BACKGROUND: We recently described mortality of cardiac injury MESHD in COVID-19 MESHD patients. Admission activation of immune, thrombotic MESHD biomarkers and their ability to predict cardiac injury MESHD and mortality patterns in COVID-19 MESHD is unknown. METHODS: This retrospective cohort study included 170 COVID-19 MESHD patients with cardiac injury MESHD at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS: Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death MESHD were elevate levels of interleukin 6 HGNC ( IL-6 HGNC) (p<0.0001), Tumor Necrosis Factor-a HGNC Tumor Necrosis Factor-a MESHD ( TNF-a HGNC) (p=0.0025), and C-reactive protein HGNC ( CRP HGNC) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic MESHD pathway activation. Increasing cTnI HGNC levels were associated with those of increasing IL-6 HGNC (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS: In COVID-19 MESHD patients with cardiac injury MESHD, admission IL-6 HGNC and D-dimer predicted subsequent elevation of cTnI HGNC and early death MESHD, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury MESHD.

RationaleAngiotensin-converting enzyme 2 ( ACE2 HGNC) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 HGNC influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is unknown. ObjectiveTo measure circulating ACE2 HGNC and ACE HGNC levels in COVID-19 MESHD patients and investigate association with risk factors, outcome and inflammatory markers. Methods and resultsSoluble ACE2 HGNC (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 MESHD patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand MESHD Von Willebrand HGNC factor ( VWF HGNC), factor VIII ( fVIII HGNC), D-dimer, interleukin 6 ( IL-6 HGNC), tumor necrosis MESHD factor and plasminogen activator inhibitor 1 ( PAI-1 HGNC) had previously been determined. Levels of sACE2 were higher in COVID-19 MESHD patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19 MESHD. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes MESHD and patients on RAS-inhibition. sACE was marginally lower during COVID-19 MESHD compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 MESHD correlated with VWF HGNC, fVIII HGNC and D-dimer, while sACE correlated with IL-6 HGNC, TNF HGNC and PAI-1 HGNC. ConclusionssACE2 was transiently elevated in COVID-19 MESHD, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 MESHD differed distinctly in their correlations with markers of inflammation MESHD and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.

Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which can infect several organs and lead to loss of vital organ function, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 MESHD is myocardial injury MESHD, caused both directly and indirectly by SARS-CoV-2, and which is associated with a high risk of mortality. One of the hallmarks of severe COVID-19 MESHD is the "cytokine storm", at which point the immune system malfunctions, leading to possible organ failure MESHD and death MESHD. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) on SARS-CoV-2-infected MESHD human iPSC-derived cardiomyocytes (hiPSC-CMs). Although WIN did not modulate angiotensin-converting enzyme II, nor reduced SARS-CoV-2 infection MESHD and replication in hiPSC-CMs at the conditions tested, it had anti-inflammatory and protective effects by reducing the levels of interleukins 6, 8,18 and tumor necrosis factor-alpha HGNC tumor necrosis factor-alpha MESHD ( TNF HGNC-) and lactate dehydrogenase (LDH) activity in these cells without causing hypertrophic cardiac damage MESHD. These findings suggest that cannabinoids should be further investigated as an alternative therapeutic tool for the treatment of COVID-19 MESHD. HighlightsO_LIHuman iPSC-derived cardiomyocytes (hiPSC-CMs) express CB1 HGNC receptor. C_LIO_LIThe cannabinoid receptor agonist, WIN 55,212-2 (WIN), does not influence SARS-CoV-2 infection MESHD in hiPSC-CMs. C_LIO_LIWIN reduces inflammation MESHD and death MESHD in SARS-CoV-2-infected hiPSC-CMs MESHD. C_LI

The COVID-19 pandemic MESHD is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins closely associated with the prognosis of COVID-19 MESHD. We observed 27 proteins to be differentially expressed between the cohorts of severely ill COVID-19 MESHD patients with adverse and favorable prognosis. Ingenuity pathway analysis revealed that 15 out of the 27 proteins might be regulated by cytokine signalling relevant to interleukin (IL)-1b HGNC, IL-6 HGNC and tumor necrosis factor HGNC tumor necrosis factor MESHD ( TNF HGNC), and their differential expression was possibly implicated in the systemic inflammatory response and cardiovascular disorders MESHD. We further evaluated the practical prognosticators for the clinical prognosis of severe COVID-19 MESHD patients. Subsequent ELISA analyses further uncovered that CHI3L1 HGNC and IGFALS HGNC could be potent prognostic markers with a high sensitivity. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 MESHD patients and provide appropriate treatment based on their predicted prognosis.

Recent studies have been demonstrated that the excessive inflammatory response is an important factor of death in COVID-19 MESHD patients. In this study, we proposed a network representation learning-based methodology, termed AIdrug2cov, to discover drug mechanism and anti-inflammatory response for patients with COVID-19 MESHD. This work explores the multi-hub characteristic of a heterogeneous drug network integrating 8 unique networks. Inspired by the multi-hub characteristic, we design three billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Using the representation vectors, AIdrug2cov identifies 40 potential targets and 22 high-confidence drugs that bind to tumor necrosis factor(TNF)-α HGNC tumor necrosis factor(TNF)-α MESHD or interleukin(IL)-6 HGNC to prevent excessive inflammatory responses in COVID-19 MESHD patients. Finally, we analyze mechanisms of action based on PubMed publications and ongoing clinical trials, and explore the possible binding modes between the new predicted drugs and targets via docking program. In addition, the results in 5 pharmacological application suggested that AIdrug2cov significantly outperforms 5 other state-of-the-art network representation approaches, future demonstrating the availability of AIdrug2cov in drug development field. In summary, AIdrug2cov is practically useful for accelerating COVID-19 MESHD therapeutic development. The source code and data can be downloaded from https://github.com/pengsl-lab/AIdrug2cov.git.

INTRODUCTION: Outbreak of the novel COVID-19 MESHD infection identifies both causative agents that threaten global pandemic in 2003 and 2011. It is an enveloped virus with spike (S) protein PROTEIN attached that facilitates its receptor binding on the surface. Although it has brought about the global interest for the researchers and medical practitioner in the identification of potential targets that may be addressed in order to cope up with the situation. In the current study potential role of cytokines and related inflammatory markers have been identified that interplays in the progression of disease in COVID-19 MESHD patients. MATERIALS AND METHODS: Current study substitutes hundred and fifty (n=150) patients with novel- COVID-19 MESHD and hundred (n=100) healthy controls. After getting informed consent serum samples of the participants were collected and analyzed for their significance in the disease progression. Levels of Interleukins i.e., ( IL-1 HGNC,6,8,10,11) and tumor MESHD tumor HGNC necrosis MESHD factor-alpha ( TNF HGNC-) were determined with help of their specific spectrophotometric and ELISA methods. RESULTS: Findings of study show significant increase in the levels of interleukins and TNF HGNC- that signifies the presence of cytokine storm in worsening the condition in respect to the exposure of COVID-19 MESHD. Levels of IL-1 and 6 were significantly higher in patients (98.69 pg/ml and 71.95 pg/ml) as compared to controls (30.06 pg/ml and 9.46 pg/ml) where, (p=0.001 and 0.007). It also suggests that IL-6 HGNC is most sensitive test with about (98%) sensitivity in comparison with 96%,95%, 95%,93% and 92% in case of IL-10,1,8,11 and TNF-a HGNC respectively. CONCLUSION: Current study elucidate the effects of cytokines and respective inflammatory markers in the progression of the COVID-19 MESHD. Findings show that activation of macrophages and neutrophils have significant role in the worsening of the symptoms and progression of the viral infection MESHD. Thus, use of certain blockers in initial stages could serve with potent benefits in coping up the infectious condition.

Background: Biomarkers that would help prognosticate outcomes and guide treatment of patients with severe coronavirus disease 2019 MESHD ( COVID-19 MESHD) are currently required. We aimed to investigate whether the dynamic variation of cytokines was associated with the survival of patients admitted to an intensive care unit (ICU).Methods: A retrospective study was performed on 40 patients with COVID-19 MESHD admitted to an ICU in Wuhan, China. Demographic, clinical, and laboratory variables were collected, and serum cytokines were kinetically assessed. A multivariable- adjusted generalized linear regression model was used to evaluate the differences in serum cytokine levels between survivor and non-survivors.Results: Among the 40 patients included, a significant positive correlation was found between multiple cytokines. Serum levels of IL-6 HGNC, IL-10 HGNC, and tumor MESHD tumor HGNC necrosis MESHD factor alpha in non-survivors were consistently elevated compared to that of the survivors. Kinetic variations of IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC were associated with a fatal outcome in severe patients with COVID-19 MESHD, independent of sex, age, absolute lymphocyte count, direct bilirubin, hypertension MESHD, chronic obstructive pulmonary disease MESHD, and cancer MESHD.Conclusion: Dynamic changes in serum IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC levels were associated with survival in ICU and could serve as a predictive biomarker in patients with severe COVID-19 MESHD to determine therapeutic options.

To investigate the immune status of people who previously had COVID-19 MESHD infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19 HGNC+ B cells, CD56 HGNC+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, transforming growth factor beta HGNC (TGF-{beta}), tumor MESHD necrosis MESHD factor alpha (TNF-), and interferon gamma ( IFN-{gamma HGNC}) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19 HGNC+ B cells (69.70%), and CD56 HGNC+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 HGNC (100%), IL-4 HGNC (80.88%), IL-6 HGNC (79.41%), IL-10 HGNC (98.53%), TNF HGNC- (89.71%), IFN-{gamma HGNC} (100%) and IL-17 HGNC (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19 HGNC+ B cells, and CD56 HGNC+ NK cells, along with significantly higher levels of IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-10 HGNC, TNF HGNC-, IFN-{gamma} and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19 HGNC+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 HGNC levels, and IL-6 HGNC positively correlated with TNF HGNC- and IFN-{gamma HGNC}. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 MESHD infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

Background: Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19 MESHD. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19 MESHD, and then analyze the active components and potential mechanisms of this herbal pair. Methods: We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19 MESHD, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach, and analyzed the potential mechanisms against COVID-19 MESHD. Finally, the main active compounds in AE were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-COV-2) 3CLpro PROTEIN and angiotensin converting enzyme II (ACE2) for further verification. Result: We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19 MESHD. The results showed that the combination of Amygdalus Communis Vas (ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value, as well as high support degree, which can be used in almost all the stages of COVID-19 MESHD, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19 MESHD. The main active ingredients of AE against COVID-19 MESHD were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 HGNC ( IL-6 HGNC), Mitogen-activated Protein Kinase 1 (MAPK)1 HGNC, MAPK8 HGNC, Interleukin-1β HGNC ( IL-1β HGNC), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit ( RELA HGNC). The protein-protein interaction (PPI) cluster demonstrated that IL-6 HGNC was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The potential pathways mainly involved tumor necrosis MESHD factor ( TNF HGNC), Toll-like receptor (TLR), hypoxia MESHD-inducible factor-1 ( HIF-1 HGNC), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE had good affinity with SARS-COV-2 3CLpro PROTEIN and ACE2, which was consistent with the above analysis. Conclusion: There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19 MESHD. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19 MESHD. AE might have therapeutic effects against COVID-19 MESHD by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage MESHD and other pathological processes through multiple components, targets and pathways.

Background: Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a systemic disease MESHD caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD. The purpose of the present study was to investigate the association between lung injury MESHD and cytokine profile in COVID-19 MESHD pneumonia MESHD.Methods: This retrospective study was conducted in COVID-19 MESHD patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 MESHD with pneumonia MESHD and without pneumonia MESHD. CT severity score and PaO2/FiO2 ratio and were used to assess lung injury MESHD.Results: 106 patients with 12 COVID-19 MESHD without pneumonia MESHD and 94 COVID-19 MESHD with pneumonia MESHD were included. Compared with COVID-19 MESHD without pneumonia MESHD, COVID-19 MESHD with pneumonia MESHD had significant higher serum interleukin (IL)-2R, IL-6 HGNC, and tumor necrosis MESHD tumor necrosis HGNC factor ( TNF HGNC)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R HGNC, and IL-6 HGNC. In multivariate analysis, log IL6 HGNC was only independent explanatory variables for CT severity score (β=0.397, p<0.001) and PaO2/FiO2 (β=-0.434, p=0.003).Conclusions: Elevation of circulating cytokines was significantly associated with presence of pneumonia MESHD in COVID-19 MESHD and the severity of lung injury MESHD in COVID-19 MESHD pneumonia MESHD. Circulating IL-6 HGNC independently predicted the severity of lung injury MESHD in COVID-19 MESHD pneumonia MESHD.