Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses

Eran Mick, Jack Kamm, Angela Oliveira Pisco, Kalani Ratnasiri, Jennifer M. Babik, Gloria Castañeda, Joseph L. DeRisi, Angela M. Detweiler, Samantha L. Hao, Kirsten N. Kangelaris, G. Renuka Kumar, Lucy M. Li, Sabrina A. Mann, Norma Neff, Priya A. Prasad, Paula Hayakawa Serpa, Sachin J. Shah, Natasha Spottiswoode, Michelle Tan, Carolyn S. Calfee, Stephanie A. Christenson, Amy Kistler and Charles Langelier ()
Additional contact information
Eran Mick: University of California
Jack Kamm: Chan Zuckerberg Biohub
Angela Oliveira Pisco: Chan Zuckerberg Biohub
Kalani Ratnasiri: Chan Zuckerberg Biohub
Jennifer M. Babik: University of California
Gloria Castañeda: Chan Zuckerberg Biohub
Joseph L. DeRisi: Chan Zuckerberg Biohub
Angela M. Detweiler: Chan Zuckerberg Biohub
Samantha L. Hao: Chan Zuckerberg Biohub
Kirsten N. Kangelaris: University of California
G. Renuka Kumar: Chan Zuckerberg Biohub
Lucy M. Li: Chan Zuckerberg Biohub
Sabrina A. Mann: Chan Zuckerberg Biohub
Norma Neff: Chan Zuckerberg Biohub
Priya A. Prasad: University of California
Paula Hayakawa Serpa: University of California
Sachin J. Shah: University of California
Natasha Spottiswoode: University of California
Michelle Tan: Chan Zuckerberg Biohub
Carolyn S. Calfee: University of California
Stephanie A. Christenson: University of California
Amy Kistler: Chan Zuckerberg Biohub
Charles Langelier: University of California

Nature Communications, 2020, vol. 11, issue 1, 1-7

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19587-y

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