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Our study aimed to assess the effect of weekend versus weekday hospital admissions on all-cause mortality in patients with acute myocardial infarction (AMI) and COVID-19 during the COVID-19 pandemic. We analyzed data from the National Inpatient Sample (NIS) 2020, identifying patients with co-existing AMI and COVID-19 admitted on weekdays and weekends. Baseline demographics, comorbidities, and outcomes were assessed. A multivariable regression analysis was conducted, adjusting for confounders to determine the odds of all-cause mortality. Among 74,820 patients, 55,145 (73.7%) were admitted on weekdays, while 19,675 (26.3%) were admitted on weekends. Weekend admissions showed slightly higher proportions of men (61.3% vs. 60%) and whites (56.3% vs. 54.9%) with a median age of 73 years (range: 62-82). The overall all-cause mortality had an odds ratio (OR) of 1.00 (95% CI, 0.92-1.09; P = 0.934). After adjusting for covariates, there was no significant associations between mortality and hospital type (rural: OR = 1.04; 95% CI, 0.78-1.39; P = 0.789; urban teaching: OR = 1.04; 95% CI, 0.94-1.14; P = 0.450) or geographic region (Northeast: OR = 1.16; 95% CI, 0.96-1.39; P = 0.12; Midwest: OR = 0.99; 95% CI, 0.83-1.17; P = 0.871; South: OR = 0.97; 95% CI, 0.85-1.12; P = 0.697; West: OR = 0.94; 95% CI, 0.77-1.15; P = 0.554). There was no significant difference in the rate of all-cause mortality among patients admitted for AMI and COVID-19 between weekdays and weekends.

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OBJECTIVE: To assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DESIGN: Observational study of a historical cohort. SETTING: University hospital in Medellin, Colombia. PARTICIPANTS: Patients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation. INTERVENTIONS: Measurement of VD/VT, CMV, and VR in COVID-19 patients. MAIN VARIABLES OF INTEREST: VD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters. RESULTS: During the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003-1.525; p = 0.046), age (HR 1.024; 95%CI 1.014-1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001-1.07; p = 0.017). CONCLUSIONS: VD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

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Persistent sinus tachycardia (pST) has been associated with adverse cardiovascular events in critically ill patients. Pharmacological control of heart rate with negative inotropic agents has proven to be safe but could be potentially dangerous in patients with concomitant right ventricular (RV) dysfunction. Ivabradine, a medication devoid of negative inotropy, could be a potentially safe solution for this patient population when adequate heart rate control is desired. A 17-year-old male with a history of vaping developed acute respiratory distress syndrome (ARDS) and RV dysfunction, requiring extra corporal life support (ECLS). He suffered from pST. Given his RV dysfunction, a beta-blocker was avoided, and ivabradine was used safely with improvement of his pST. This case demonstrates the efficacy of ivabradine to reduce heart rate and avoid the use of beta-blockers for patients with RV dysfunction, which could be detrimental. Ivabradine was shown to lower the heart rate without altering hemodynamic parameters.

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Background Pulmonary thrombosis and thromboembolism play a significant role in the physiologic derangements seen in COVID-19 acute respiratory failure. The effect of thrombolysis with tenecteplase on patient outcomes is unknown. Methods We conducted a randomized, controlled, double-blind, phase II trial comparing tenecteplase versus placebo in patients with COVID-19 acute respiratory failure (NCT04505592). Patients with COVID-19 acute respiratory failure were randomized to tenecteplase 0.25 mg/kg or placebo in a 2:1 proportion. Both groups received therapeutic heparin for at least 72 hours. Results Thirteen patients were included in the trial. Eight patients were randomized to tenecteplase and five were randomized to placebo. At 28 days, 63% (n = 5) of patients assigned to the treatment group were alive and free from respiratory failure compared to 40% (n = 2) in the placebo arm (p = 0.43). Mortality at 28 days was 25% (n = 2) in the treatment arm and 20% (n = 1) in the control arm (p = 1.0). No patients in the treatment arm developed renal failure by 28 days compared to 60% (n = 3) in the placebo arm (p = 0.07). Major bleeding occurred in 25% (n = 2) of the treatment arm and 20% (n = 1) in the placebo arm; however, no patients in either arm experienced intracranial hemorrhage. Conclusions Tenecteplase with concomitant heparin may improve patient outcomes in patients with COVID-19 respiratory failure. As this study was limited by a small sample size, larger confirmatory studies are needed.

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Coronavirus disease 2019 (COVID-19) often presents with a wide range of complications, including respiratory distress, acute respiratory distress syndrome (ARDS), and hypercoagulable states with resultant cerebrovascular incidents. Intra- and extra-pulmonological shunts can further complicate patient courses, leading to persistent hypoxemia and paradoxical emboli, resulting in potentially life-threatening consequences, necessitating a comprehensive, multidisciplinary approach to patient care. Here we present the case of a 73-year-old male who experienced severe persistent hypoxemic respiratory failure, superimposed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and stroke with a previously undiagnosed patent foramen ovale (PFO) contributing to his clinical presentation.

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The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids.

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Acute respiratory distress syndrome (ARDS) is a severe lung disease associated with a high mortality rate. Extracorporeal membrane oxygenation (ECMO) is a life-saving therapy for severe ARDS patients who do not respond to conventional treatments. Nevertheless, the optimal management of ARDS patients undergoing ECMO and their mortality rates remain subjects of controversy. Thus, this systematic review aims to assess mortality rates in ARDS patients on ECMO and identify associated factors. The review adhered to the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA) 2020 guidelines. A comprehensive literature search was conducted on PubMed, PubMed Central (PMC), Medline, and Embase. In accordance with our inclusion and exclusion criteria, filters, and key terms, we proceeded to screen the articles. After assessing the relevance of each article to our topic, further screening was carried out. Quality assessment of the articles was conducted, resulting in the inclusion of a total of 12 articles for the review. The primary outcome focused on mortality rates among ARDS patients undergoing ECMO. Secondary outcomes explored potential contributors to mortality, including patient age, underlying cause of ARDS, and Sequential Organ Failure Assessment (SOFA) scores at the initiation of ECMO. Mortality rates exhibited significant variation, ranging from 22% to 62.6%. Several factors emerged as potential predictors of mortality, encompassing patient age, comorbidities, complications during ECMO therapy, and treatment-related variables. This systematic review offers valuable insights into the intricate factors influencing mortality rates among ARDS patients on ECMO. A comprehension of these factors is essential to steer clinical practice and enhance patient outcomes. While ECMO serves as a restorative avenue for ARDS patients, future research is warranted to further elucidate these complex interactions and refine ECMO therapy protocols.

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COVID-19 is a severe respiratory disease caused by SARS-CoV-2, a novel human coronavirus. Patients infected with SARS-CoV-2 exhibit heterogeneous symptoms that pose pragmatic hurdles for implementing appropriate therapy and management of the COVID-19 patients and their post-COVID complications. Thus, understanding the impact of infection severity at the molecular level in the host is vital to understand the host response and accordingly it's precise management. In the current study, we performed a comparative transcriptomics analysis of publicly available seven asymptomatic and eight severe COVID-19 patients. Exploratory data analysis employing Principal Component Analysis (PCA) showed the distinct clusters of asymptomatic and severe patients. Subsequently, the differential gene expression analysis using DESeq2 identified 1224 significantly upregulated genes (logFC≥ 1.5, p-adjusted value <0.05) and 268 significantly downregulated genes (logFC≤ -1.5, p-adjusted value <0.05) in severe samples in comparison to asymptomatic samples. Eventually, Gene Set Enrichment Analysis (GSEA) revealed the upregulation of anti-viral and anti-inflammatory pathways, secondary infections, Iron homeostasis, anemia, cardiac-related, etc.; while, downregulation of lipid metabolism, adaptive immune response, translation, recurrent respiratory infections, heme-biosynthetic pathways, etc. Conclusively, these findings provide insight into the enhanced susceptibility of severe COVID-19 patients to other health comorbidities including non-viral pathogenic infections, atherosclerosis, autoinflammatory diseases, anemia, male infertility, etc. owing to the activation of biological processes, pathways and molecular functions associated with them. We anticipate this study will facilitate the researchers in finding efficient therapeutic targets and eventually the clinicians in management of COVID-19 patients and post-COVID-19 effects in them.

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OBJECTIVES: The CytoSorb therapy in COVID-19 (CTC) registry evaluated the clinical performance and treatment parameters of extracorporeal hemoadsorption integrated with veno-venous extracorporeal membrane oxygenation (VV ECMO) in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) and respiratory failure under US FDA Emergency Use Authorization. DESIGN: Multicenter, observational, registry (NCT04391920). SETTING: Intensive care units (ICUs) in five major US academic centers between April 2020 and January 2022. PATIENTS: A total of 100 critically ill adults with COVID-19-related ARDS requiring VV ECMO support, who were treated with extracorporeal hemoadsorption. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, clinical characteristics, laboratory values and outcomes were recorded following individual ethics committee approval at each center. Detailed data on organ support utilization parameters and hemoadsorption treatments were also collected. Biomarker data were collected according to the standard practice at each participating site, and available values were compared before and after hemoadsorption. The primary outcome of mortality was evaluated using a time-to-event analysis. A total of 100 patients (63% male; age 44 ± 11 years) were included. Survival rates were 86% at 30 days and 74% at 90 days. Median time from ICU admission to the initiation of hemoadsorption was 87 h and was used to define two post hoc groups: ≤ 87 h (group-early start, GE) and > 87 h (group-late start, GL). After the start of hemoadsorption, patients in the GE versus GL had significantly shorter median duration of mechanical ventilation (7 [2-26] vs. 17 [7-37] days, p = 0.02), ECMO support (13 [8-24] vs. 29 [14-38] days, p = 0.021) and ICU stay (17 [10-40] vs 36 [19-55] days, p = 0.002). Survival at 90 days in GE was 82% compared to 66% in GL (p = 0.14). No device-related adverse events were reported. CONCLUSIONS: In critically ill patients with severe COVID-19-related ARDS treated with the combination of VV-ECMO and hemoadsorption, 90-day survival was 74% and earlier intervention was associated with shorter need for organ support and ICU stay. These results lend support to the concept of "enhanced lung rest" with the combined use of VV-ECMO plus hemoadsorption in patients with ARDS.

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Introduction: Sepsis is associated with endothelial cell (EC) dysfunction, increased vascular permeability and organ injury, which may lead to mortality, acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). There are no reliable biomarkers to predict these sepsis complications at present. Recent evidence suggests that circulating extracellular vesicles (EVs) and their content caspase-1 and miR-126 may play a critical role in modulating vascular injury in sepsis; however, the association between circulating EVs and sepsis outcomes remains largely unknown. Methods: We obtained plasma samples from septic patients (n=96) within 24 hours of hospital admission and from healthy controls (n=45). Total, monocyte- or EC-derived EVs were isolated from the plasma samples. Transendothelial electrical resistance (TEER) was used as an indicator of EC dysfunction. Caspase-1 activity in EVs was detected and their association with sepsis outcomes including mortality, ARDS and ARF was analyzed. In another set of experiments, total EVs were isolated from plasma samples of 12 septic patients and 12 non-septic critical illness controls on days 1, and 3 after hospital admission. RNAs were isolated from these EVs and Next-generation sequencing was performed. The association between miR-126 levels and sepsis outcomes such as mortality, ARDS and ARF was analyzed. Results: Septic patients with circulating EVs that induced EC injury (lower transendothelial electrical resistance) were more likely to experience ARDS (p<0.05). Higher caspase-1 activity in total EVs, monocyte- or EC-derived EVs was significantly associated with the development of ARDS (p<0.05). MiR-126-3p levels in EC EVs were significantly decreased in ARDS patients compared with healthy controls (p<0.05). Moreover, a decline in miR-126-5p levels from day 1 to day 3 was associated with increased mortality, ARDS and ARF; while decline in miR-126-3p levels from day 1 to day 3 was associated with ARDS development. Conclusions: Enhanced caspase-1 activity and declining miR-126 levels in circulating EVs are associated with sepsis-related organ failure and mortality. Extracellular vesicular contents may serve as novel prognostic biomarkers and/or targets for future therapeutic approaches in sepsis.

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Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.

Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.

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Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys, among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys, and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys, 89 these phytochemicals's potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys. Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys, such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys. We also fully developed the medicinal value of F. dibotrys' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine.

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Purpose: To investigate the association of the maximal severity of pneumonia on CT scans obtained within 6-week of diagnosis with the subsequent development of post-COVID-19 lung abnormalities (Co-LA). Methods: COVID-19 patients diagnosed at our hospital between March 2020 and September 2021 were studied retrospectively. The patients were included if they had (1) at least one chest CT scan available within 6-week of diagnosis; and (2) at least one follow-up chest CT scan available ≥ 6 months after diagnosis, which were evaluated by two independent radiologists. Pneumonia Severity Categories were assigned on CT at diagnosis according to the CT patterns of pneumonia and extent as: 1) no pneumonia (Estimated Extent, 0%); 2) non-extensive pneumonia (GGO and OP, <40%); and 3) extensive pneumonia (extensive OP and DAD, >40%). Co-LA on follow-up CT scans, categorized using a 3-point Co-LA Score (0, No Co-LA; 1, Indeterminate Co-LA; and 2, Co-LA). Results: Out of 132 patients, 42 patients (32%) developed Co-LA on their follow-up CT scans 6-24 months post diagnosis. The severity of COVID-19 pneumonia was associated with Co-LA: In 47 patients with extensive pneumonia, 33 patients (70%) developed Co-LA, of whom 18 (55%) developed fibrotic Co-LA. In 52 with non-extensive pneumonia, 9 (17%) developed Co-LA: In 33 with no pneumonia, none (0%) developed Co-LA. Conclusions: Higher severity of pneumonia at diagnosis was associated with the increased risk of development of Co-LA after 6-24 months of SARS-CoV-2 infection.

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Introduction: A worldwide pandemic infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a deadly disease called COVID-19. Interaction of the virus and the Angiotensin converting-enzyme 2 (ACE2) receptor leads to an inflammatory-induced tissue damage. Thymus vulgaris L. (TvL) is a plant with a long history in traditional medicine that has antimicrobial, antiseptic, and antiviral properties. Thymol and Carvacrol are two important biological components in Thyme that have anti-inflammatory, antioxidant, and immunomodulatory properties. This study is a molecular review on the potential effects of TvL and its active compounds on SARS-COV2 infection. Method: This is a narrative review in which using PubMed, Scopus, ISI, Cochrane, ScienceDirect, Google scholar, and Arxiv preprint databases, the molecular mechanisms of therapeutic and protective effects of TvL and its active compounds have been discussed regarding the molecular pathogenesis in COVID-19. Results: Thyme could suppress TNF-alpha, IL-6, and other inflammatory cytokines. It also enhances the anti-inflammatory cytokines like TGF-beta and IL-10. Thyme extract acts also as an inhibitor of cytokines IL-1-beta and IL-8, at both mRNA and protein levels. Thymol may also control the progression of neuro-inflammation toward neurological disease by reducing some factors. Thyme and its active ingredients, especially Thymol and Carvacrol, have also positive effects on the renin-angiotensin system (RAS) and intestinal microbiota. Conclusions: Accordingly, TvL and its bioactive components may prevent COVID-19 complications and has a potential protective role against the deleterious consequences of the disease.

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Introduction: The National Administration of Traditional Chinese Medicine of the People's Republic of China (NATCM) and the State Administration of Traditional Chinese medicine (TCM) advocated a combination therapy of TCM and anti-viral drugs for novel coronavirus pneumonia (NCP) to improve the efficacy of clinical treatment. Methods: Forty-six patients diagnosed with NCP were sequentially divided into intent-to-treat population: the experimental group (combination of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs; n = 23) and the control group (anti-viral drugs only) (n = 23). The two groups were compared in terms of duration of fever, cough symptom score, fatigue, appetite, dyspnea, out-of-bed activities, chest computer tomography (CT) recovery, virological clearance, average length of hospital stay, and clinical effective rate of drug. After 6 days of observation, patients from the control group were divided into as-treated population: experimental subgroup (n = 14) to obtain clinical benefit and control subgroup (n = 9). Results: There was a significant improvement in the duration of fever (1.087 ± 0.288 vs 4.304 ± 2.490), cough (0.437 ± 0.589 vs 2.435 ± 0.662; P < 0.05), chest CT evaluation (82.6% vs 43.4%; P < 0.05), and virological clearance (60.8% vs 8.7%; P < 0.05) in patients of the experimental group compared with patients in the control group. Further observation in as-treated population reported that cough (0.742 ± 0.463 vs 1.862 ± 0.347; P < 0.05) and fatigue (78.5% vs 33.3%; P < 0.05) were significantly relieved after adding FuXi-Tiandi-Wuxing Decoction to the existing treatment. Conclusion: An early treatment with combination therapy of FuXi-Tiandi-Wuxing Decoction and anti-viral drugs significantly relieves the clinical symptoms of NCP, shows improvement in chest CT scan, improves virological clearance, shortens average length of hospital stay, and reduces the risk of severe illness. The effect of FuXi-Tiandi-Wuxing Decoction in NCP may be clinically important and require further consideration.

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Background: Neonatal acute respiratory distress syndrome (NARDS) was defined in 2017 and the epidemiological data remain unknown. Our objective was to explore aetiological factors, clinical characteristics and outcomes in patients with perinatal NARDS. Methods: A multicentre, prospective, cross-sectional study was performed in 58 tertiary neonatal intensive care units in China from Jan 1, 2018 to June 30, 2019. Neonates diagnosed with NARDS were included. Primary outcomes were aetiological factors, clinical characteristics and outcomes. Binary logistic regression and multivariate cox proportional regression were performed to identify independent predictors for bronchopulmonary dysplasia (BPD) and/or death or single death. This study was registered with ClinicalTrials.Gov, NCT03311165. Findings: Among 70,013 admitted neonates, the incidence of NARDS was 1.44% (1005). The cumulative incidences were 65.6%, 86.7%, 94.1% within one, two and three days after birth. The median gestational age and birth weight were 36.4 weeks and 2700 g. Three main aetiological triggers included pneumonia (58.1%), asphyxia (24.3%) and early-onset sepsis (EOS) (21.3%). BPD and/or death was observed in 213 (21.2%) infants, consisting 104 (10.3%) BPD and 126 (12.6%) deaths. The numbers of mild, moderate and severe NARDS were 537 (53.4%), 286 (28.4%) and 182 (18.2%). Two or more doses of surfactant was associated with increased mortality as compared with one or less doses of surfactant (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.20-3.10, P = 0.006). Similarity also appeared in the comparison between EOS and non-EOS triggers (OR 1.57, 95% CI 1.06-2.33, P = 0.023). Interpretation: NARDS incidence was 1.44% and the three main aetiologies were pneumonia, asphyxia and EOS. The cumulative incidences were 65.6%, 86.7%, and 94.1% within one, two and three days after birth. Our results suggested that two or more doses of surfactant increased mortality compared with one or less doses of surfactant. Funding: The National Clinical Research Center of China and Clinical Medical Study Program of Children's Hospital of Chongqing Medical University (NCRC-2019-GP-13) and Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0197).

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Background and Aims: Gastrointestinal (GI) symptoms are present in 20% of patients with SARS-CoV-2 coronavirus infection (COVID-19). We studied the association of GI symptoms (in patients with COVID-19) with adverse outcomes and factors associated with poor outcomes in these patients. Methods: The study cohort included 100,902 patients from the Cerner Real-World Data COVID-19 Database of hospital encounters and emergency department visits with COVID-19 infection from December 1, 2019, to November 30, 2020. Multivariate analysis was used to study the effect of GI symptoms on adverse outcomes and the factors associated with mortality, acute respiratory distress syndrome (ARDS), sepsis, and ventilator requirement or oxygen dependence in patients with COVID-19 and GI symptoms. Results: Patients with COVID-19 and GI symptoms were significantly more likely to have ARDS (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.11, 1.29), sepsis (OR 1.19, 95% CI 1.14, 1.24), acute kidney injury (OR 1.30, 95% CI 1.24, 1.36), venous thromboembolism (OR 1.36, 95% CI 1.22, 1.52), or GI bleed (OR 1.62, 95% CI 1.47, 1.79) and less likely to experience cardiomyopathy (OR 0.87, 95% CI 0.77, 0.99) or death (OR 0.71, 95% CI 0.67, 0.75). Among those with GI symptoms, older age, higher Charlson comorbidity index scores, and use of proton pump inhibitors/H2 receptor antagonists were associated with higher mortality, ARDS, sepsis, and ventilator or oxygen requirement. Conclusion: Patients with COVID-19 who have GI symptoms have overall worse in-hospital complications but less cardiomyopathy and mortality. Older age, higher comorbidity scores, and the use of proton pump inhibitors and H2 receptor antagonists are associated with poor outcomes in these patients.

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Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) induced cytokine storm is the major cause of COVID-19 related deaths. Patients have been treated with drugs that work by inhibiting a specific protein partly responsible for the cytokines production. This approach provided very limited success, since there are multiple proteins involved in the complex cell signaling disease mechanisms. We targeted five proteins: Angiotensin II receptor type 1 (AT1R), A disintegrin and metalloprotease 17 (ADAM17), Nuclear Factor­Kappa B (NF­κB), Janus kinase 1 (JAK1) and Signal Transducer and Activator of Transcription 3 (STAT3), which are involved in the SARS­CoV­2 induced cytokine storm pathway. We developed machine-learning (ML) models for these five proteins, using known active inhibitors. After developing the model for each of these proteins, FDA-approved drugs were screened to find novel therapeutics for COVID­19. We identified twenty drugs that are active for four proteins with predicted scores greater than 0.8 and eight drugs active for all five proteins with predicted scores over 0.85. Mitomycin C is the most active drug across all five proteins with an average prediction score of 0.886. For further validation of these results, we used the PyRx software to conduct protein-ligand docking experiments and calculated the binding affinity. The docking results support findings by the ML model. This research study predicted that several drugs can target multiple proteins simultaneously in cytokine storm-related pathway. These may be useful drugs to treat patients because these therapies can fight cytokine storm caused by the virus at multiple points of inhibition, leading to synergistically effective treatments.

RESUMEN

COVID-19 is the most devastating disease in recent times affecting most people globally. The higher rate of transmissibility and mutations of SARS-CoV-2 along with the lack of potential therapeutics has made it a global crisis. Potential molecules from natural sources could be a fruitful remedy to combat COVID-19. This systematic review highlights the detailed therapeutic implication of naturally occurring glycyrrhizin and its related derivatives against COVID-19. Glycyrrhizin has already been established for blocking different biomolecular targets related to the SARS-CoV-2 replication cycle. In this article, several experimental and theoretical evidences of glycyrrhizin and related derivatives have been discussed in detail to evaluate their potential as a promising therapeutic strategy against COVID-19. Moreover, the implication of glycyrrhizin in traditional Chinese medicines for alleviating the symptoms of COVID-19 has been reviewed. The potential role of glycyrrhizin and related compounds in affecting various stages of the SARS-CoV-2 life cycle has also been discussed in detail. Derivatization of glycyrrhizin for designing potential lead compounds along with combination therapy with other anti-SARS-CoV-2 agents followed by extensive evaluation may assist in the formulation of novel anti-coronaviral therapy for better treatment to combat COVID-19.

RESUMEN

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without-not much is known about the differences at the histopathological level. To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural distortion was significantly different in immunocompromised; while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.

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