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, Charles Langelier
Author Information
Eran Mick: Division of Infectious Diseases, University of California, San Francisco, CA, USA. ORCID
Jack Kamm: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Angela Oliveira Pisco: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Kalani Ratnasiri: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Jennifer M Babik: Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Gloria Castañeda: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Joseph L DeRisi: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Angela M Detweiler: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Samantha L Hao: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Kirsten N Kangelaris: Division of Hospital Medicine, University of California, San Francisco, CA, USA.
G Renuka Kumar: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Lucy M Li: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Sabrina A Mann: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Norma Neff: Chan Zuckerberg Biohub, San Francisco, CA, USA. ORCID
Priya A Prasad: Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Paula Hayakawa Serpa: Division of Infectious Diseases, University of California, San Francisco, CA, USA.
Sachin J Shah: Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Natasha Spottiswoode: Division of Hospital Medicine, University of California, San Francisco, CA, USA.
Michelle Tan: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Carolyn S Calfee: Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
Stephanie A Christenson: Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA, USA.
Amy Kistler: Chan Zuckerberg Biohub, San Francisco, CA, USA.
Charles Langelier: Division of Infectious Diseases, University of California, San Francisco, CA, USA. chaz.langelier@ucsf.edu. ORCID
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.
