Abstract
The mortality risk of coronavirus disease 2019 (COVID-19) patients has been linked to the cytokine storm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the inflammatory responses shared between COVID-19 and other infectious diseases that feature cytokine storms may therefore help in developing improved therapeutic strategies. Here, we use integrative analysis of single-cell transcriptomes to characterize the inflammatory signatures of peripheral blood mononuclear cells from patients with COVID-19, sepsis, and HIV infection. We identify ten hyperinflammatory cell subtypes in which monocytes are the main contributors to the transcriptional differences in these infections. Monocytes from COVID-19 patients share hyperinflammatory signatures with HIV infection and immunosuppressive signatures with sepsis. Finally, we construct a “three-stage” model of heterogeneity among COVID-19 patients, related to the hyperinflammatory and immunosuppressive signatures in monocytes. Our study thus reveals cellular and molecular insights about inflammatory responses to SARS-CoV-2 infection and provides therapeutic guidance to improve treatments for subsets of COVID-19 patients.
Keywords: COVID-19; SARS-CoV-2; immunosuppression; inflammation.
【저자키워드】 COVID-19, SARS-CoV-2, Inflammation, Immunosuppression, 【초록키워드】 Treatment, coronavirus disease, Monocytes, Inflammation, Coronavirus disease 2019, Cytokine storm, coronavirus, Infectious diseases, Inflammatory responses, SARS-COV-2 infection, Infection, Immunosuppression, Sepsis, Infectious disease, severe acute respiratory syndrome Coronavirus, heterogeneity, monocyte, Peripheral blood, infections, therapeutic, Patient, Peripheral blood mononuclear cells, Therapeutic strategies, understanding, Integrative analysis, Guidance, COVID-19 patients, HIV infection, mortality risk, Inflammatory response, Inflammatory, immunosuppressive, COVID-19 patient, Cytokine storms, other infectious diseases, mononuclear cell, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, help, subtype, single-cell transcriptomes, Hyperinflammatory, Cell, IMPROVE, identify, caused, provide, reveal, subset, cellular and molecular, with HIV, patients with COVID-19, single-cell transcriptome, the cytokine storm, transcriptional difference, 【제목키워드】 monocyte, single-cell analysis, immunosuppressive, Hyperinflammatory, reveal,