Corpus overview


MeSH Disease

Human Phenotype


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    Early initiation of Extracorporeal Blood SERO 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/ Date: 2020-07-17 Source: ResearchSquare

    Introduction: Our understanding of the COVID-19 disease MESHD has been steadily evolving since the original outbreak in December 2019. Advanced disease MESHD is characterised by a hyperinflammatory state, systemic coagulopathies and multiorgan involvement, in particular respiratory distress HP. We here describe our initial experience with treating of COVID-19 patients based on early initiation of extracorporeal blood SERO purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females TRANS. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease MESHD severity following admission to our dedicated COVID-19 intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6, IL-8, TNF-α, C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen, 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 SERO Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability HP (= elevated Fibrinogen or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea, 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 HP). 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 SERO cells, stable levels of IL-6 (< 50 ng/mL) and a decrease of CRP and Fibrinogen. Conclusion: Means to monitor COVID-19 disease MESHD severity during hospitalisation are crucial to control disease progression MESHD 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 SERO purification may prevent hyperinflammation, thromboembolism MESHD thromboembolism HP during hospitalisation and thus support clinical recovery. 

    The caliber of segmental and subsegmental vessels in COVID-19 pneumonia MESHD pneumonia HP is enlarged: a distinctive feature in comparison with other forms of inflammatory and thromboembolic disease MESHD

    Authors: Maria Chiara Ambrosetti; Giulia Battocchio; Cristiano Fava; Tatjana Bejko; Evelina Tacconelli; Pietro Minuz; Ernesto Crisafulli; Giancarlo Mansueto

    doi:10.21203/ Date: 2020-07-11 Source: ResearchSquare

    Objective: to compare COVID-19 patients’ vessel caliber with that of normal lungs and lungs interested by other inflammatory and thromboembolic processes. Methods: between March and April 2020, 42 patients affected by COVID-19 pneumonia MESHD pneumonia HP [COV-P] underwent a CT scan of the lung at Verona University Hospital for clinical indications. Lung images were compared to 4 different groups of patients (normal lung [NL], distal thromboembolism MESHD thromboembolism HP [DTE], bacterial and fungal pneumonia MESHD pneumonia HP [Bact-P, Fung-P]) by a 4-year-experienced radiologist. Results: COV-P patients’ segmental and subsegmental vessels, as evaluated as the ratio with the corresponding bronchial branch (V/B ratio) were larger with respect to NL, DTE in the apparently healthy parenchyma, a result confirmed in the zones of opacification with respect to Bact-P and Fung-P. Conclusions: This is the first study to comparatively showing that segmental and subsegmental COVID-19 patients’ vessel caliber is significantly enlarged. This is a distinctive feature of COVID-19 pneumonia MESHD pneumonia HP suggesting distinct pathophysiology as compared to other inflammatory and thromboembolic diseases MESHD and alerting radiologists to consider it when evaluating CT scan of suspected patients.

    Tocilizumab and Thromboembolism MESHD Thromboembolism HP in COVID-19: A Retrospective Hospital-based Cohort Analysis

    Authors: Kok Hoe Chan; Bhavik Patel; Bishnu Podel; Maria E Szabela; Hamid S Shaaban; Gunwant Guron; Jihad Slim

    doi:10.21203/ Date: 2020-07-02 Source: ResearchSquare

    Background:Tocilizumab, an IL-6 receptor antagonist has been used in patients with Coronavirus Disease MESHD 2019 (COVID-19) as an anti-cytokine agent. IL-6 also plays a complex role in hemostasis and thrombosis MESHD. We observed a transient elevation of D-dimer in our patients who received Tocilizumab, which triggered the current study.Methods:A retrospective hospital-based cohort analysis of patients with confirmed COVID-19 who received Tocilizumab during the study period of 03/15/2020 to 05/20/2020. We retrieved demographic, clinical and laboratory data, we excluded patients who were receiving therapeutic anticoagulation therapy prior to Tocilizumab administration.  Descriptive analysis was performed, the cause of death MESHD and trends of D-dimer and inflammatory markers were studied. Results: Out of the 436 confirmed COVID 19 patients admitted during the study period, 24 met the inclusion criteria. Their median age TRANS was 47.5 years old. They were 18 males TRANS and 6 females TRANS; 15 patients survived, and 9 expired. Of the group that survived, 12 received therapeutic anticoagulation. Of the 7 patients who did not receive therapeutic anticoagulation, 4 expired, 1 from sepsis MESHD sepsis HP and 3 probably from thromboembolic complications, compared to 5 deaths MESHD in the 17 patients who received therapeutic anticoagulation with 4 dying from sepsis MESHD sepsis HP, and one possibly from thromboembolic complications.Conclusions:The interplay between IL-6, IL-6 receptor antagonist and venous thromboembolism MESHD thromboembolism HP are complex. We observed a transient elevation of D-dimer in COVID-19 patients who received Tocilizumab, and a trend toward increased death MESHD secondary to thromboembolism MESHD thromboembolism HP. This observation is novel and highlights the potential thrombophilic side effects of Tocilizumab.

    A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis MESHD genes' interactions points to Neutrophil Extracellular Traps as mediators of thrombosis MESHD in COVID-19

    Authors: Jun Ding; David Earl Hostallero; Mohamed Reda El Khili; Gregory J Fonseca; Simon Milette; Nuzha Noorah; Myriam Guay-Belzile; Jonathan Spicer; Noriko Daneshtalab; Martin Sirois; Karine Tremblay; Amin Emad; Simon Rousseau

    doi:10.1101/2020.07.01.20144121 Date: 2020-07-02 Source: medRxiv

    Abnormal coagulation and an increased risk of thrombosis MESHD are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis MESHD (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis MESHD. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism MESHD thromboembolism HP to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis MESHD in severe COVID-19 in children TRANS and adults TRANS. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic MESHD and metabolic disorders.

    Assembly of an integrated human lung cell atlas reveals that SARS-CoV-2 receptor is co-expressed with key elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells

    Authors: Davi Sidarta-Oliveira; Carlos Poblete Jara; Adriano J Ferruzzi; Munir S Skaf; William H Velander; Eliana P Araujo; Licio A Velloso

    doi:10.1101/2020.06.02.20120634 Date: 2020-06-04 Source: medRxiv

    SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency MESHD respiratory insufficiency HP, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin-kallikrein system, resulting in acute lung inflammatory edema MESHD edema HP; the renin-angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism MESHD thromboembolism HP. Here we analyzed ~130,000 human lung single-cell transcriptomes and show that key elements of the kinin-kallikrein, renin-angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.

    Olfactory transmucosal SARS-CoV-2 invasion as port of Central Nervous System entry in COVID-19 patients

    Authors: Jenny Meinhardt; Josefine Radke; Carsten Dittmayer; Ronja Mothes; Jonas Franz; Michael Laue; Julia Schneider; Sebastian Bruenink; Olga Hassan; Werner Stenzel; Marc Windgassen,; Larissa Roessler; Hans-Hilmar Goebel; Hubert Martin; Andreas Nitsche; Walter Schulz-Schaeffer; Samy Hakroush; Martin S Winkler; Bjoern Tampe; Sefer Elezkurtaj; David Horst; Lars Oesterhelweg; Michael Tsokos; Barbara Ingold Heppner; Christine Stadelmann; Christian Drosten; Victor M Corman; Helena Radbruch; Frank L Heppner

    doi:10.1101/2020.06.04.135012 Date: 2020-06-04 Source: bioRxiv

    The newly identified severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease MESHD presenting with fever MESHD fever HP, cough MESHD cough HP, and often pneumonia MESHD pneumonia HP. Moreover, thromboembolic events throughout the body including the central nervous system (CNS) have been described. Given first indication for viral RNA presence in the brain and cerebrospinal fluid and in light of neurological symptoms in a large majority of COVID-19 patients, SARS-CoV-2-penetrance of the CNS is likely. By precisely investigating and anatomically mapping oro- and pharyngeal regions and brains of 32 patients dying from COVID-19, we not only describe CNS infarction due to cerebral MESHD thromboembolism MESHD thromboembolism HP, but also demonstrate SARS-CoV-2 neurotropism. SARS-CoV-2 enters the nervous system via trespassing the neuro-mucosal interface in the olfactory mucosa by exploiting the close vicinity of olfactory mucosal and nervous tissue including delicate olfactory and sensitive nerve endings. Subsequently, SARS-CoV-2 follows defined neuroanatomical structures, penetrating defined neuroanatomical areas, including the primary respiratory and cardiovascular control center in the medulla oblongata.

    Lung and Kidney Perfusion Deficits Diagnosed by Dual-Energy Computed Tomography in COVID–19 Patients: Evidence Supporting Systemic Microangiopathy

    Authors: Ilkay S. Idilman; Gulcin Telli Dizman; Selin Ardali Duzgun; Ilim Irmak; Musturay Karcaaltincaba; Ahmet Cagkan Inkaya; Figen Basaran Demirkazik; Gamze Durhan; Meltem Gulsun Akpinar; Orhan Macit Ariyurek; Erhan Akpinar; Jordi Rello; Murat Akova; Deniz Akata

    doi:10.21203/ Date: 2020-05-29 Source: ResearchSquare

    Objectives: There is increasing evidence of thrombotic events occurring in patients with coronavirus disease MESHD (COVID-19). We evaluated dual-energy computed tomography (DECT) findings, particularly lung and kidney perfusion, in non-intubated COVID-19 patients. Methods: Thirty-one COVID-19 patients who underwent pulmonary DECT angiography between March 15 and April 30, 2020, and were suspected of having pulmonary thromboembolism MESHD thromboembolism HP were included. Pulmonary and kidney images were reviewed. Qualitative and quantitative analyses of the perfused blood SERO volume and iodine maps were performed. Results: DECT images showed perfusion deficits (PDs) in eight patients (25.8%), which were not overlapping with areas of ground-glass opacity or consolidation. Two patients had pulmonary thromboembolism MESHD thromboembolism HP confirmed by CT angiography. Five of 10 patients who had been infected for more than 5 days had PDs documented. Patients with PDs had a longer hospital stay (12.25 ± 8.81 vs 6.83 ± 5.04 days, p= 0.14), higher intensive care unit admission rates (37.5% vs 4.3%, p=0.02), higher CT scores (13.3 ± 8.2 vs 5 ± 5.4, p= 0.02) and more severe disease MESHD (50% vs 4.3%, p=0.01). In the PD group, serum SERO ferritin, aspartate aminotransferase (AST), fibrinogen, D-dimer, C-reactive protein (CRP), and troponin levels were significantly higher, whereas albumin level was lower (p<0.05). D-dimer levels ≥ 0.485 ug/L predicted PD with 100% specificity and 87% sensitivity SERO (AUROC: 0.957). Renal iodine maps showed heterogeneous enhancement consistent with perfusion abnormality in 13 patients (50%). Sodium levels were significantly lower in this group (p=0.03). Conclusions: Pulmonary perfusion abnormalities in COVID 19 patients is associated with more severe disease MESHD and in most of the patients can occur without macroscopic pulmonary thromboembolism MESHD thromboembolism HP. High rate of kidney perfusion abnormalities suggests subclinical systemic microvascular obstruction.

    Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

    Authors: Anton S.M. Dofferhoff; Ianthe Piscaer; Leon J. Schurgers; Jona Walk; Jody M.W. van den Ouweland; Tilman M. Hackeng; Pim A. de Jong; Reinoud Gosens; Petra Lux; Henny van Daal; Cecile Maassen; Esther G.A. Maassen; Loes E.M. Kistemaker; Cees Vermeer; Emiel F.M. Wouters; Rob Janssen

    id:10.20944/preprints202004.0457.v2 Date: 2020-05-29 Source:

    Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure HP. Thromboembolism MESHD Thromboembolism HP is also prevalent in coronavirus disease MESHD 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases MESHD. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications HP severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia MESHD pneumonia HP severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications MESHD vascular calcifications HP. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

    A blood SERO-based comprehensive and systems-level analysis of disease MESHD stages, immune regulation and symptoms in COVID-19 patients

    Authors: Anguraj Sadanandam; Tobias Bopp; Santosh Dixit; David JHF Knapp; Chitra Priya Emperumal; Krishnaraj Rajalingam; Alan Melcher; Nagarajan Kannan

    doi:10.21203/ Date: 2020-05-20 Source: ResearchSquare

    COVID-19 patients show significant clinical heterogeneity in presentation and outcomes that makes pandemic control and strategy difficult; optimising management requires a systems biology approach of understanding the disease MESHD. Here we sought to understand and infer complex system-wide changes in patients infected with coronaviruses (SARS-CoV and SARS-CoV-2; n=38 and 57 samples) at two different disease MESHD stages compared with healthy individuals (n=16) and patients with other infections MESHD (n=144). We applied inferential statistics/machine-learning approaches (the COVID-engine platform) to RNA profiles derived from peripheral blood SERO mononuclear cells (PBMCs). Compared to healthy individuals, an integrated blood SERO-based gene signatures distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalisation) from recovering-like patients. These signatures also hierarchically represented systems-level parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle confirmatory observations included PBMC-associated increases in ACE2, cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease MESHD compared to those with recovery-like disease MESHD. Patients in the recovery-like stage had significantly enhanced TNF, IFN-g, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, PBMC-derived surrogate-based approach revealed overlapping genes associated with comorbidities (associated diabetes), and disease MESHD-like symptoms (associated with thromboembolism MESHD thromboembolism HP, pneumonia MESHD pneumonia HP, lung disease MESHD and septicaemia). Overall, our study involving PBMC-based RNA profiling may further help understand complex and variable systems-wide responses displayed by coronavirus-infected patients.

    Aortic Thrombus in patients with Severe Covid-19. Review of three cases

    Authors: Maria Carranza; Danilo Salazar; Jesús Troya; Roberto Alcazar; Cristina Peña; Nuria Muñoz

    doi:10.21203/ Date: 2020-05-12 Source: ResearchSquare

    Coronavirus disease MESHD 2019 (COVID-19) is suspected to predispose to both venous and arterial thromboembolism MESHD thromboembolism HP, in the context of an exaggerated immune response to the virus, especially in severe patients. Even though aortic thrombi are a rare entity, the new COVID-19 establishes the need to include them in the diagnosis, especially in patients with severe disease MESHD and no clinical improvement. Herein, we describe a series of three cases of aortic thrombi diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS CoV-2 infection MESHD.

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MeSH Disease
Human Phenotype

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