Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

There are no transmission terms in the subcorpus


Seroprevalence
    displaying 1 - 2 records in total 2
    records per page




    Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

    Authors: Krystyna Taylor; Sayoni Das; Matthew Pearson; James Kozubek; Marcin Pawlowski; Claus Erik Jensen; Zbigniew Skowron; Gert Lykke Møller; Mark Strivens; Steve Gardner

    doi:10.1101/2020.06.17.20134015 Date: 2020-06-19 Source: medRxiv

    BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia MESHD, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease MESHD, hypertension MESHD hypertension HP and type 2 diabetes mellitus MESHD diabetes mellitus HP. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis MESHD sepsis HP, selecting controls who had not developed sepsis MESHD sepsis HP despite having maximum co-morbidity risk and exposure to sepsis MESHD sepsis HP-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration HP and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease MESHD burden and survival rates.

    SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration HP-like effects

    Authors: Jay Gopalakrishnan; Anand Ramani; Lisa Mueller; Philipp Niklas Ostermann; Elke Gabriel; Abida Islam Pranty; Andreas Mueller-Shiffmann; Aruljothi Mariappan; Oliver Goureau; Henning Gruell; Andreas Walker; Marcel Andree; Sandra Hauka; Kai Wohlgemuth; Heymut Omran; Florian Klein; Dagmar Wieczorek; Ortwin Adams; Joerg Timm; Carsten Korth; Heiner Schaal; Torsten Houwaart; Alexander Dilthey

    doi:10.1101/2020.05.20.106575 Date: 2020-05-20 Source: bioRxiv

    COVID-19 pandemic caused by SARS-CoV-2 infection MESHD is a public health emergency MESHD. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Dusseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum SERO, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death MESHD. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration HP-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19. One sentence summaryCOVID-19 modeling in human brain organoids

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).

Sources


Annotations

All
None
MeSH Disease
Human Phenotype
Transmission
Seroprevalence


Export subcorpus as Endnote

This service is developed in the project nfdi4health task force covid-19 which is a part of nfdi4health.

nfdi4health is one of the funded consortia of the National Research Data Infrastructure programme of the DFG.