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COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions

COVID-19 can be life-threatening to individuals with chronic diseases. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities found in common health conditions that predispose patients to poor prognoses. In this study, we focused on 14 pre-existing health...

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Autores principales: Lee, Matthew, Chang, Yung, Ahmadinejad, Navid, Johnson-Agbakwu, Crista, Bailey, Celeste, Liu, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083528/
https://www.ncbi.nlm.nih.gov/pubmed/35547187
http://dx.doi.org/10.7717/peerj.13227
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author Lee, Matthew
Chang, Yung
Ahmadinejad, Navid
Johnson-Agbakwu, Crista
Bailey, Celeste
Liu, Li
author_facet Lee, Matthew
Chang, Yung
Ahmadinejad, Navid
Johnson-Agbakwu, Crista
Bailey, Celeste
Liu, Li
author_sort Lee, Matthew
collection PubMed
description COVID-19 can be life-threatening to individuals with chronic diseases. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities found in common health conditions that predispose patients to poor prognoses. In this study, we focused on 14 pre-existing health conditions for which increased hazard ratios of COVID-19 mortality have been documented. We hypothesized that dysregulated gene expression in these pre-existing health conditions were risk factors of COVID-19 related death, and the magnitude of dysregulation (measured by fold change) were correlated with the severity of COVID-19 outcome (measured by hazard ratio). To test this hypothesis, we analyzed transcriptomics data sets archived before the pandemic in which no sample had COVID-19. For a given pre-existing health condition, we identified differentially expressed genes by comparing individuals affected by this health condition with those unaffected. Among genes differentially expressed in multiple health conditions, the fold changes of 70 upregulated genes and 181 downregulated genes were correlated with hazard ratios of COVID-19 mortality. These pre-existing dysregulations were molecular risk factors of severe COVID-19 outcomes. These genes were enriched with endoplasmic reticulum and mitochondria function, proinflammatory reaction, interferon production, and programmed cell death that participate in viral replication and innate immune responses to viral infections. Our results suggest that impaired innate immunity in pre-existing health conditions is associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic intervention.
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spelling pubmed-90835282022-05-10 COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions Lee, Matthew Chang, Yung Ahmadinejad, Navid Johnson-Agbakwu, Crista Bailey, Celeste Liu, Li PeerJ Bioinformatics COVID-19 can be life-threatening to individuals with chronic diseases. To prevent severe outcomes, it is critical that we comprehend pre-existing molecular abnormalities found in common health conditions that predispose patients to poor prognoses. In this study, we focused on 14 pre-existing health conditions for which increased hazard ratios of COVID-19 mortality have been documented. We hypothesized that dysregulated gene expression in these pre-existing health conditions were risk factors of COVID-19 related death, and the magnitude of dysregulation (measured by fold change) were correlated with the severity of COVID-19 outcome (measured by hazard ratio). To test this hypothesis, we analyzed transcriptomics data sets archived before the pandemic in which no sample had COVID-19. For a given pre-existing health condition, we identified differentially expressed genes by comparing individuals affected by this health condition with those unaffected. Among genes differentially expressed in multiple health conditions, the fold changes of 70 upregulated genes and 181 downregulated genes were correlated with hazard ratios of COVID-19 mortality. These pre-existing dysregulations were molecular risk factors of severe COVID-19 outcomes. These genes were enriched with endoplasmic reticulum and mitochondria function, proinflammatory reaction, interferon production, and programmed cell death that participate in viral replication and innate immune responses to viral infections. Our results suggest that impaired innate immunity in pre-existing health conditions is associated with increased hazard of COVID-19 mortality. The discovered molecular risk factors are potential prognostic biomarkers and targets for therapeutic intervention. PeerJ Inc. 2022-05-06 /pmc/articles/PMC9083528/ /pubmed/35547187 http://dx.doi.org/10.7717/peerj.13227 Text en © 2022 Lee et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Lee, Matthew
Chang, Yung
Ahmadinejad, Navid
Johnson-Agbakwu, Crista
Bailey, Celeste
Liu, Li
COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions
title COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions
title_full COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions
title_fullStr COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions
title_full_unstemmed COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions
title_short COVID-19 mortality is associated with pre-existing impaired innate immunity in health conditions
title_sort covid-19 mortality is associated with pre-existing impaired innate immunity in health conditions
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083528/
https://www.ncbi.nlm.nih.gov/pubmed/35547187
http://dx.doi.org/10.7717/peerj.13227
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