Abstract
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.
Highlights
SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19)
We demonstrate that specific immune pathways, namely Type I IFN and Notch signaling, are significantly upregulated in juvenile macaques when compared with old macaques infected with SARS-CoV-2
We report that neutrophil degranulation, innate immune system, and IFN gamma (IFN-γ) signaling pathways are upregulated in both tuberculosis (TB) and COVID-19, two pulmonary infectious diseases where neutrophils accumulation is associated with increased severity
Summary
SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). 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. We show that genes associated with IFN signaling, neutrophil degranulation, and innate immune pathways are significantly induced in the lungs in response to SARS-CoV-2 infection. We demonstrate that specific immune pathways, namely Type I IFN and Notch signaling, are significantly upregulated in juvenile macaques when compared with old macaques infected with SARS-CoV-2. Our study has delineated disease pathways that can serve as a valuable tool in understanding the immunopathogenesis of SARS-CoV-2 infection and progressive COVID-19
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