TY - JOUR
T1 - IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection
AU - Rosa, Bruce A.
AU - Ahmed, Mushtaq
AU - Singh, Dhiraj K.
AU - Choreño-Parra, José Alberto
AU - Cole, Journey
AU - Jiménez-Álvarez, Luis Armando
AU - Rodríguez-Reyna, Tatiana Sofía
AU - Singh, Bindu
AU - Gonzalez, Olga
AU - Carrion, Ricardo
AU - Schlesinger, Larry S.
AU - Martin, John
AU - Zúñiga, Joaquín
AU - Mitreva, Makedonka
AU - Kaushal, Deepak
AU - Khader, Shabaana A.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.
AB - SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.
UR - http://www.scopus.com/inward/record.url?scp=85102209848&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-01829-4
DO - 10.1038/s42003-021-01829-4
M3 - Article
C2 - 33674719
AN - SCOPUS:85102209848
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 290
ER -