TY - JOUR
T1 - Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
AU - McClain, Micah T.
AU - Constantine, Florica J.
AU - Henao, Ricardo
AU - Liu, Yiling
AU - Tsalik, Ephraim L.
AU - Burke, Thomas W.
AU - Steinbrink, Julie M.
AU - Petzold, Elizabeth
AU - Nicholson, Bradly P.
AU - Rolfe, Robert
AU - Kraft, Bryan D.
AU - Kelly, Matthew S.
AU - Saban, Daniel R.
AU - Yu, Chen
AU - Shen, Xiling
AU - Ko, Emily M.
AU - Sempowski, Gregory D.
AU - Denny, Thomas N.
AU - Ginsburg, Geoffrey S.
AU - Woods, Christopher W.
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2021/12/1
Y1 - 2021/12/1
N2 - SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
AB - SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
UR - https://www.nature.com/articles/s41467-021-21289-y
UR - http://www.scopus.com/inward/record.url?scp=85101160496&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-21289-y
DO - 10.1038/s41467-021-21289-y
M3 - Article
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -
