. The rate of patients with an unfavorable outcome was 0/95 (0%[95%CI:0-3.9]) for low-risk patients (score=0) versus 4/184 (2.17%[95%CI:0.8-5.5]) for intermediate-risk patients (score 1-15) and 4/17 (23.5%[95%CI:11.4-42.4]) for high-risk patients (score [≥]16). In patients with confirmed COVID-19 MESHD (n=58), the AUC of L-POCUS was 0.97 [95%CI:0.92-1.00]. Conclusions L-POCUS allows risk-stratification of patients with suspected or confirmed COVID-19 MESHD. These results should be confirmed in a population with a higher risk of an unfavorable outcome.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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