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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (5)

NSP5 (2)

ProteinN (2)

ProteinS1 (2)

NSP3 (1)


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    Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association With Viral Load, Independent of Symptoms

    Authors: Arnaud Didierlaurent; Vu Diem-Lan; Paola Martinez Murillo; Fiona Pigny; Maria Vono; Benjamin Meyer; Christiane S Eberhardt; Sylvain Lemeille; Elodie Von Dach; Geraldine Blanchard-Rohner; Isabella Eckerle; Angela Huttner; Claire-Anne Siegrist; Laurent Kaiser

    doi:10.21203/rs.3.rs-203414/v1 Date: 2021-02-04 Source: ResearchSquare

    Background SARS-CoV-2 infection MESHD leads to high viral loads in the upper respiratory tract that may be determinant in virus dissemination. The extent of intranasal antiviral response in relation to symptoms is unknown. Understanding how local innate responses control virus is key in the development of therapeutic approaches. MethodsSARS-CoV-2-infected MESHD patients were enrolled in an observational study conducted at the Geneva University Hospitals, Switzerland, investigating virological and immunological characteristics. Nasal-wash and serum specimens from a subset of patients were collected to measure viral load and a cytokine panel at different time points after infection; cytokine levels were analyzed in relation to symptoms.ResultsSamples from 13 SARS-CoV-2-infected MESHD patients and six controls were analyzed. We found an increase in CXCL10 HGNC and IL-6 HGNC, whose levels remained elevated for up to 3 weeks after symptom onset. SARS-CoV-2 infection MESHD also induced CCL2 HGNC and GM-CSF HGNC, suggesting local recruitment and activation of myeloid cells. Local cytokine levels correlated with viral load but not with serum cytokine levels, nor with specific symptoms, including anosmia.ConclusionsThe nasal MESHD epithelium is an active site of cytokine response against SARS-CoV-2 that can last more than 2 weeks; in this cohort, anosmia MESHD was not associated with increases in any locally produced cytokines.

    Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike PROTEIN glycoprotein S1 and its inhibition by dexamethasone

    Authors: Olumayokun A Olajide; Victoria U Iwuanyanwu; Izabela Lepiarz-Raba; Alaa A Al-Hindawi

    doi:10.1101/2021.02.03.429536 Date: 2021-02-03 Source: bioRxiv

    An understanding of the pathological inflammatory mechanisms involved in SARS CoV-2 virus infection MESHD is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 spike PROTEIN glycoprotein. In this study, the effects of a recombinant SARS CoV-2 spike PROTEIN glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation with spike glycoprotein S1 PROTEIN (100 ng/mL) resulted in significant elevation in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC. However, pre-treatment with dexamethasone (100 nM) caused a significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-{kappa}B HGNC p65 HGNC and I{kappa}B, while increasing I{kappa}B degradation. DNA binding of NF-{kappa}B HGNC p65 HGNC was also significantly increased following stimulation with S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 M) resulted in inhibition of S1-induced NF-{kappa}B HGNC activation. Activation of p38 HGNC MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment produced significant inhibition of S1-induced activation of NLRP3 HGNC/ caspase 1 HGNC. Further experiments revealed that S1-induced increase in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1{beta HGNC} production. These results suggest that SARS-CoV-2 spike PROTEIN glycoprotein S1 stimulate PBMCs to release pro inflammatory cytokines through mechanisms involving activation of NF-{kappa}B HGNC, p38 MAPK and NLRP3 HGNC inflammasome. It is proposed that clinical benefits of dexamethasone in COVID-19 MESHD is possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.

    Successful Treatment of Convalescent Plasma Therapy in Three Patients With Severe SARS-CoV-2 Infection MESHD SARS-CoV-2 Infection MESHD in Fuzhou, China

    Authors: Di Wu; Xiaolin Zhu; Songjing Shi; Fenghui Lin; Baosong Xie; Guoxiang Lai; Lizhou Chen

    doi:10.21203/rs.3.rs-196885/v1 Date: 2021-02-01 Source: ResearchSquare

    Background Up to now, there is no specific treatment for coronavirus disease 2019 MESHD ( COVID-19 MESHD) yet except for general supportive care. Hence, it will be critical to find a new strategy for COVID-19 MESHD. The study is to explore whether convalescent plasma transfusion may be beneficial in the treatment of severe patients with COVID-19 MESHD.Methods This is a retrospective analysis of three severe patients with laboratory-confirmed COVID-19 MESHD and admitted in Fuzhou pulmonary hospital of Fujian province from February 18th, to May 15th,who met the following criteria: (1) within 3 weeks of symptom onset;laboratory confirmed cases or who had viremia MESHD conformed by clinical experts;(2)Severe patients with rapidly progress or the early stage of critically ill MESHD patients or who required plasma therapy were comprehensively evaluated by clinical experts. The data of clinical manifestations and the progresses of disease monitored by blood-gas analysis, biochemical tests, routine examine, radiological exam were abstracted and then analysis the changes before and after convalescent plasma transfusion. Results All three patients (one male and two females; age range, 57-65years) were treated with convalescent plasma during the study. Two patients had underlying chronic diseases MESHD, including diabetes MESHD and hypertension MESHD. The most common symptoms were fever MESHD (three cases, 3/3) and cough (two cases, 2/3). All patients were treated with a combination of two antiviral drugs (lopinaviritonavir or arbidol combined with IFN- HGNCɑ), whereas none of the patients were given glucocorticoids. Following plasma transfusion, the symptoms of the whole group improved to some degree, mainly manifested as reducing in coughing and body temperature normalized. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.97 × 109/L vs. 1.08 × 109/L) and decreased IL-6 HGNC (41.34 pg/ml vs. 13.83 pg/ml). The density of bilateral infiltration on CT imaging showed varying degrees of absorption within 7days. Throat swab nucleic acid test of most patients became negative for the novel coronavirus within 3 days after the transfusion. No adverse effects and severe complications were observed. Conclusions In this preliminary uncontrolled case series of 3severe patients with COVID-19 MESHD, convalescent plasma could be as a promising therapy for COVID-19 MESHD without corticosteroids and no serious adverse reactions associated with the transfusion of convalescent plasma were observed, which would improve the clinical outcomes following by improvement in their clinical status. Using the convalescent plasma at the early stage(less than 10 days) of disease could be more effective. Anticoagulation is necessary for severe patients with COVID-19 MESHD given the state of hypercoagulability MESHD. However, given the small sample size and limited study design, naturally these results should be taken with a grain of salt until replicated by other further investigation in larger well-controlled trials.

    Early immune pathology and persistent dysregulation MESHD characterise severe COVID-19 MESHD

    Authors: Laura Bergamaschi; Federica Mescia; Lorinda Turner; Aimee Hanson; Prasanti Kotagiri; Benjamin J. Dunmore; Helene Ruffieux; Aloka DeSa; Oisin Huhn; Mark R. Wills; Stephen Baker; Rainer Doffinger; Gordon Dougan; Anne Elmer; Ian G Goodfellow; Ravindra K. Gupta; Myra Hosmillo; Kelvin Hunter; Nathalie Kingston; Paul J. Lehner; Nicholas J. Matheson; Jeremy K. Nicholson; Anna M. Petrunkina; Sylvia Richardson; Caroline Saunders; James E.D. Thaventhiran; Erik J.M. Toonen; Michael P. Weekes; - CambridgeInstituteofTherapeuticImmunologyandInfectiousDisease-NationalInstituteofHealthResearch(CITI; Mark Toshner; Christoph Hess; John R. Bradley; Paul A. Lyons; Kenneth G.C. Smith

    doi:10.1101/2021.01.11.20248765 Date: 2021-01-15 Source: medRxiv

    In a study of 207 SARS-CoV2-infected MESHD individuals with a range of severities followed over 12 weeks from symptom onset, we demonstrate that an early robust immune response, without systemic inflammation MESHD, is characteristic of asymptomatic or mild disease. Those presenting to hospital had delayed adaptive responses and systemic inflammation MESHD already evident at around symptom onset. Such early evidence of inflammation MESHD suggests immunopathology may be inevitable in some individuals, or that preventative intervention might be needed before symptom onset. Viral load does not correlate with the development of this pathological response, but does with its subsequent severity. Immune recovery is complex, with profound persistent cellular abnormalities correlating with a change in the nature of the inflammatory response, where signatures characteristic of increased oxidative phosphorylation and reactive-oxygen species-associated inflammation MESHD replace those driven by TNF HGNC and IL-6 HGNC. These late immunometabolic inflammatory changes and unresolved immune cell defects, if persistent, may contribute to "long COVID".

    Cerebrospinal fluid in COVID-19 MESHD neurological complications: no cytokine storm or neuroinflammation.

    Authors: Maria A. Garcia; Paula V. Barreras; Allie Lewis; Gabriel Pinilla; Lori J. Sokoll; Thomas Kickler; Heba Mostafa; Mario Caturegli; Abhay Moghekar; Kathryn C. Fitzgerald; - Hopkins Neuro-COVID-19 Group; Carlos A Pardo

    doi:10.1101/2021.01.10.20249014 Date: 2021-01-12 Source: medRxiv

    BACKGROUND. Neurological complications MESHD occur in COVID-19 MESHD. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 MESHD subjects with neurological complications MESHD and determine presence of neuroinflammatory changes implicated in pathogenesis. METHODS. Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 MESHD subjects with neurological complications categorized by diagnosis ( stroke MESHD, encephalopathy MESHD, headache MESHD) and illness severity (critical, severe, moderate, mild). COVID-19 MESHD CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders MESHD and stroke MESHD controls (n=82). Cytokines ( IL-6 HGNC, TNF-alpha HGNC, IFN-gamma HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC), inflammation MESHD and coagulation markers (high-sensitivity- C Reactive Protein HGNC [hsCRP], ferritin, fibrinogen HGNC, D-dimer, Factor VIII) and neurofilament light chain ( NF-L HGNC), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. RESULTS. CSF from COVID-19 MESHD subjects showed a paucity of neuroinflammatory changes, absence of pleocytosis MESHD or specific increases in pro-inflammatory markers or cytokines ( IL-6 HGNC, ferritin, or D-dimer). Anti-SARS-CoV2 antibodies in CSF of COVID-19 MESHD subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. A similar increase of pro-inflammatory cytokines ( IL-6 HGNC, TNF-alpha HGNC;, IL-12p70) and IL-10 HGNC in CSF of COVID-19 MESHD and non- COVID-19 MESHD stroke MESHD subjects was observed compared to controls. CSF-NF-L was elevated in subjects with stroke MESHD and critical COVID-19 MESHD. CSF-hsCRP was present almost exclusively in COVID-19 MESHD cases. CONCLUSION. The paucity of neuroinflammatory changes in CSF of COVID-19 MESHD subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation MESHD in pathogenesis of neurological complications in COVID-19 MESHD. Elevated CSF-NF-L indicates neuroaxonal injury MESHD in COVID-19 MESHD cases. The role of CSF SARS-CoV2 IgG antibodies is still undetermined.

    SARS-CoV-2 spike PROTEIN glycoprotein S1 induces neuroinflammation in BV-2 microglia

    Authors: Olumayokun A Olajide; Victoria U Iwuanyanwu; Oyinkansola D Adegbola; Oliver Artz; Daniele Rosado; Tara Skopelitis; Munenori Kitagawa; Ullas V Pedmale; David Jackson

    doi:10.1101/2020.12.29.424619 Date: 2020-12-29 Source: bioRxiv

    The emergence of SARS-CoV-2 has resulted in a global pandemic. In addition to respiratory complications as a result of SARS-CoV-2 illness MESHD, accumulating evidence suggests that neurological and neuropsychiatric symptoms MESHD are associated with the disease caused by the virus. In this study, we investigated the effects of the SARS-CoV-2 spike PROTEIN glycoprotein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and iNOS HGNC/NO. SARS-CoV-2 spike PROTEIN glycoprotein S1 increased protein expressions of phospho-p65 and phospho-I{kappa}B, as well as enhancing DNA binding and transcriptional activity of NF-{kappa}B HGNC. Pro-inflammatory effects of the glycoprotein effects were reduced in the presence of BAY11-7082 (1 M). The presence of SARS-CoV-2 spike PROTEIN glycoprotein S1 in BV-2 microglia increased the protein expression of NLRP3 HGNC, as well as caspase-1 HGNC activity. However, pre-treatment with CRID3 (1 M) or BAY11-7082 (1 M) resulted in the inhibition of NLRP3 HGNC inflammasome/ caspase-1 HGNC. It was also observed that CRID3 attenuated SARS-CoV-2 spike PROTEIN glycoprotein S1-induced increase in IL-1{beta HGNC} production. Increased protein expression of p38 MAPK was observed in BV-2 microglia stimulated with the spike glycoprotein S1 PROTEIN, and was reduced in the presence of SKF 86002. These results have provided the first evidence demonstrating SARS-CoV-2 spike PROTEIN S1 glycoprotein-induced neuroinflammation in BV-2 microglia. We propose that promotion of neuroinflammation by this glycoprotein is mediated through activation of NF-{kappa}B HGNC, NLRP3 HGNC inflammasome and p38 MAPK. These results are significant because of their relevance to our understanding of neurological and neuropsychiatric symptoms MESHD observed in patients infected with SARS-CoV-2.

    First-described recently discovered non-toxic vegetal-derived furocoumarin preclinical efficacy against SARS-CoV-2: a promising antiviral herbal drug.

    Authors: Ivan Jose Galindo-Cardiel; Adriana Toledo Nunez; Maria Celaya Fernandez; Ariel Ramirez Labrada; Iratxe Uranga-Murillo; Maykel Arias Cabrero; Julian Pardo; Ezio Panzeri; Peter Inglesby; Chris Bates; David Evans; Tom Ward; Jonathan Cockburn; Simon Davy; Krishnan Bhaskaran; Anna Schultze; Christopher T Rentsch; Elizabeth Williamson; William Hulme; Helen I McDonald; Laurie Tomlinson; Rohini Mathur; Henry Drysdale; Rosalind M Eggo; Kevin Wing; Angel Wong; Harriet Forbes; John Parry; Frank Hester; Sam Harper; Stephen JW Evans; Ian J Douglas; Liam Smeeth; Ben Goldacre

    doi:10.1101/2020.12.04.410340 Date: 2020-12-04 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is the aetiology of coronavirus disease 2019 MESHD ( COVID19 MESHD) pandemic. ICEP4 purified compound (ICEP4) is a recently discovered furocoumarin-related purified compound derived from the roots and seeds of Angelica archangelica (herbal drug). ICEP4-related herbal preparations have been extensively used as active herbal ingredients in traditional medicine treatments in several European countries. Extraction method of patent pending ICEP4 (patent application no. GB2017123.7) has previously shown strong manufacturing robustness, long-lasting stability, and repeated chemical consistency. Here we show that ICEP4 presents a significant in vitro cytoprotective effect in highly virulent-SARS-CoV-2 challenged Vero E6 cellular cultures, using doses of 34.5 and 69 M. No dose-related ICEP4 toxicity MESHD was observed in Vero E6 cells, M0 macrophages, B, CD4+ T and CD8+ T lymphocytes, Natural Killer (NK) or Natural Killer T MESHD ( NKT MESHD) cells. No dose-related ICEP4 inflammatory response was observed in M0 macrophages quantified by IL6 HGNC and TNF release in cell supernatant. No decrease in survival rate was observed after either 24 hr acute or 21-day chronic exposure in in vivo toxicity MESHD studies performed in C. elegans. Therefore, ICEP4 toxicological profile has demonstrated marked differences compared to others vegetal furocoumarins. Successful ICEP4 doses against SARS-CoV-2-challenged cells are within the maximum threshold of toxicity MESHD concern (TTC) of furocoumarins as herbal preparation, stated by European Medicines Agency (EMA). The characteristic chemical compounding of ICEP4, along with its safe TTC, allow us to assume that the first-observation of a natural antiviral compound has occurred. The potential druggability of a new synthetic ICEP4-related compound remains to be elucidated. However, well-established historical use of ICEP4-related compounds as herbal preparations may point towards an already-safe, widely extended remedy, which may be ready-to-go for large-scale clinical trials under the EMA emergency regulatory pathway. To the best of the authors knowledge, ICEP4-related herbal drug can be postulated as a promising therapeutic treatment for COVID19 MESHD.

    Network of “drug-target-SARS-CoV-2 Related Genes” Through Integrated Analysis of Pharmacology and Geo Database

    Authors: Jin ping Hou; Yong heng Wang; Yu meng Chen; Yi hao Chen; Xiao Zhu; Rui si Qin; Tingting Chen

    doi:10.21203/rs.3.rs-117894/v1 Date: 2020-11-28 Source: ResearchSquare

    BackgroundCoronavirus Disease MESHD Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) respiratory disease MESHD rapidly caused a global pandemic and social and economic disruption. The combination of Traditional Chinese medicine (TCM) and Conventional Western medicine (CWM) is more effective for COVID-19 MESHD treatment. Moreover, TCM and CWM are important data source for developing new drug targets and promote strategies treat SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs. However, many studies have analyzed the therapeutic mechanism of CWM or TCM alone for COVID-19 MESHD, it is still unclear the interaction mechanism between TCM and CWM on COVID-19 MESHD.MethodsThis paper integrates network pharmacology and GEO database to mine and identify COVID-19 MESHD molecular therapeutic targets, providing potential targets and new ideas for COVID-19 MESHD gene therapy and new drug development. It includes: 1) using TCMSP, TTD, PubChem and CTD databases to analyze drug interactions and associated phenotypes for SARS-CoV-2, to correlate drug and disease interaction mechanisms to screen key drug targets; 2) using GEO database to correlate differential genes and drug targets to screen potential antiviral gene therapy targets, to construct regulatory network and key points of SARS-CoV-2 therapeutic drugs; 3) using computer simulation of molecular docking to screen virus-related proteins for new drugs. ResultsIntegrated analysis of network pharmacology discovered that baicalein, estrone and quercetin are the pivotal active ingredients in TCM and CWM. Combining drug target genes in pharmacology database and virus induced genes in GEO database, the result showed the core hub genes related to COVID-19 MESHD: STAT1 HGNC, IL1B HGNC, IL6 HGNC, IL8 HGNC, PTGS2 HGNC and NFKBIA HGNC, and these genes were significantly downregulated in A549 and NHBE cells by SARS-CoV-2 infection MESHD. Moreover, chemical interaction and molecular docking analysis of hub genes showed that folic acid might as be potential therapeutic drug for COVID-19 MESHD treatment, and SARS-CoV-2 nucleocapsid phosphoprotein was a potential drug target. The network of “drug-target-SARS-CoV-2 related genes” provide noval potential compounds and targets for further studies of SARS-CoV-2.ConclusionsIntegrated analysis of network pharmacology and big data mining provided noval potential compounds and targets for further studies of SARS-CoV-2. Our research implied folic acid and SARS-CoV-2 N as therapeutic target in TCM and CWM. Our research also suggests that targeting SARS-CoV-2 N MESHD N protein PROTEIN is likely to be a common mechanism of TCM and CWM. On the one hand, the identification of pivotal genes provides a target for COVID-19 MESHD molecular therapy, on the other hand, it provides ideas for the analysis of interaction mechanism between virus and host.

    Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection MESHD

    Authors: Nina Le Bert; Hannah E Clapham; Anthony T Tan; Wan Ni Chia; Christine YL Tham; Jane M Lim; Kamini Kunasegaran; Linda Tan; Charles-Antoine Dutertre; Nivedita Shankar; Joey ME Lim; Louisa Jin Sun; Marina Zahari; Zaw M Tun; Vishakha Kumar; Beng Lee Lim; Siew Hoon Lim; Adeline Chia; Yee-Joo Tan; Paul Anantharajah Tambyah; Shirin Kalimuddin; David CB Lye; Jenny GH Low; Lin-Fa Wang; Wei Yee Wan; Li Yang Hsu; Antonio Bertoletti; Clarence C Tam; Martina Recalde; Paula Casajust; Jitendra Jonnagaddala; Vignesh Subbian; David Vizcaya; Lana YH Lai; Fredrik Nyberg; Daniel R. Morales; Jose D. Posada; Nigam H. Shah; Mengchun Gong; Arani Vivekanantham; Aaron Abend; Evan P Minty; Marc A. Suchard; Peter Rijnbeek; Patrick B Ryan; Daniel Prieto-Alhambra

    doi:10.1101/2020.11.25.399139 Date: 2020-11-27 Source: bioRxiv

    The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection MESHD without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 MESHD patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M PROTEIN, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion ( IL-2 HGNC, IFN-{gamma HGNC}, IL-4 HGNC, IL-6 HGNC, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma HGNC} and IL-2 HGNC production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 HGNC and pro-inflammatory cytokines ( IL-6 HGNC, TNF HGNC- and IL-1{beta} HGNC) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected MESHD individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 HGNC might help to reduce inflammatory events during viral clearance.

    Prognostic value of thrombin HGNC generation parameters in hospitalized COVID-19 MESHD patients 

    Authors: María Eugenia de la Morena-Barrio; Carlos Bravo-Pérez; Antonia Miñano; Belén de la Morena-Barrio; María Piedad Fernandez-Perez; Enrique Bernal; José Miguel Gómez-Verdu; María Teresa Herranz; Vicente Vicente; Javier Corral; María Luisa Lozano

    doi:10.21203/rs.3.rs-115220/v1 Date: 2020-11-24 Source: ResearchSquare

    Background. SARS-CoV-2 infection MESHD ARS-CoV-2 infection increases MESHDthe risk of t hrombosis MESHDby different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with t hromboembolic MESHDrisk and unfavorable prognosis. Objective. We aim to systematically and comprehensively evaluate the association between t hrombin HGNCgeneration parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 MESHD patientsMethods. A total of 127 hospitalized patients with confirmed COVID-19 MESHD, 24 hospitalized patients with SARS-CoV-2-negative p neumonia MESHDand 12 healthy subjects were included. Clinical characteristics, t hrombin HGNCgeneration triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed.Results. Despite the frequent use of heparin, COVID-19 MESHD patients had similar t hrombin HGNCgeneration than healthy controls. In COVID-19 MESHD patients, the t hrombin HGNCgeneration lag-time positively correlated with markers of cell lysis (LDH), i nflammation MESHD(CRP, I L-6) HGNC and coagulation (D-dimer), while the endogenous t hrombin HGNCpotential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with f ibrinogen HGNClevels. Patients with more prolonged lag-time and decreased ETP presented with increased ISTH-DIC scores, and had more severe disease (vascular events and d eath) MESHD. The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p=0.006), and with the occurrence of major adverse events (composite end-point of vascular events and d eath) MESHD (HR 2.38; p=0.004).Conclusions. The t hrombin HGNCgeneration ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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