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Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals...

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Autores principales: Avadhanula, Vasanthi, Creighton, Chad J., Ferlic-Stark, Laura, Sucgang, Richard, Zhang, Yiqun, Nagaraj, Divya, Nicholson, Erin G., Rajan, Anubama, Menon, Vipin Kumar, Doddapaneni, Harshavardhan, Muzny, Donna Marie, Metcalf, Ginger, Cregeen, Sara Joan Javornik, Hoffman, Kristi Louise, Gibbs, Richard A, Petrosino, Joseph, Piedra, Pedro A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245966/
https://www.ncbi.nlm.nih.gov/pubmed/37292999
http://dx.doi.org/10.1101/2023.05.24.542181
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author Avadhanula, Vasanthi
Creighton, Chad J.
Ferlic-Stark, Laura
Sucgang, Richard
Zhang, Yiqun
Nagaraj, Divya
Nicholson, Erin G.
Rajan, Anubama
Menon, Vipin Kumar
Doddapaneni, Harshavardhan
Muzny, Donna Marie
Metcalf, Ginger
Cregeen, Sara Joan Javornik
Hoffman, Kristi Louise
Gibbs, Richard A
Petrosino, Joseph
Piedra, Pedro A
author_facet Avadhanula, Vasanthi
Creighton, Chad J.
Ferlic-Stark, Laura
Sucgang, Richard
Zhang, Yiqun
Nagaraj, Divya
Nicholson, Erin G.
Rajan, Anubama
Menon, Vipin Kumar
Doddapaneni, Harshavardhan
Muzny, Donna Marie
Metcalf, Ginger
Cregeen, Sara Joan Javornik
Hoffman, Kristi Louise
Gibbs, Richard A
Petrosino, Joseph
Piedra, Pedro A
author_sort Avadhanula, Vasanthi
collection PubMed
description Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes correlated with SARS-CoV-2 viral load over time were similarly differentially expressed across independent datasets of SARS-CoV-2 infected lung and upper airway cells, from both in vitro systems and patient samples. We also generated expression data on the human nose organoid model during SARS-CoV-2 infection. The human nose organoid-generated host transcriptional response captured many aspects of responses observed in the above patient samples, while suggesting the existence of distinct host responses to SARS-CoV-2 depending on the cellular context, involving both epithelial and cellular immune responses. Our findings provide a catalog of SARS-CoV-2 host response genes changing over time.
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spelling pubmed-102459662023-06-08 Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load Avadhanula, Vasanthi Creighton, Chad J. Ferlic-Stark, Laura Sucgang, Richard Zhang, Yiqun Nagaraj, Divya Nicholson, Erin G. Rajan, Anubama Menon, Vipin Kumar Doddapaneni, Harshavardhan Muzny, Donna Marie Metcalf, Ginger Cregeen, Sara Joan Javornik Hoffman, Kristi Louise Gibbs, Richard A Petrosino, Joseph Piedra, Pedro A bioRxiv Article Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes correlated with SARS-CoV-2 viral load over time were similarly differentially expressed across independent datasets of SARS-CoV-2 infected lung and upper airway cells, from both in vitro systems and patient samples. We also generated expression data on the human nose organoid model during SARS-CoV-2 infection. The human nose organoid-generated host transcriptional response captured many aspects of responses observed in the above patient samples, while suggesting the existence of distinct host responses to SARS-CoV-2 depending on the cellular context, involving both epithelial and cellular immune responses. Our findings provide a catalog of SARS-CoV-2 host response genes changing over time. Cold Spring Harbor Laboratory 2023-05-25 /pmc/articles/PMC10245966/ /pubmed/37292999 http://dx.doi.org/10.1101/2023.05.24.542181 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Avadhanula, Vasanthi
Creighton, Chad J.
Ferlic-Stark, Laura
Sucgang, Richard
Zhang, Yiqun
Nagaraj, Divya
Nicholson, Erin G.
Rajan, Anubama
Menon, Vipin Kumar
Doddapaneni, Harshavardhan
Muzny, Donna Marie
Metcalf, Ginger
Cregeen, Sara Joan Javornik
Hoffman, Kristi Louise
Gibbs, Richard A
Petrosino, Joseph
Piedra, Pedro A
Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
title Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
title_full Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
title_fullStr Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
title_full_unstemmed Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
title_short Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load
title_sort longitudinal host transcriptional responses to sars-cov-2 infection in adults with extremely high viral load
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245966/
https://www.ncbi.nlm.nih.gov/pubmed/37292999
http://dx.doi.org/10.1101/2023.05.24.542181
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