preVIEW: COVID-19

Corpus overview

Overview

MeSH Disease

COVID-19 (127)

Inflammation (32)

Severe Acute Respiratory Syndrome (27)

Necrosis (21)

Coronavirus Infections (17)


HGNC Genes

tumor necrosis factor (134)

interleukin 6 (81)

interleukin 10 (28)

C-X-C motif chemokine ligand 8 (25)

interferon gamma (25)


SARS-CoV-2 proteins

ProteinS (14)

NSP5 (4)

ProteinS1 (3)

ProteinN (2)

NSP2 (1)


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    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.

    Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology

    Authors: Andrew H Karaba; Weiqiang Zhou; Leon L Hsieh; Alexis Figueroa; Guido Massaccesi; Richard E Rothman; Katherine ZJ Fenstermacher; Lauren Sauer; Kathryn Shaw-Saliba; Paul W Blair; Sherry Leung; Russell Wesson; Nada Alachkar; Ramy El-Diwany; Hongkai Ji; Andrea L Cox

    doi:10.1101/2021.01.29.21250317 Date: 2021-02-01 Source: medRxiv

    Background: Several inflammatory cytokines are upregulated in severe COVID-19 MESHD. We compared cytokines in COVID-19 MESHD versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19 MESHD, we examined the relationship of BMI to cytokines associated with severe disease. Methods: Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19 MESHD, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 MESHD and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity. Results: IL-18 HGNC, IL-1{beta HGNC}, IL-6 HGNC, and TNF HGNC- were significantly increased in COVID-19 MESHD versus influenza patients while GM-CSF HGNC, IFN-{gamma}, IFN-{lambda}1, IL-10 HGNC, IL-15 HGNC, and MCP-2 HGNC were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18 HGNC, IL-6 HGNC, and TNF HGNC- were elevated in severe COVID-19 MESHD, but not severe influenza. Random forest analysis identified high IL-6 HGNC and low IFN-{lambda}1 HGNC levels as the most distinct between severe COVID-19 MESHD and severe influenza. Finally, IL-1RA HGNC was identified as a potential mediator of the effects of BMI on COVID-19 MESHD severity. Conclusions: These findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection MESHD, and emphasize drivers of severe COVID-19 MESHD to focus both mechanistic and therapeutic investigations.

    The Significance of KL-6 HGNC as Prognosis Monitoring Biomarker in Patients With Severe COVID-19 MESHD From Stabilized Stage Toward Convalescence

    Authors: Long He; Liu Lu; Ming Zong; Huang Zhou; Lan Wang; Nian Zhen Chen; Jia Yi Yuan; Er Peng Jiang; Liang Zheng; Qiang Li; Lie Ying Fan; Zhong Min Liu

    doi:10.21203/rs.3.rs-191056/v1 Date: 2021-01-30 Source: ResearchSquare

    Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury MESHD in severe COVID-19 MESHD patients from stabilized stage toward convalescence.Methods: We enrolled participants who diagnosed with severe COVID-19 MESHD (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines ( IL-1β HGNC, IL-2 HGNC, IL-4 HGNC, IL-5 HGNC, IL-6 HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC, TNF-α HGNC, IFN-α, IFN-γ HGNC), type II alveolar epithelium injury MESHD indicators ( Surfactant protein A HGNC ( SP-A HGNC), Krebs von den Lungen-6 HGNC von MESHD den Lungen-6 ( KL-6 HGNC)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: In stabilized stage, the parameters of blood routine and some cytokines ( IL-1β HGNC, IL-2 HGNC, IL-4 HGNC, IL-12p70, TNF-α HGNC) had bounced back to normal (p>0.05). Some cytokines ( IL-5 HGNC, IL-6 HGNC, IL-10 HGNC, IL-17A HGNC, IFN-α, IFN-γ HGNC) and type II alveolar epithelium injury MESHD indicators ( SP-A HGNC and KL-6 HGNC) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5 HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC,  IFN-γ HGNC, IFN-α, SP-A HGNC and KL-6 HGNC were downward trend (p<0.05), only KL-6 HGNC level (p<0.05) could simultaneously reflect the lung injury MESHD volume which be measured by CT. Conclusions: Our preliminary data indicated that KL-6 HGNC could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 MESHD from stabilized stage toward convalescence.

    Identification of Serum Prognostic Biomarkers of Severe  COVID-19 MESHD by Quantitative Proteomic Approach

    Authors: Yayoi Kimura; Yusuke Nakai; Jihey Shin; Miyui Hara; Yuriko Takeda; Sousuke Kubo; Sundararaj S Jeremiah; Yoko Ino; Tomoko Akiyama; Kayano Moriyama; Kazuya Sakai; Ryo Saji; Mototsugu Nishii; Hideya Kitamura; Kota Murohashi; Kouji Yamamoto; Takeshi Kaneko; Ichiro Takeuchi; Eri Hagiwara; Takashi Ogura; Hideki Hasegawa; Tomohiko Tamura; Takeharu Yamanaka; Akihide Ryo

    doi:10.21203/rs.3.rs-156575/v1 Date: 2021-01-27 Source: ResearchSquare

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

    Patients with Asthma and Chronic Obstructive Pulmonary Disease MESHD ( COPD MESHD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19 MESHD

    Authors: Nathalie Acevedo; Jose Miguel Escamilla-Gil; Hector Espinoza; Ronald Regino; Jonathan Ramirez; Lucila Florez De Arco; Rodolfo Dennis; Carlos Torres-Duque; Luis Caraballo

    doi:10.1101/2021.01.23.21250370 Date: 2021-01-26 Source: medRxiv

    BackgroundChronic obstructive pulmonary disease MESHD ( COPD MESHD) is associated with increased risk of severe COVID-19 MESHD, but the mechanisms are unclear. Besides, patients with severe COVID-19 MESHD have been reported to have increased levels of several immune mediators. ObjectiveTo perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma MESHD and COPD and to evaluate their relationship with biomarkers of severe COVID-19 MESHD. MethodsNinety-two proteins were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic MESHD. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection MESHD reported in the " COVID-19 MESHD Drug and Gene Set Library" and with known protein biomarkers of severe COVID-19 MESHD. ResultsForty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 HGNC while COPD patients have a broader systemic inflammatory dysregulation driven by HGF HGNC, OPG HGNC, and several chemokines ( CXCL9 HGNC, CXCL10 HGNC, CXCL11 HGNC, CX3CL1 HGNC, CXCL1 HGNC, MCP-3 HGNC, MCP-4 HGNC, CCL3 HGNC, CCL4 HGNC and CCL11 HGNC). These proteins are involved in chemokine signaling pathways related with response to viral infections MESHD and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 MESHD Related Gene Sets database. An increase of HPG, CXCL9 HGNC, CXCL10 HGNC, IL-6 HGNC, MCP-3 HGNC, TNF HGNC and EN-RAGE HGNC has also been found in patients with severe COVID-19 MESHD. ConclusionsCOPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19 MESHD. Our study suggests that COPD patients have a systemic dysregulation MESHD in chemokine networks (including HGF HGNC and CXCL9 HGNC) that could make them more susceptible to severe COVID-19 MESHD. Our study also suggest that IL-6 HGNC levels are increased in some asthmatics and this may influence their immune response to COVID-19 MESHD.

    Network Representation Learning-Based Drug Mechanism Discovery and Anti-Inflammatory Response Against COVID-19 MESHD

    Authors: Wang Xiaoqi; Bin Xin; Zhijian Xu; Kenli LI; Fei Li; Wu Zhong; Weihong Tan; Shaoliang Peng

    doi:10.26434/chemrxiv.12531314.v3 Date: 2021-01-18 Source: ChemRxiv

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

    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.

    Efficacy of Doxycycline in treating COVID-19 MESHD Positive Patients: A Case Series

    Authors: Zohreh Akhoundi Meybody; Mohammad Bagher Owlia; Sina Owlia; Seyed Rohollah Mousavinasab

    doi:10.21203/rs.3.rs-141875/v3 Date: 2021-01-06 Source: ResearchSquare

    Background: Given the high morbidity and mortality caused by Coronavirus Disease 2019 MESHD ( COVID-19 MESHD), scientific research is necessary to achieve a proper treatment regimen. Since doxycycline is effective in reducing inflammatory factors, including IL-6 HGNC and TNF-alpha HGNC that play an important role in initiating cytokine storms and probably causing death MESHD in patients with COVID-19 MESHD, its use is associated with low side effects and can be used orally, the present study was attempted to evaluate the efficacy of doxycycline in the treatment of inpatients and outpatients with COVID-19 MESHD.Methods: This descriptive and prospective study was performed on inpatients and outpatients were diagnosed with COVID-19 MESHD based on polymerase chain reaction (PCR) test from nasopharyngeal secretions or computerized tomography scan (CT Scan). Patients who met the inclusion criteria received doxycycline at a dose of 100 mg every 12 hours for 7 days and then were evaluated on the baseline day and on days 3, 7, and 14 after admission for cough, Shortness of breath MESHD, temperature and oxygen saturation.Results:  Out of 21 patients, 11 patients were male and 10 patients were female. Cough, SOB, temperature, and O2 sat improved in both of outpatients and inpatients compared to baseline. In general, the results showed that doxycycline was more effective in improving cough, SOB, temperature, and O2 sat in outpatients than inpatients. Conclusion:  It can be concluded that doxycycline with the dose and duration prescribed in our study could play an effective role in the treatment of patients with COVID-19 MESHD. 

    Humoral and cell-mediated response in colostrum after exposure to severe acute respiratory syndrome coronavirus 2 MESHD

    Authors: Vignesh Narayanaswamy; Brian Pentecost; Dominique Alfandari; Emily Chin; Kathleen Minor; Alyssa Kastrinakis; Tanya Lieberman; Kathleen F Arcaro; Heidi Leftwich

    doi:10.1101/2021.01.03.20248715 Date: 2021-01-04 Source: medRxiv

    BackgroundColostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum. ObjectiveTo evaluate the presence of antibodies specific to SARS-CoV-2 and the associated cytokines in colostrum from women who tested positive for the virus. Study DesignBetween March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Five of these 15 COVID-19 MESHD positive women also provided bilateral liquid colostrum within 1-2 days of providing the spot card samples. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre- COVID-19 MESHD controls. All samples were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike PROTEIN protein using an ELISA that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM, and for concentrations of 10 inflammatory cytokines ( IFN{gamma HGNC}, TNF HGNC, IL-1{beta HGNC}, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-12, IL-13 HGNC) using a multiplex electrochemiluminescent sandwich assay. ResultsBilateral colostrum samples from 73%, 73% and 33% of the 15 COVID-19 MESHD mothers exhibited IgA, IgG, and IgM reactivity to RBD respectively. Colostrum samples from two of the 8 pre-pandemic controls showed IgA and IgG reactivity to RBD. Additionally, COVID-19 MESHD mothers had significantly higher levels of 9 of the 10 inflammatory markers (all except IFN{gamma HGNC}) as compared to the pre- COVID-19 MESHD controls. Comparable results were obtained with both the spot card-eluates and liquid samples. ConclusionsA strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. High levels of 9 inflammatory markers were also present in the colostrum. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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