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Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2

We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune r...

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Autores principales: Mick, Eran, Kamm, Jack, Pisco, Angela Oliveira, Ratnasiri, Kalani, Babik, Jennifer M., Calfee, Carolyn S., Castañeda, Gloria, DeRisi, Joseph L., Detweiler, Angela M., Hao, Samantha, Kangelaris, Kirsten N., Kumar, G. Renuka, Li, Lucy M., Mann, Sabrina A., Neff, Norma, Prasad, Priya A., Serpa, Paula Hayakawa, Shah, Sachin J., Spottiswoode, Natasha, Tan, Michelle, Christenson, Stephanie A., Kistler, Amy, Langelier, Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273244/
https://www.ncbi.nlm.nih.gov/pubmed/32511476
http://dx.doi.org/10.1101/2020.05.18.20105171
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author Mick, Eran
Kamm, Jack
Pisco, Angela Oliveira
Ratnasiri, Kalani
Babik, Jennifer M.
Calfee, Carolyn S.
Castañeda, Gloria
DeRisi, Joseph L.
Detweiler, Angela M.
Hao, Samantha
Kangelaris, Kirsten N.
Kumar, G. Renuka
Li, Lucy M.
Mann, Sabrina A.
Neff, Norma
Prasad, Priya A.
Serpa, Paula Hayakawa
Shah, Sachin J.
Spottiswoode, Natasha
Tan, Michelle
Christenson, Stephanie A.
Kistler, Amy
Langelier, Charles
author_facet Mick, Eran
Kamm, Jack
Pisco, Angela Oliveira
Ratnasiri, Kalani
Babik, Jennifer M.
Calfee, Carolyn S.
Castañeda, Gloria
DeRisi, Joseph L.
Detweiler, Angela M.
Hao, Samantha
Kangelaris, Kirsten N.
Kumar, G. Renuka
Li, Lucy M.
Mann, Sabrina A.
Neff, Norma
Prasad, Priya A.
Serpa, Paula Hayakawa
Shah, Sachin J.
Spottiswoode, Natasha
Tan, Michelle
Christenson, Stephanie A.
Kistler, Amy
Langelier, Charles
author_sort Mick, Eran
collection PubMed
description We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune response, with reduced expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation and interactions with lymphoid cells. Patients with COVID-19 also exhibited significantly reduced proportions of neutrophils and macrophages, and increased proportions of goblet, dendritic and B-cells, compared to other viral ARIs. Using machine learning, we built 26-, 10- and 3-gene classifiers that differentiated COVID-19 from other acute respiratory illnesses with AUCs of 0.980, 0.950 and 0.871, respectively. Classifier performance was stable at low viral loads, suggesting utility in settings where direct detection of viral nucleic acid may be unsuccessful. Taken together, our results illuminate unique aspects of the host transcriptional response to SARS-CoV-2 in comparison to other respiratory viruses and demonstrate the feasibility of COVID-19 diagnostics based on patient gene expression.
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spelling pubmed-72732442020-06-07 Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2 Mick, Eran Kamm, Jack Pisco, Angela Oliveira Ratnasiri, Kalani Babik, Jennifer M. Calfee, Carolyn S. Castañeda, Gloria DeRisi, Joseph L. Detweiler, Angela M. Hao, Samantha Kangelaris, Kirsten N. Kumar, G. Renuka Li, Lucy M. Mann, Sabrina A. Neff, Norma Prasad, Priya A. Serpa, Paula Hayakawa Shah, Sachin J. Spottiswoode, Natasha Tan, Michelle Christenson, Stephanie A. Kistler, Amy Langelier, Charles medRxiv Article We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune response, with reduced expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation and interactions with lymphoid cells. Patients with COVID-19 also exhibited significantly reduced proportions of neutrophils and macrophages, and increased proportions of goblet, dendritic and B-cells, compared to other viral ARIs. Using machine learning, we built 26-, 10- and 3-gene classifiers that differentiated COVID-19 from other acute respiratory illnesses with AUCs of 0.980, 0.950 and 0.871, respectively. Classifier performance was stable at low viral loads, suggesting utility in settings where direct detection of viral nucleic acid may be unsuccessful. Taken together, our results illuminate unique aspects of the host transcriptional response to SARS-CoV-2 in comparison to other respiratory viruses and demonstrate the feasibility of COVID-19 diagnostics based on patient gene expression. Cold Spring Harbor Laboratory 2020-05-22 /pmc/articles/PMC7273244/ /pubmed/32511476 http://dx.doi.org/10.1101/2020.05.18.20105171 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/It is made available under a CC-BY-NC-ND 4.0 International license (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Article
Mick, Eran
Kamm, Jack
Pisco, Angela Oliveira
Ratnasiri, Kalani
Babik, Jennifer M.
Calfee, Carolyn S.
Castañeda, Gloria
DeRisi, Joseph L.
Detweiler, Angela M.
Hao, Samantha
Kangelaris, Kirsten N.
Kumar, G. Renuka
Li, Lucy M.
Mann, Sabrina A.
Neff, Norma
Prasad, Priya A.
Serpa, Paula Hayakawa
Shah, Sachin J.
Spottiswoode, Natasha
Tan, Michelle
Christenson, Stephanie A.
Kistler, Amy
Langelier, Charles
Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
title Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
title_full Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
title_fullStr Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
title_full_unstemmed Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
title_short Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2
title_sort upper airway gene expression differentiates covid-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273244/
https://www.ncbi.nlm.nih.gov/pubmed/32511476
http://dx.doi.org/10.1101/2020.05.18.20105171
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