Activation of Intracellular Complement in Lungs of Patients With Severe COVID-19 Disease Decreases T-Cell Activity in the Lungs

A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives...

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Bibliographic Details
Published in:Frontiers in immunology 2021-11, Vol.12, p.700705-700705
Main Authors: Howell, Mark C, Green, Ryan, McGill, Andrew R, Kahlil, Roukiah M, Dutta, Rinku, Mohapatra, Shyam S, Mohapatra, Subhra
Format: Article
Language:English
Subjects:
bioinformatics
complement
Complement Activation - genetics
Complement System Proteins - genetics
COVID-19 - genetics
COVID-19 - immunology
COVID-19 - virology
Gene Expression Profiling - methods
Gene Regulatory Networks - genetics
Humans
Immunology
Intracellular Space - genetics
Lung - immunology
Lung - metabolism
Lung - microbiology
lungs
Lymphocyte Count
SARS-CoV-2 - physiology
severe COVID-19 disease
T-cells
T-Lymphocyte Subsets - metabolism
T-Lymphocytes - metabolism
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Summary:A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear. To shed light on the potential mechanisms, we examined publicly available RNA-Sequencing data using CIBERSORTx and conducted a Ingenuity Pathway Analysis to address this knowledge gap. In complement to these findings, we used bioinformatics tools to analyze publicly available RNA sequencing data and found that upregulation of complement may be leading to a downregulation of T-cell activity in lungs of severe COVID-19 patients. Thus, targeting treatments aimed at the modulation of classical complement and T-cell activity may help alleviate the proinflammatory effects of COVID-19, reduce lung pathology, and increase the survival of COVID-19 patients.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.700705