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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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SARS-CoV-2 Proteins
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    Exosomes from COVID-19 MESHD patients carry tenascin-C HGNC and fibrinogen-β in triggering inflammatory signals in distant organ cells

    Authors: Subhayan Sur; Mousumi B. Khatun; Robert Steele; Scott Isbell; Ranjit Ray; Ratna B Ray

    doi:10.1101/2021.02.08.430369 Date: 2021-02-09 Source: bioRxiv

    SARS-CoV-2 infection MESHD causes cytokine storm and overshoot immunity in humans; however, it remains to be determined whether genetic material of SARS-CoV-2 and/or virus induced soluble mediators from lung epithelial cells as natural host are carried out by macrophages or other vehicles at distant organs causing tissue damage. We speculated that exosomes as extracellular vesicles are secreted from SARS-CoV-2 infected MESHD cells may transport messages to other cells of distant organs leading to pathogenic consequences. For this, we took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and SARS-CoV-2 infected MESHD patients. Our results revealed that tenascin-C HGNC ( TNC HGNC) and fibrinogen-{beta} ( FGB HGNC) are highly abundant in exosomes from SARS-CoV-2 infected MESHD patient's plasma as compared to that of healthy normal controls. Since TNC HGNC and FGB HGNC stimulate pro-inflammatory cytokines via NF-kB pathway, we examined the status of TNF-a HGNC, IL-6 HGNC and CCL5 HGNC expression upon exposure of hepatocytes to exosomes from COVID-19 MESHD patients and observed significant increase when compared with that from healthy subjects. Together, our results demonstrated that soluble mediators, like TNC HGNC and FGB HGNC, are transported through plasma exosomes in SARS-CoV-2 infected MESHD patients and trigger pro-inflammatory cytokine expression in cells of distant organs in COVID-19 MESHD patients.

    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.

    The kidnapping of mitochondrial function associated to the SARS-CoV-2 infection MESHD

    Authors: Elizabeth Soria-Castro; María Elena Soto; Verónica; Gustavo Rojas; Mario Perezpeña-Diazconti; Sergio A Críales-Vera; Linaloe Manzano Pech; Israel Pérez-Torres

    doi:10.21203/rs.3.rs-137853/v1 Date: 2020-12-29 Source: ResearchSquare

    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection leads to multiorganic failure MESHD associated with a cytokine storm and septic shock MESHD. The virus evades the mitochondrial production of interferons through its N protein PROTEIN. From that moment on, SARS-CoV-2 hijacks MESHD the functions of this organelle. The aim of this study was to show how the virus kidnaps the mitochondrial machinery for its benefit and survival, altering serum parameters and leading to nitrosative stress (NSS). In a prospective cohort of 15 postmortem patients who died from COVID-19 MESHD, six markers of mitochondrial function; COX II, COX IV HGNC, MnSOD HGNC, nitrotyrosine, Bcl-2 HGNC and caspase-9 HGNC were analyzed by the immune colloidal gold technique in samples from the lung, heart, kidney and liver. Biometric laboratory results from these patients showed alterations in hemoglobin, platelets, creatinine, urea nitrogen, glucose, C-reactive protein HGNC, albumin, D-dimer, ferritin, fibrinogen HGNC, Ca2+, K+, lactate and troponin. These changes were associated with alterations of the mitochondrial structure and function. The multiorganic dysfunction MESHD present in COVID-19 MESHD patients may be caused in part by damage to the mitochondria that results in an inflammatory state that contributes to the elevation of NSS. NSS activates the sepsis MESHD cascade and contributes to the increased mortality in COVID-19 MESHD patients.

    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.

    Haematological factors of SARS-CoV-2 infection MESHD aggravation: a COVID'HEMOS study

    Authors: Paul Billoir; Kevin Alexandre; Thomas Duflot; Maxime Roger; Sebastien Miranda; Odile Goria; Luc Marie Joly; Mathieu Demeyere; Guillaume Feugray; Manuel Etienne; Veronique Le Cam Duchez

    doi:10.21203/rs.3.rs-64302/v1 Date: 2020-08-23 Source: ResearchSquare

    Since December 2019, a pandemic caused by a new coronavirus has spread to more than 170 countries around the world. Worsening infected MESHD patients requiring intensive care unit (ICU) admission, associated with 30% of mortality. A part of worsening is mediated by haemostasis deregulation. The primary aim of this study was to determine if haematological biomarkers, in addition to clinical risk factors on hospital admission, predict worsening (defined by ICU admission and/or death MESHD) in Covid-19 MESHD infected MESHD patients, and secondary, if they could predict the occurrence of thrombotic MESHD events. Thirty-five of the 99 patients got clinically worse and 8 developed pulmonary embolism MESHD ( PE MESHD). Final model of the logistic regression analysis revealed that oxygenodependence (RR=7.27[1.50-19.31]), fibrinogen HGNC levels (RR=1.45[1.17-1.82]), thrombin HGNC peak (RR=1.28[1.03-1.59]), monocytes counts below 0.2 G/L (RR=2.88[1.67-3.19]) and prothrombin fragment 1+2 ( F1+2 HGNC) higher than 290 pM (RR=2.39[1.20-3.30]) were associated with clinical worsening. Fibrinogen HGNC level threshold of 5.5 g/L, thrombin HGNC peak measurement threshold of 99 pM and oxygenodepence allowed prediction of clinical outcome in near than 80% of our cohort. Moreover, using ROC curves, thrombin HGNC peak and F1+2 HGNC on admission with a threshold of 204 nM and 393 pM were sensitive and specific to predict PE MESHD (AUC: 85.7% Se: 70.8% Sp: 100% and AUC: 81.5% Se: 75.0% Sp: 86.8% respectively). In conclusion, we described a rapid decision tree to predict outcome of SARS-CoV-2 infected MESHD patients based on fibrinogen HGNC, TGA HGNC peak and oxygen dependence. Furthermore, thrombin HGNC peak and F1+2 HGNC seem to be specific haematological marker to predict PE MESHD, even in patients with thromboprophylaxis.

    Early initiation of Extracorporeal Blood Purification using the AN69ST (oXiris®) hemofilter as a treatment modality for COVID - 19 patients: a single-centre case series

    Authors: Petar Ugurov; Dijana Popevski; Tanja Gramosli; Dashurie Neziri; Dragica Vuckova; Emil Stoicovski; Lidija Veljanovska-Kiridjievska; Katerina Ignevska; Sanja Mehandziska; Elena Ambarkova; Rodney Alexander Rosalia; Zan Mitrev

    doi:10.21203/rs.3.rs-44717/v1 Date: 2020-07-17 Source: ResearchSquare

    Introduction: Our understanding of the COVID-19 MESHD disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperinflammatory state, systemic coagulopathies MESHD and multiorgan involvement, in particular respiratory distress. We here describe our initial experience with treating of COVID-19 MESHD patients based on early initiation of extracorporeal blood purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 MESHD intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6 HGNC, IL-8 HGNC, TNF-α HGNC, C-Reactive Protein HGNC ( CRP HGNC), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen HGNC, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability MESHD (= elevated Fibrinogen HGNC or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea MESHD, hypoxia MESHD, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure MESHD). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome MESHD. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood cells, stable levels of IL-6 HGNC (< 50 ng/mL) and a decrease of CRP HGNC and Fibrinogen HGNC. Conclusion: Means to monitor COVID-19 MESHD disease severity during hospitalisation are crucial to control disease progression and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood purification may prevent hyperinflammation, thromboembolism MESHD during hospitalisation and thus support clinical recovery. 

    Clinical and biochemical indexes of 11 COVID-19 MESHD patients and the genome sequence analysis of the tested SARS-CoV-2

    Authors: Zhikang Yu; Heming Wu; Qingyan Huang; Xuemin Guo; Zhixiong Zhong

    doi:10.21203/rs.3.rs-32414/v2 Date: 2020-05-29 Source: ResearchSquare

    BackgroundAt present, SARS-CoV-2 epidemic MESHD in the world rapidly spread. It is a serious global public health emergency.MethodsHere we described the clinical characteristics of 11 SARS-CoV-2 infected MESHD patients hospitalized in the Meizhou People's Hospital. And viral genome sequences of SARS-CoV-2 from these patients were analyzed.ResultsOf the 11 patients, six cases developed fever MESHD, nine cases developed cough MESHD, and two cases developed headache MESHD and chills. Four patients (36.4%) had underlying diseases. Pneumonia is the most common complication. The laboratory test results showed that there was no adult patients with increased LYM/LYM%. Most patients had normal total protein (TP) and albumin ( ALB HGNC), but only two patients had decreased. Most patients had increased or normal levels of erythrocyte sedimentation rate (ESR), C reactive protein HGNC ( CRP HGNC), activated partial thromboplastin time (APTT), fibrinogen HGNC (FIB), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH). Neutrophil (NEU) (r=0.664, P=0.026), CK-MB (r=0.655, P=0.029), blood urea nitrogen (BUN) (r=0.682, P=0.021) and SARS-CoV-2 virus cycle threshold (Ct) value were significantly correlated. Multiple sequence alignment (MSA) shows that we identified two different SNPs at positions 8781 and 28144, and have a completely linked genetic form of 8781C-28144T and 8781T-28144C.ConclusionsThe reports of these 11 cases in our hospital will provide useful information for the diagnosis, treatment and drug development of SARS-CoV-2.

    Clinical characteristics and risk factors of patients with severe COVID-19 MESHD in Jiangsu province, China: a retrospective multicentre cohort study

    Authors: Songqiao Liu; Huanyuan Luo; Yuancheng Wang; Luis E. Cuevas; Duolao Wang; Shenghong Ju; Yi Yang

    doi:10.21203/rs.3.rs-23940/v2 Date: 2020-04-20 Source: ResearchSquare

    Background: Coronavirus Disease-2019 ( COVID-19 MESHD) has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 MESHD disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 MESHD and factors associated with severe or critically ill MESHD presentation.Methods: Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections MESHD diagnosed at 24 COVID-19 MESHD-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected at from admission. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 MESHD recorded during hospitalisation.Results: A total of 625 patients, 64 (10.2%) were severe/ critically ill MESHD and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 MESHD were more likely to be older, to be single onset (i.e. not to a cluster of cases in family/community), to have a medical history of hypertension MESHD and diabetes MESHD; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO2), and higher CT image quadrant scores and pulmonary opacity MESHD percentage; had increased C-reactive protein HGNC, fibrinogen HGNC, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03-1.09), lymphocyte count (109/L) (OR 0.25, 95%CI 0.08-0.74), and pulmonary opacity MESHD in CT (per 5%) on admission (OR 1.31, 95%CI 1.15-1.51).Conclusions: Severe or critically ill MESHD patients with COVID-19 MESHD is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity MESHD in CT on admission were associated with risk of severe or critically ill COVID-19 MESHD.

    Machine learning: a predication model of outcome of SARS-CoV-2 pneumonia

    Authors: Gang Wu; Shuchang Zhou; Yujin Wang; Xiaoming Li

    doi:10.21203/rs.3.rs-23196/v1 Date: 2020-04-15 Source: ResearchSquare

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection MESHD is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia MESHD (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) logistic regression model were used for selection of laboratory features. Seven laboratory features selected by machine learning were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen HGNC degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicating outcome of SARS-CoV-2 pneumonia MESHD. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia MESHD with machine learning.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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