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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (14)

ProteinN (5)

NSP5 (4)

NSP3 (2)

ProteinS1 (2)


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    Effect of COVID-19 MESHD on Lipid Profile and its Correlation with Acute Phase Reactants

    Authors: Jahanzeb Malik; Uzma Ishaq; Talha Laique; Amna Ashraf; Asmara Malik; Mommana Ali Rathore; Syed Muhammad Jawad Zaidi; Muhammad Javaid; Asad Mehmood

    doi:10.1101/2021.04.13.21255142 Date: 2021-04-14 Source: medRxiv

    Background and Objective Coronavirus disease 2019 MESHD ( COVID-19 MESHD) manifests as multiple clinical and pathological organ dysfunctions. It also disrupts metabolic profile due to the release of pro-inflammatory cytokines causing a systemic inflammation reaction MESHD. However, the development and correlation of dyslipidemia MESHD with acute phase reactants is unknown. This investigation was performed to assess the pathological alterations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL), triglycerides, and total cholesterol levels in COVID-19 MESHD patients. Methods This was a prospective study performed on real-world patients to assess serum levels of LDL-C, HDL, TG, TC on COVID-19 MESHD patients (mild: 319; moderate: 391; critical: 357) hospitalized at our center between April 2020 through January 2021. Age- and gender-matched controls who had their lipid profiles in the same period were included as the control group. Results LDL-C, HDL, TG, and TC levels were significantly lower in COVID-19 MESHD patients when compared with the control group (P < 0.001, 0.047, 0.045, < 0.001, respectively). All parameters decreased gradually with COVID-19 MESHD disease severity (LDL-C: median (IQR), mild: 98 (91,134); moderate: 97 (81,113); critical: 68 (68,83); HDL: mild: 45 (37,50); moderate: 46 (41,50); critical: 40 (37,46); TG: mild: 186 (150,245); moderate: 156 (109,198); critical: 111 (98,154); TC: mild: 224 (212,238); moderate: 212 (203,213); critical: 154 (125,187)). LDL-C, TC, and TG were inversely correlated with acute phase reactants ( interleukin-6 HGNC ( IL-6 HGNC), Procalcitonin, C-reactive protein HGNC ( CRP HGNC), and D-dimers). Logistic regression demonstrated lipid profile, thyroid profile, and acute phase reactants as predictors of severity of COVID-19 MESHD disease. Conclusion Hypolipidemia MESHD develops in increasing frequency with severe COVID-19 MESHD disease. It inversely correlates with levels of acute-phase reactants, indicating SARS-COV-2 as the causative agent for alteration in lipid and thyroid levels.

    Elevated anti-SARS-CoV-2 antibodies and IL-6 HGNC, IL-8 HGNC, MIP-1β HGNC, early predictors of severe COVID-19 MESHD.

    Authors: Helena Codina; Irene Vieitez; Alicia Gutierrez-Valencia; Vasso Skouridou; Cristina Mart&iacutenez; Luc&iacutea Pati&ntildeo; Mariluz Botero-Gallego; Mar&iacutea Trujillo-Rodr&iacuteguez; Ana Serna-Gallego; Esperanza Mu&ntildeoz-Muela; Mar&iacutea M. Bobillo; Alexandre P&eacuterez; Jorge Julio Cabrera-Alvar; Manuel Crespo; Ezequiel Ruiz-Mateos; Eva Poveda

    doi:10.1101/2021.04.13.439586 Date: 2021-04-13 Source: bioRxiv

    Background: Viral and host immune kinetics during acute COVID-19 MESHD and after remission of acute symptoms need better characterization. Methods: SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and pro-inflammatory cytokines were measured in sequential samples among hospitalized COVID-19 MESHD patients during acute infection MESHD and 6 months following diagnosis. Results: 24 laboratory-confirmed COVID-19 MESHD patients with mild/moderate and severe COVID-19 MESHD were included. Most were males 83%, median age of 61 years. 21% were admitted to the ICU and 8 of them (33.3%) met criteria for severe COVID-19 MESHD disease. A delay in SARS-CoV-2 levels decline during the first 6 days of follow-up and viral load persistence until month 3 were related with severe COVID-19 MESHD, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6 HGNC, IL-8 HGNC and MIP-1{beta HGNC} at the diagnosis time were related with severe COVID-19 MESHD outcome. Higher levels of MIP-1{beta} HGNC, IL-1{beta} HGNC, MIP-1 HGNC and IFN-{gamma HGNC} were observed at month 1-3 during mild/moderate disease compared to severe COVID-19 MESHD. IgG persisted at low levels after 6 months of diagnosis. Conclusions: Higher concentrations of IgA, IgM, and IgG, and IL-6 HGNC, IL-8 HGNC and MIP-1{beta HGNC} are identified as early predictors of COVID-19 MESHD severity, but not SARS-CoV-2 RNA levels at diagnosis.

    Clinical Characteristics and Outcomes of Critically ill Mechanically Ventilated MESHD COVID-19 MESHD Patients Receiving interleukin-6 HGNC Receptor Antagonists and/or Corticosteroid Therapy, the INTERACT study: A Multicenter International Observational Study

    Authors: Marwa R Amer; Mohammed Bawazeer; Khalid Maghrabi; Ahmed Mohamed Kamal; Abid Butt; Talal Dahhan; Eiad Kseibi; Mohammed Abujazar; Razan Alghunaim; Muath Rabee; Maal Abualkhair; Ali Al-Janoubi; Abeer AlFirm; Syed Moazzum Khurshid; Ognjen Gajic; Allan J. Walkey; Jarrod M Mosier; Igor Borisovich Zabolotskikh; Oscar Y Gavidia; Santiago Y. Teruel; Michael A. Bernstein; Karen Boman; Vishakha K. Kumar; Vikas Bansal; Rahul Kashyap

    doi:10.1101/2021.04.12.21255323 Date: 2021-04-13 Source: medRxiv

    Objectives: To compare the clinical characteristics and outcomes of critically ill coronavirus disease MESHD ( COVID-19 MESHD) patients requiring mechanical ventilation (MV), receiving interleukin 6 receptor ( IL6R HGNC) antagonists, steroids, or a combination of both. Design: An international, multicenter, observational study derived from the COVID-2019 Viral Infection and Respiratory Illness University Study (VIRUS) registry and conducted through the Discovery Network, the Society of Critical Care Medicine. Marginal structural modeling was used to adjust for time-dependent confounders, and observations were weighted using the inverse probability of treatment weight. Sensitivity analysis was conducted to emulate a target trial design. Setting: 168 hospitals in 16 countries. Patients: adult ICU patients ( > 18 years) requiring MV for COVID-19 MESHD between March 01, 2020, and January 10, 2021. Intervention: None. Measurements and Main Results: A total of 860 patients met eligibility criteria: 589 received steroids, 170 IL-6R HGNC antagonists, and 101 combination therapy, and the groups were balanced after adjustment. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (IQR: 6 to 14 mg); 80.8% received low-dose and 19.2% high-dose steroids (> 15 mg/day of dexamethasone or equivalent). The median C-reactive protein HGNC level was > 75 mg/L in majority of our cohort. The use of IL6R HGNC antagonists alone or in combination was not associated with a significant difference in ventilator free days ( VFD MESHD) compared to steroids alone (adjusted incidence rate ratio [95% CI]): IL6R HGNC antagonists (1.12 [0.88,1.4]), combination (0.83 [0.6,1.14]). Patients treated with low or high-dose steroids had non-significant differences in VFD MESHD compared to IL6R HGNC antagonists (beta= 0.62, 95% CI -1.54, 2.78 for low-dose steroid; beta= -1.19, 95% CI -3.85, 1.47 for high-dose steroid). The use of IL6R HGNC antagonists alone or in combination was not associated with a significant difference in 28 day mortality compared to steroids alone (adjusted odds ratio [95% CI]): IL6R HGNC antagonists alone (0.68 [0.44,1.07]), combination (1.07 [0.67,1.7]). There was no difference in hospital mortality compared to steroids alone (aOR 0.68, 95% CI 0.43,1.09 for IL6R HGNC antagonist, aOR 1.23, 95 % CI 0.72,2.11 for combination). The findings of sensitivity analysis were consistent with the primary analysis. The rate of liver dysfunction MESHD was higher in the IL6R HGNC antagonist (p=0.038), while the rate of bacteremia MESHD did not differ among the three groups. Conclusions: We observed no difference in outcomes between mechanically ventilated adult ICU patients who received IL6R HGNC antagonists, steroids, or combination therapy and those who received IL6R HGNC antagonists or low or high dose steroids. Further trials are needed to evaluate high-dose steroids as substitutes for IL6R HGNC antagonists in resource-limited settings.

    SARS-CoV-2 infection MESHD in the Syrian hamster model causes inflammation MESHD as well as type I interferon dysregulation MESHD in both respiratory and non-respiratory tissues including the heart and kidney

    Authors: Magen Francis; Una Goncin; Andrea Kroeker; Cynthia Swan; Robyn Ralph; Yao Lu; Athema Etzioni; Darryl Falzarano; Volker Gerdts; Steve Machtaler; Jason Kindrachuk; Alyson Ann Kelvin

    doi:10.1101/2021.04.07.438843 Date: 2021-04-08 Source: bioRxiv

    COVID-19 MESHD ( coronavirus disease 2019 MESHD) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection MESHD is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 MESHD as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection MESHD in Syrian hamsters. We found significant increases in inflammatory cytokines ( IL-6 HGNC, IL-1beta HGNC, and TNF HGNC) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation MESHD in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation MESHD. These results give insight into the multiorgan disease experienced by people with COVID-19 MESHD and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

    Human pulmonary artery endothelial cells upregulate ACE2 HGNC expression in response to iron-regulatory elements: potential implications for SARS-CoV-2 infection MESHD of vascular endothelial cells.

    Authors: Quezia K Toe; Theo Issitt; Abdul Mahomed; Ioannis Panselinas; Fatma Almaghlouth; Anne Burke-Gaffney; Stephen John Wort; Gregory J Quinlan

    doi:10.1101/2021.04.08.437687 Date: 2021-04-08 Source: bioRxiv

    Emerging studies from the ongoing covid-19 pandemic MESHD have implicated vascular dysfunction MESHD and endotheliitis MESHD in many patients presenting with severe disease. However, there is limited evidence for the expression of ACE2 HGNC (the principal co-receptor for Sars-Cov-2 cellular attachment) in vascular endothelial cells which has prompted the suggestion that the virus does not infect these cell types. However, the studies presented here demonstrate enhanced expression of ACE2 HGNC at the level of both mRNA and protein, in human pulmonary artery endothelial cells (PAECs) challenged with either IL-6 HGNC or hepcidin HGNC. Notably elevated levels both these iron-regulatory elements have been described in Covid-19 MESHD patients with severe disease and are further associated with morbidity and mortality. Additionally, levels of both IL-6 HGNC and hepcidin HGNC are often elevated in the elderly and in chronic disease MESHD settings, these populations being at greater risk of adverse outcomes from Sars-Cov-2 infection MESHD. A role for IL-6 HGNC and hepcidin HGNC as modulators of ACE2 HGNC expression seems plausible, additional, studies are required to determine if viral infection MESHD can be demonstrated in PAECs challenged with either of these iron-regulatory elements.

    Relative expression of pro-inflammatory molecules in COVID-19 MESHD patients manifested disease severities.

    Authors: Shireen Nigar; SM Tanjil Shah; Ali Ahasan Setu; Sourav Dutta Dip; Habiba Ibnat; M. Touhid Islam; Selina Akter; Iqbal Kabir Jahid; Md. Anwar Hossain

    doi:10.1101/2021.04.01.21254770 Date: 2021-04-07 Source: medRxiv

    Aggressive immune response, due to over-expressed pro-inflammatory molecules, had been characterized in COVID-19 MESHD patients. Some of those mediators have a dual and opposite role on immune-systems to play behind differential disease severities. We investigated the expression of some cytokines and chemokines in COVID-19 MESHD patients in Bangladesh. We diagnosed the patients by detecting SARS-CoV-2 RNA in nasal swab samples by the real-time RT-PCR method. Thirty adult patients were preselected based on their disease severities and grouped into mild, moderate, and severe cases. Nine healthy volunteers participated in this study as control. Relative expression of nine cytokines/chemokine in total leukocytes was semi-quantified in SYBRgreen-based qRT-PCR. We performed statistical tests on transformed log data using SPSS 24.0. At the onset of symptoms (day-1), ACE2 HGNC (P < 0.05) and IL-6 HGNC (P > 0.05) were up-regulated in all COVID-19 MESHD groups, although expression levels did not significantly correlate with disease severities. However, expression of IL-6 HGNC, MCP-1 HGNC, MIP-1 HGNC, TNF- HGNC, RANTES HGNC, and ACE2 HGNC, on day-14, were positively correlated with disease severities. Relative viral load at day-1 showed no significant correlation with cytokine expression but had a significant positive correlation with RANTES HGNC and ACE2 HGNC expression on day-14 (P < 0.05). Male patients had a higher level of IL-6 HGNC than female patients on day-1 (P < 0.05). All COVID-19 MESHD patients showed up-regulated cytokines and chemokines on the day-14 compared to day-1 except TNF HGNC-. Female patients had higher expression of ACE2 HGNC and IL-12 on day-14. Up-regulated cytokines/chemokines at the convalescent stage, especially IL-6 HGNC, may target anti-cytokine therapy in post- COVID-19 MESHD patients management.

    CERC-002, a human anti-LIGHT mAb reduces respiratory failure MESHD and death MESHD in hospitalized COVID-19 MESHD ARDS MESHD patients

    Authors: David S. Perlin; Garry A. Neil; Colleen Anderson; Inbal Zafir-Lavie; Lori Roadcap; Shane Raines; Carl Ware; Jeffrey Wilkins

    doi:10.1101/2021.04.03.21254748 Date: 2021-04-07 Source: medRxiv

    Background Severe COVID-19 MESHD infection is associated with dysregulated MESHD immune response which, in a substantial minority of patients, results in cytokine release syndrome ( CRS MESHD) and acute respiratory distress syndrome MESHD ( ARDS MESHD). Inhibition of cytokines or cytokine-associated signal transduction is a promising strategy to ameliorate ARDS MESHD associated with CRS. We and others have previously shown that serum free LIGHT ( TNFSF14 HGNC) levels are markedly elevated in patients with COVID-19 MESHD pneumonia MESHD/ARDS10,11, suggesting that LIGHT neutralization may offer therapeutic benefit to COVID-19 MESHD ARDS MESHD patients. Methods We conducted a randomized, double-blind, placebo-controlled, multi-center, proof-of-concept clinical trial of CERC-002 in adults with mild to moderate ARDS MESHD associated with COVID-19 MESHD (n=83). Enrolled patients received a single dose of CERC-002 or placebo, in addition to standard of care that included high dose corticosteroids. The primary efficacy endpoint was alive and free of respiratory failure MESHD status through Day 28. Secondary outcomes included alive status at Day 28, free of invasive ventilation through Day 28, and serum free LIGHT levels. Results In patients hospitalized with COVID-19 MESHD associated pneumonia MESHD and mild to moderate ( ARDS MESHD), CERC-002 increased the rate of alive and free of respiratory failure MESHD status through Day 28 as compared to placebo (83.9% vs 64.5%; p=0.044). Efficacy was highest in the prespecified subgroup of patients 60 years old and older (76.5% vs 47.1%; p=0.042), the population most vulnerable to severe complications and death MESHD with COVID-19 MESHD infection. Through both the initial 28-day and 60-day follow-up periods, reductions of approximately 50% in mortality were observed for CERC-002 compared to placebo (7.7% vs 14.3% at Day 28 and 10.8% vs 22.5% at Day 60). Importantly, this improvement was incremental to standard of care including high dose steroids and remdesivir 88.0% and 57.8%, respectively). In addition, serum LIGHT levels but not IL-6 HGNC levels were markedly reduced in patients treated with CERC-002. Conclusions The data presented herein demonstrate that CERC-002 markedly reduces the risk of respiratory failure MESHD and death incremental MESHD to standard of care including high dose corticosteroids and reduces LIGHT levels in patients with COVID-19 MESHD ARDS MESHD. (ClinicalTrials.gov number NCT04412057).

    Making sense of non-randomized comparative treatment studies in times of Covid-19 MESHD: A case study of tocilizumab

    Authors: Ruth R C Owen; Nawab Qizilbash; Sara Velazquez Diaz; Jose Maria Castellano Vazquez; Stuart J Pocock

    doi:10.1101/2021.04.06.21254612 Date: 2021-04-07 Source: medRxiv

    BACKGROUND Tocilizumab (TCZ) is an interleukin-6 HGNC inhibitor and the second established effective drug for the treatment of hospitalized patients with Covid-19 MESHD. In this study, we sought to validate the recent positive findings from the randomised clinical trial RECOVERY and to evaluate the challenges in the analysis and interpretation of non-randomized comparative effectiveness studies in Covid-19 MESHD. METHODS We performed a retrospective cohort study using an openly available database of hospitalised Covid-19 MESHD patients in Spain. The primary outcome was all-cause in-hospital mortality at 28 days. We used multivariable Fine and Gray competing risk models which adjusted for both fixed and time-variant confounders to investigate the effect of TCZ on the primary outcome. RESULTS We analysed 2547 patients hospitalised with Covid-19 MESHD between 1st January and 28th June 2020. Patients in the TCZ group tended to have more severe Covid-19 MESHD at admission, as measured by biomarkers of disease severity including CRP HGNC, D-dimer and LDH. At 28 days, 91 out of 440 TCZ patients had died compared to 267 out of 2107 patients in the control group. In multivariable analysis, there was no evidence of an association between TCZ and the primary outcome (adjusted hazard ratio 1.20, 95% CI 0.86 to 1.64, P=0.26). CONCLUSIONS Our observational study failed to find a benefit of TCZ on all-cause in-hospital mortality in Covid-19 MESHD patients compared with randomized trials, highlighting the impact that unmeasured confounding and other sources of bias can have in a retrospective observational setting. For future observational studies, we recommend prospective data collection to ensure all variables have the necessary quality, completeness and timing for reliable treatment evaluation.

    Predicting the severity of disease progression in COVID-19 MESHD at the individual and population level: A mathematical model

    Authors: Narendra Chirmule; Pradio Nair; Bela Desai; Ravindra Khare; Vivek R Nerurkar; Amitabh Gaur

    doi:10.1101/2021.04.01.21254804 Date: 2021-04-07 Source: medRxiv

    The impact of COVID-19 MESHD disease on health and economy has been global, and the magnitude of devastation is unparalleled in modern history. Any potential course of action to manage this complex disease requires the systematic and efficient analysis of data that can delineate the underlying pathogenesis. We have developed a mathematical model of disease progression to predict the clinical outcome, utilizing a set of causal factors known to contribute to COVID-19 MESHD pathology such as age, comorbidities, and certain viral and immunological parameters. Viral load and selected indicators of a dysfunctional MESHD immune response, such as cytokines IL-6 HGNC and IFNab; which contribute to the cytokine storm and fever MESHD, parameters of inflammation MESHD d-dimer and ferritin, aberrations in lymphocyte number, lymphopenia MESHD, and neutralizing antibodies were included for the analysis. The model provides a framework to unravel the multi-factorial complexities of the immune response manifested in SARS-CoV-2 infected MESHD individuals. Further, this model can be valuable to predict clinical outcome at an individual level and to develop strategies for allocating appropriate resources to mitigate severe cases at a population level.

    IL-6 HGNC and D-Dimer at Admission Predicts Cardiac Injury MESHD and Early Mortality during SARS-CoV-2 Infection MESHD

    Authors: Daoyuan Si; Beibei Du; Bo Yang; Lina Jin; Lujia Ni; Qian Zhang; Zhongfan Zhang; Mohammed Ali Azam; Patrick F.H Lai; Stephane Masse; Huan Sun; Xingtong Wang; Slava Epelman; Patrick R Lawler; Ping Yang; Kumaraswamy Nanthakumar

    doi:10.1101/2021.03.22.21254077 Date: 2021-03-29 Source: medRxiv

    BACKGROUND: We recently described mortality of cardiac injury MESHD in COVID-19 MESHD patients. Admission activation of immune, thrombotic MESHD biomarkers and their ability to predict cardiac injury MESHD and mortality patterns in COVID-19 MESHD is unknown. METHODS: This retrospective cohort study included 170 COVID-19 MESHD patients with cardiac injury MESHD at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTS: Of 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death MESHD were elevate levels of interleukin 6 HGNC ( IL-6 HGNC) (p<0.0001), Tumor Necrosis Factor-a HGNC Tumor Necrosis Factor-a MESHD ( TNF-a HGNC) (p=0.0025), and C-reactive protein HGNC ( CRP HGNC) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic MESHD pathway activation. Increasing cTnI HGNC levels were associated with those of increasing IL-6 HGNC (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONS: In COVID-19 MESHD patients with cardiac injury MESHD, admission IL-6 HGNC and D-dimer predicted subsequent elevation of cTnI HGNC and early death MESHD, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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