Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

• Published in: Nature communications Vol. 12; no. 1; p. 1079
• Main Authors: McClain, Micah T., Constantine, Florica J., Henao, Ricardo, Liu, Yiling, Tsalik, Ephraim L., Burke, Thomas W., Steinbrink, Julie M., Petzold, Elizabeth, Nicholson, Bradly P., Rolfe, Robert, Kraft, Bryan D., Kelly, Matthew S., Saban, Daniel R., Yu, Chen, Shen, Xiling, Ko, Emily M., Sempowski, Gregory D., Denny, Thomas N., Ginsburg, Geoffrey S., Woods, Christopher W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 38/91; 631/250/255/2514; 631/326/2521; 631/326/596/4130; Antibodies; Biomarkers; Blood; Cell activation; Coagulation; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - genetics; COVID-19 - virology; Cytokines - genetics; Fibrin; Gene expression; Gene Expression Profiling - methods; Gene sequencing; Host-Pathogen Interactions; Humanities and Social Sciences; Humans; Immune response; Immune system; Infections; Influenza; Influenza, Human - genetics; Interferon; Interleukin 1; Leukocytes, Mononuclear - metabolism; Lymphocytes B; multidisciplinary; Peripheral blood; Pneumonia, Bacterial - genetics; Ribonucleic acid; RNA; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Sequence Analysis, RNA - methods; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signal Transduction - genetics; Transcription; Transcriptome - genetics; Transcriptomes; Transcriptomics; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21289-y

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. The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.