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Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses.
Nat Commun. 2020 11 17; 11(1):5854.NC

Abstract

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.

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Authors+Show Affiliations

Mick E
Division of Infectious Diseases, University of California, San Francisco, CA, USA. Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA. Chan Zuckerberg Biohub, San Francisco, CA, USA.
Kamm J
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Pisco AO
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Ratnasiri K
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Babik JM
Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Castañeda G
Chan Zuckerberg Biohub, San Francisco, CA, USA.
DeRisi JL
Chan Zuckerberg Biohub, San Francisco, CA, USA. Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
Detweiler AM
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Hao SL
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Kangelaris KN
Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Kumar GR
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Li LM
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Mann SA
Chan Zuckerberg Biohub, San Francisco, CA, USA. Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
Neff N
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Prasad PA
Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Serpa PH
Division of Infectious Diseases, University of California, San Francisco, CA, USA. Chan Zuckerberg Biohub, San Francisco, CA, USA.
Shah SJ
Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Spottiswoode N
Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Tan M
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Calfee CS
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
Christenson SA
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
Kistler A
Chan Zuckerberg Biohub, San Francisco, CA, USA.
Langelier C
Division of Infectious Diseases, University of California, San Francisco, CA, USA. chaz.langelier@ucsf.edu. Chan Zuckerberg Biohub, San Francisco, CA, USA. chaz.langelier@ucsf.edu.

MeSH

BetacoronavirusCOVID-19COVID-19 TestingClinical Laboratory TechniquesCoronavirus InfectionsDiagnosis, DifferentialGene ExpressionHost-Pathogen InteractionsHumansImmunity, InnateNasopharynxPandemicsPneumonia, ViralRespiratory Tract InfectionsSARS-CoV-2Sensitivity and SpecificityViral Load

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33203890

Citation

Mick, Eran, et al. "Upper Airway Gene Expression Reveals Suppressed Immune Responses to SARS-CoV-2 Compared With Other Respiratory Viruses." Nature Communications, vol. 11, no. 1, 2020, p. 5854.
Mick E, Kamm J, Pisco AO, et al. Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses. Nat Commun. 2020;11(1):5854.
Mick, E., Kamm, J., Pisco, A. O., Ratnasiri, K., Babik, J. M., Castañeda, G., DeRisi, J. L., Detweiler, A. M., Hao, S. L., Kangelaris, K. N., Kumar, G. R., Li, L. M., Mann, S. A., Neff, N., Prasad, P. A., Serpa, P. H., Shah, S. J., Spottiswoode, N., Tan, M., ... Langelier, C. (2020). Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses. Nature Communications, 11(1), 5854. https://doi.org/10.1038/s41467-020-19587-y
Mick E, et al. Upper Airway Gene Expression Reveals Suppressed Immune Responses to SARS-CoV-2 Compared With Other Respiratory Viruses. Nat Commun. 2020 11 17;11(1):5854. PubMed PMID: 33203890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses. AU - Mick,Eran, AU - Kamm,Jack, AU - Pisco,Angela Oliveira, AU - Ratnasiri,Kalani, AU - Babik,Jennifer M, AU - Castañeda,Gloria, AU - DeRisi,Joseph L, AU - Detweiler,Angela M, AU - Hao,Samantha L, AU - Kangelaris,Kirsten N, AU - Kumar,G Renuka, AU - Li,Lucy M, AU - Mann,Sabrina A, AU - Neff,Norma, AU - Prasad,Priya A, AU - Serpa,Paula Hayakawa, AU - Shah,Sachin J, AU - Spottiswoode,Natasha, AU - Tan,Michelle, AU - Calfee,Carolyn S, AU - Christenson,Stephanie A, AU - Kistler,Amy, AU - Langelier,Charles, Y1 - 2020/11/17/ PY - 2020/05/22/received PY - 2020/10/16/accepted PY - 2020/11/18/entrez PY - 2020/11/19/pubmed PY - 2020/12/1/medline SP - 5854 EP - 5854 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/33203890/Upper_airway_gene_expression_reveals_suppressed_immune_responses_to_SARS_CoV_2_compared_with_other_respiratory_viruses_ DB - PRIME DP - Unbound Medicine ER -