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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (14)

NSP5 (4)

ProteinS1 (3)

ProteinN (2)

NSP2 (1)


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    Clinical Course and Outcomes of coronavirus disease 2019 MESHD ( COVID-19 MESHD) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population

    Authors: Timothy L Arleo; David C Tong; Julie M Shabto; Ghazala D O'Keefe; Arezou Khosroshahi

    doi:10.1101/2020.10.26.20219154 Date: 2020-10-27 Source: medRxiv

    Objectives To determine clinical course and outcomes in rheumatic disease MESHD patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD) and compare results to uninfected patients. Methods We conducted a case cohort study of autoimmune disease MESHD patients with COVID-19 MESHD (confirmed by severe acute respiratory syndrome MESHD coronavirus 2 PCR) from 02/01/2020 to 07/31/2020 and compared them in a 1:3 ratio with uninfected patients who were matched based on race, age, sex, and comorbidity index. Patient demographics, clinical course, and outcomes were compared among these patient groups. Results A total of 70 rheumatic disease MESHD patients with COVID-19 MESHD (mean age, 56.6 years; 64% African American) were identified. The 34 (49%) patients who were hospitalized used oral glucocorticoids more frequently (p<0.01). All 10 patients on anti- TNF HGNC medications were treated as outpatients (p<0.01). Those hospitalized with COVID-19 MESHD more often required ICU admission (17 (50%) vs 27 (26%), OR=2.78 (95% CI: 1.24 to 6.20)) and intubation (10 (29%) vs 6 (6%), OR=6.67 (95% CI: 2.20 to 20.16)) than uninfected patients. They also had higher mortality rates (6 (18%) vs 3 (3%), OR=7.21 (95% CI: 1.70 to 30.69)). Of the six COVID-19 MESHD patients who died, one was of African ancestry (p=0.03). Conclusions Rheumatic disease MESHD patients infected with COVID-19 MESHD were more likely to require ICU admission, ventilation, and died more frequently versus uninfected patients with autoimmune disease MESHD. Patients on anti- TNF HGNC medications were hospitalized less frequently while those on chronic glucocorticoids were hospitalized more frequently. These findings have important implications for medication choice in rheumatic disease MESHD patients during the ongoing spread of COVID-19 MESHD.

    TGF-β HGNC and CCL18 HGNC as Indicators for Predicting and Monitoring the Development of Pulmonary Fibrosis in Patients with COVID-19 MESHD

    Authors: Ming Zong; Liang Zheng; Huan Zhou; Liu Lu; Long He; Xiaodong Wu; Nianzhen Chen; Lan Wang; Jiayi Yuan; Erpeng Jiang; Yan Shi; Qiang Li; lieying Fan; Zhongmin Liu

    doi:10.21203/rs.3.rs-97834/v1 Date: 2020-10-24 Source: ResearchSquare

    BackgroundMany COVID-19 MESHD patients have been discharged, but lung injury MESHD, including pulmonary fibrosis MESHD, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis MESHD in patients with COVID-19 MESHD.MethodsThirty-five convalescent patients with severe COVID-19 MESHD, after appropriate medical treatments, were recruited. According to evidence of fibrosis MESHD on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta HGNC ( TGF-β HGNC), chemokine ligand 18 ( CCL18 HGNC), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated.ResultsSevere fibrosis MESHD was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators ( TGF-β HGNC: 66.67±158.57 vs 55.84±126.43 pg/mL, P=0.006; CCL18 HGNC: 364.27±167.70 vs 84.47±60.67 ng/mL, P=0.000; PⅢP: 54.12±55.34 vs 17.15±2.48 ng/mL, P=0.000; HA: 122.47±78.84 vs 59.74±18.01 ng/mL, p=0.000; LN: 55.43±46.44 vs 24.25±7.79 ng/mL, P=0.000; CⅣ: 24.77±14.97 vs 15.32±1.15 ng/mL, P=0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48±16.13 to 10.33±11.11 (P<0.001), and mMRC scores decreased from 3.27±0.32 to 1.48±0.33, and all fibrosis MESHD indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis MESHD. Moreover, TGF-β HGNC and CCL18 HGNC levels were lower in the mild-to-moderate than severe fibrosis MESHD group (88.16±97.45 vs 205.93±170.57 pg/mL, P=0.024; 241.84±125.37 vs 366.64±161.06 ng/mL, P=0.038), and patients with elevated baseline levels of serum TGF-β HGNC and CCL18 HGNC had longer rehabilitation times.ConclusionsTGF-β and CCL18 HGNC may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis MESHD in patients with COVID-19 MESHD.

    Recovery of monocyte exhaustion is associated with resolution of lung injury in COVID-19 MESHD convalescence.

    Authors: Nicholas A Scott; Sean Blandin Knight; Laurence Pearmain; Oliver Brand; David J Morgan; Chris Jagger; Saba Khan; Pamela Hackney; Lara Smith; Madhvi Menon; Joanne Konkel; Halima A Shuwa; Miriam Franklin; Verena Kaestele; Sarah Harbach; Seema Brij; Andrew Ustianowski; Alison Uriel; Gabriella Lindergard; Nawar Diar Bakerly; Paul Dark; Alexander Mathioudakis; Kathryn Gray; Graham Lord; Timothy Felton; Chris Brightling; Ling-Pei Ho; - NIHR Respiratory TRC; - CIRCO; Karen Piper Hanley; Angela Simpson; John R Grainger; Tracy Hussell; Elizabeth R Mann

    doi:10.1101/2020.10.10.20207449 Date: 2020-10-16 Source: medRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD resulting in the clinical syndrome COVID-19 MESHD is associated with an exaggerated immune response and monocyte infiltrates in the lungs and other peripheral tissues. It is now increasingly recognised that chronic morbidity persists in some patients. We recently demonstrated profound alterations of monocytes in hospitalised COVID-19 MESHD patients. It is currently unclear whether these abnormalities resolve or progress following patient discharge. We show here that blood monocytes in convalescent patients at their 12 week follow up, have a greater propensity to produce pro-inflammatory cytokines TNF HGNC and IL-6 HGNC, which was consistently higher in patients with resolution of lung injury MESHD as indicated by a normal chest X-ray and no shortness of breath MESHD (a key symptom of lung injury MESHD). Furthermore, monocytes from convalescent patients also displayed enhanced levels of molecules involved in leucocyte migration, including chemokine receptor CXCR6 HGNC, adhesion molecule CD31 HGNC/PECAM and integrins VLA-4 and LFA-1 HGNC. Expression of migration molecules on monocytes was also consistently higher in convalescent patients with a normal chest X-ray. These data suggest persistent changes in innate immune function following recovery from COVID-19 MESHD and indicate that immune modulating therapies targeting monocytes and leucocyte migration may be useful in recovering COVID-19 MESHD patients with persistent symptoms.

    sMAdCAM:IL-6 (sMIL Index): A novel signature associated with COVID-19 MESHD disease progression and development of anti-SARS-CoV-2 antibodies

    Authors: Dhanashree Jagtap; Vikrant M Bhor; Shilpa Bhowmick; Nandini Kasarpalkar; Pooja Sagvekar; Bhalchandra Kulkarni; Manish Pathak; Nirjhar Chatterjee; Pranam Dolas; Harsha Palav; Snehal Kaginkar; Sharad Bhagat; Itti Munshi; Swapneil Parikh; Sachee Agrawal; Chandrakant Pawar; Mala Kaneria; Smita Mahale; Jayanthi Shastri; Vainav Patel

    doi:10.1101/2020.10.13.20182949 Date: 2020-10-16 Source: medRxiv

    IMPORTANCE: Recent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection MESHD highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19 MESHD. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. OBJECTIVE: To evaluate the role of systemic and gut inflammatory markers in disease progression and development of anti-viral humoral immunity following SARS-CoV-2 infection MESHD. DESIGN, SETTING AND PARTICIPANTS: This cohort study (n=58) of SARS-CoV-2 infected MESHD individuals included a group of in-patients (n=36) at various stages of disease progression together with convalescent individuals (n=22) recruited between April and June 2020 (peak of the epidemic) from a tertiary care hospital in Mumbai, India. Follow-up of 11 in-patients at day 7 post diagnosis was carried out, resulting in a total of 47 in-patient samples. EXPOSURES: Diagnosis of SARS-CoV-2 infections MESHD was confirmed by reverse transcriptase-polymerase chain reaction-based testing of nasopharyngeal/oropharyngeal samples. MAIN OUTCOMES AND MEASURES: Primary outcomes were the measurement of inflammatory markers including Th1 HGNC/Th2/Th17 cytokines and levels of soluble mucosal addressin cell adhesion molecule (sMAdCAM) in plasma. Anti-viral humoral response was measured by rapid antibody test (IgG, IgM) and chemiluminescent immunoassay (CLIA) (IgG). Also antibodies binding to SARS-CoV-2 proteins were measured by surface plasmon resonance ( SPR HGNC). Secondary outcomes were correlation of the inflammatory signature with clinical information, including age, sex, disease duration and co-morbidities. RESULTS: Twenty eight of 36 (78%) in-patients and 19 of 22 (86%) convalescents were males. Out of 47 in-patient samples, 22 (46%), 11 (23%) and 14 (30%) were IgG-/IgM-, IgG+/IgM+ and IgG+/IgM- respectively. Of 22 convalescent samples, 3 (14%), 1 (4%) and 17 (77%) were respectively IgG-/IgM-, IgG+/IgM+ and IgG+/IgM-. Two out of 22 (9%) convalescents showed high IL-6 HGNC levels (>100pg/ml) and 4 (18%) had high TNF HGNC levels (>30pg/ml). However, the convalescents (n =22) had significantly lower levels of IL-6 HGNC [Median=27.48 (IQR=23.54-39.92)] compared to followed up in-patients (n = 11) at day 0 [Median=111(IQR=68-129.7), p =0.0002] and higher levels of sMAdCAM [Median=1940 (1711-2174) pg/ml] compared to these individuals at day 0 [Median=1701 (IQR=1532-1836) pg/ml; p=0.032] and day 7 [Median=1534 (IQR=1236-1654) pg/ml; p=0.0007]. Further, IL-6 HGNC and sMAdCAM levels among in-patients inversely correlated with one another (r =-0.374, p = 0.009, CI = 95%). When expressed as a novel integrated marker, sMIL (sMAdCAM/ IL-6 HGNC ratio) index, these levels were incrementally and significantly higher across various disease states with convalescents exhibiting the highest values [Median= 64.74 (IQR=47.33-85.58)]. Also, the sMIL index was significantly higher in convalescents (with class-switched responses) compared to IgG+/IgM+ individuals at early stages of infection [Median=28.65 (IQR=13.63-96.26), p = 0.034]. Real-time measurement by SPR HGNC of plasma antibody binding to viral nucleocapsid (NC), receptor binding domain (RBD) and spike (S) revealed waxing and waning of plasma antibody responses to all 3 targets. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of RBD-binding (r = 0.462, p = 0.03, CI = 95%) and fold change in binding to S (r = 0.68, p = 0.050, CI = 95%) respectively. CONCLUSION AND RELEVANCE: Our results highlight key systemic and gut-associated immune parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19 MESHD.

    Clinical and molecular characteristics of COVID-19 MESHD patients with persistent SARS-CoV-2 infection MESHD

    Authors: Chaoyang Sun; Junpeng Fan; Jia Huang; Ensong Guo; Yu Fu; Si Liu; Rourou Xiao; Chen Liu; Funian Lu; Tianyu Qin; Chao He; Zizhuo Wang; Xu Qin; Dianxing Hu; Lixin You; Xi Li; Tian Wang; Peng Wu; Gang Chen; Jianfeng Zhou; Kezhen Li

    doi:10.21203/rs.3.rs-86940/v1 Date: 2020-10-02 Source: ResearchSquare

    The clinical features, molecular characteristics, and immune responses of COVID-19 MESHD patients with persistent SARS-CoV-2 infection MESHD are not yet well described. In this study, we investigated the differences in clinical parameters, laboratory indexes, plasma cytokines, and peripheral blood mononuclear cell responses, which were assessed using single-cell RNA-sequencing in patients with non-critical COVID-19 MESHD with long durations (LDs) and short durations (SDs) of viral shedding. Our results revealed that clinical parameters and laboratory indexes, such as c-reactive protein (CRP) HGNC and D-dimer, were comparable between SDs and LDs. Most inflammatory cytokines/chemokines, such as IL-2 HGNC, IL2R HGNC, TNFα HGNC/β, IL1β HGNC, and CCL5 HGNC were present at low levels in LDs. Our single-cell RNA-sequencing revealed a reconfiguration of the peripheral immune cell phenotype in LDs, including decreases in natural killer (NK) cells and CD14+ monocytes and an increase in regulatory T cells (Tregs). Furthermore, most cell subsets in LDs consistently exhibited reduced expression of ribosomal protein (RP) genes, indicating dysfunctions in cytokine/chemokine synthesis, folding, modification, and assembly. Accordingly, the negative correlation between the RP levels and viral shedding duration was validated in an independent cohort of bulk-RNA-sequencing data from 103 non-critical patients, which may help guide clinical management and resource allocation. Moreover, peripheral T and NK cells and memory B cells in LDs likely failed to activate, which contributed to the persistence of viral shedding.

    LMWF5A suppresses cytokine release by modulating select inflammatory transcription factor activity in stimulated PBMC

    Authors: Gregory Thomas; Elizabeth Frederick; Lisa Thompson; Raphael Bar-Or; Yetti Mulugeta; Melissa Hausburg; Michael Roshon; Charles Mains; David Bar-Or

    doi:10.21203/rs.3.rs-86515/v1 Date: 2020-10-01 Source: ResearchSquare

    Background Dysregulation of transcription and cytokine expression has been implicated in the pathogenesis of a variety inflammatory diseases. The resulting imbalance between inflammatory and resolving transcriptional programs can cause an overabundance of pro-inflammatory, classically activated macrophage type 1 (M1) and/or helper T cell type 1 ( Th1 HGNC) products, such as IFNγ HGNC, TNFα HGNC, IL1-β HGNC, and IL12, that prevent immune switching to resolution and healing. The low molecular weight fraction of human serum albumin (LMWF5A) is novel biologic drug that is currently under clinical investigation for the treatment of osteoarthritis MESHD and the hyper-inflammatory response associated with COVID-19 MESHD. This study aims to elucidate transcriptional mechanisms of action involved with the ability of LMWF5A to reduce pro-inflammatory cytokine release. Methods ELISA arrays were used to identify cytokines and chemokines influenced by LMWF5A treatment of LPS-stimulated peripheral blood mononuclear cells (PBMC). The resulting profiles were analyzed by gene enrichment to gain mechanistic insight into the biologic processes and transcription factors (TFs) underlying the identified differentially expressed cytokines. DNA-binding ELISAs, luciferase reporter assays, and TNFα HGNC or IL-1β HGNC relative potency were then employed to confirm the involvement of enriched pathways and TFs.Results LMWF5A was found to significantly inhibit a distinct set of pro-inflammatory cytokines ( TNFα HGNC, IL-1β HGNC, IL-12, CXCL9 HGNC, CXCL10 HGNC, and CXCL11 HGNC) associated with pro-inflammatory M1/ Th1 HGNC immune profiles. Gene enrichment analysis also suggests these cytokines are, in part, regulated by NF-κB and STAT transcription factors. Data from DNA-binding and reporter assays support this with LMWF5A inhibition of STAT1α DNA-binding activity as well as a reduction in overall NF-κB-driven luciferase expression. Experiments using antagonists specific for the immunomodulatory and NF-κB/STAT-repressing transcription factors, peroxisome proliferator-activated receptor ( PPAR)γ HGNC and aryl hydrocarbon receptor HGNC ( AhR HGNC), indicate these pathways are involved in the LMWF5A mechanism of action by reducing LMWF5A drug potency as measured by TNFα HGNC and IL-1β HGNC release. Conclusion In this report, we provide evidence that LMWF5A reduces pro-inflammatory cytokine release by activating the immunoregulatory transcription factors PPARγ HGNC and AhR HGNC. In addition, our data indicate that LMWF5A suppresses NF-κB and STAT1α pro-inflammatory pathways. This suggests that LMWF5A act through these mechanisms to decrease pro-inflammatory transcription factor activity and subsequent inflammatory cytokine production.

    Dynamic changes in serum IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC are associated with the outcome of patients with severe COVID-19 MESHD in ICU

    Authors: Jia Li; Liu Rong; Ran Cui; Jiaqi Feng; Yuyang Jin; Yuetian Yu; Xiaoxiang Chen; Renying Xu

    doi:10.21203/rs.3.rs-83336/v1 Date: 2020-09-25 Source: ResearchSquare

    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.

    Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection

    Authors: Jessica Graham; Jessica Swarts; Sarah R Leist; Alexandra Schafer; Vineet D Menachery; Lisa Gralinski; Sophia Jeng; Darla R Miller; Michael Mooney; Shannon McWeeney; Martin T. Ferris; Fernando Pardo-Manuel de Villena; Mark T. Heise; Ralph S. Baric; Jennifer M Lund; Laura Huckins; Benjamin tenOever; Schahram Akbarian; Kristen J Brennand; Katherine H Hullsiek; David R Boulware; SARAH M LOFGREN; Martirene A da Silva; Brian Custer; Manoel Barral-Netto; Moritz Kraemer; Rafael HM Pererira; Oliver G Pybus; Michael P Busch; Márcia C Castro; Christopher Dye; Vitor H Nascimento; Nuno R Faria; Ester C Sabino

    doi:10.1101/2020.09.21.306837 Date: 2020-09-21 Source: bioRxiv

    The COVID-19 MESHD COVID-19 MESHD pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV MESHD to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection MESHD of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 HGNC and CD8 HGNC T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg HGNC and IL17 HGNC over TNFa HGNC also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV MESHD serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection MESHD. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.

    LOX-1 HGNC+ immature neutrophils predict severe COVID-19 MESHD patients at risk of thrombotic complications

    Authors: Behazine Combadiere; Lucille Adam; Paul Quentric; Pierre Rosenbaum; Karim Dorgham; Olivia Bonduelle; Christophe Parizot; Delphine Sauce; Julien Mayaux; Charles-Edouard Luyt; Alexandre Boissonnas; Zahir Amoura; Valerie Pourcher; Makoto Miyara; Guy Gorochov; Amelie Guihot; Christophe Combadiere; Duraipandian Thavaselvam; Devendra Kumar Dubey; Paul Lin; Hila Shaim; Sean G Yates; David Marin; Indreshpal Kaur; Sheetal Rao; Duncan Mak; Angelique Lin; Qi Miao; Jinzhuang Dou; Ken Chen; Richard Champlin; Elizabeth J Shpall; Katayoun Rezvani

    doi:10.1101/2020.09.15.293100 Date: 2020-09-15 Source: bioRxiv

    Rational: Lymphopenia MESHD and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease 2019 MESHD ( COVID-19 MESHD) severity. Objective: We sought to investigate the representation of neutrophil subsets in severe and critical COVID-19 MESHD patients based on Intensive Care Units (ICU) and non-ICU admission. Methods: We developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 MESHD phenotypes in critical and severe patients. Results: Our results showed that 80 percent of ICU patients develop strong myelemia with CD10 HGNC- CD64 HGNC+ immature neutrophils. Cellular profiling revealed two distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 ( LOX-1 HGNC) or the Interleukin-3 receptor alpha ( CD123 HGNC), both significantly overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1 HGNC-expressing immature neutrophils positively correlated with clinical severity, with the cytokine storm ( IL-1{beta HGNC}, IL-6 HGNC, IL-8 HGNC, TNF HGNC), and with intravascular coagulation MESHD. Importantly, high proportions of LOX-1 HGNC+-immature neutrophils are associated with high risks of severe thrombosis MESHD. Conclusions: Together these data suggest that point of care enumeration of LOX-1 HGNC-immature neutrophils might help distinguish patients at risk of thrombosis MESHD complication and most likely to benefit from intensified anticoagulant therapy.

    COVID-19 MESHD Biomarkers in research: Extension of the OncoMX cancer biomarker data model to capture biomarker data from other diseases.

    Authors: Nikhita Gogate; Daniel Lyman; Keith A Crandall; Robel Kahsay; Darren A. Natale; Sabyasachi Sen; Raja Mazumder; Tongqing Zhou; Shilei Ding; Romain Gasser; Jeremie Prevost; Guillaume Beaudoin-Bussieres; Sai Priya Anand; Annemarie Laumaea; Jonathan R. Grover; Liu Lihong; David D Ho; John Mascola; Andres Finzi; Peter D. Kwong; Walther Mothes

    doi:10.1101/2020.09.09.196220 Date: 2020-09-10 Source: bioRxiv

    Scientists, medical researchers, and health care workers have mobilized worldwide in response to the outbreak of COVID-19 MESHD, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; SCoV2). Preliminary data have captured a wide range of host responses, symptoms, and lingering problems post-recovery within the human population. These variable clinical manifestations suggest differences in influential factors, such as innate and adaptive host immunity, existing or underlying health conditions, co-morbidities, genetics, and other factors. As COVID-19 MESHD-related data continue to accumulate from disparate groups, the heterogeneous nature of these datasets poses challenges for efficient extrapolation of meaningful observations, hindering translation of information into clinical applications. Attempts to utilize, analyze, or combine biomarker datasets from multiple sources have shown to be inefficient and complicated, without a unifying resource. As such, there is an urgent need within the research community for the rapid development of an integrated and harmonized COVID-19 MESHD Biomarker Knowledgebase. By leveraging data collection and integration methods, backed by a robust data model developed to capture cancer MESHD biomarker data we have rapidly crowdsourced the collection and harmonization of COVID-19 MESHD biomarkers. Our resource currently has 138 unique biomarkers. We found multiple instances of the same biomarker substance being suggested as multiple biomarker types during our extensive cross-validation and manual curation. As a result, our Knowledgebase currently has 265 biomarker type combinations. Every biomarker entry is made comprehensive by bringing in together ancillary data from multiple sources such as biomarker accessions (canonical UniProtKB accession, PubChem Compound ID, Cell Ontology ID, Protein Ontology ID, NCI Thesaurus Code, and Disease Ontology ID), BEST biomarker category, and specimen type (Uberon Anatomy Ontology) unified with ontology standards. Our preliminary observations show distinct trends in the collated biomarkers. Most biomarkers are related to the immune system (SAA, TNF HGNC-{propto}, and IP-10 HGNC) or coagulopathies MESHD (D-dimer, antithrombin HGNC, and VWF HGNC) and a few have already been established as cancer MESHD biomarkers ( ACE2 HGNC, IL-6 HGNC, IL-4 HGNC and IL-2 HGNC). These trends align with proposed hypotheses of clinical manifestations compounding the complexity of COVID-19 MESHD pathobiology. We explore these trends as we put forth a COVID-19 MESHD biomarker resource that will help researchers and diagnosticians alike. All biomarker data are freely available from https://data.oncomx.org/ covid19 MESHD.

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HGNC Genes
SARS-CoV-2 Proteins


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