RESUMEN
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.
Asunto(s)
COVID-19/sangre , COVID-19/inmunología , Infecciones por VIH/sangre , Leucocitos Mononucleares/metabolismo , SARS-CoV-2/inmunología , Sepsis/sangre , Transcriptoma , COVID-19/virología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/inmunología , Citocinas/sangre , Análisis de Datos , Conjuntos de Datos como Asunto , Infecciones por VIH/inmunología , VIH-1/inmunología , Humanos , Terapia de Inmunosupresión , Inflamación/sangre , Leucocitos Mononucleares/inmunología , Sepsis/inmunología , Análisis de la Célula IndividualRESUMEN
Several studies show that the immunosuppressive drugs targeting the interleukin-6 (IL-6) receptor, including tocilizumab, ameliorate lethal inflammatory responses in COVID-19 patients infected with SARS-CoV-2. Here, by employing single-cell analysis of the immune cell composition of two severe-stage COVID-19 patients prior to and following tocilizumab-induced remission, we identify a monocyte subpopulation that contributes to the inflammatory cytokine storms. Furthermore, although tocilizumab treatment attenuates the inflammation, immune cells, including plasma B cells and CD8+ T cells, still exhibit robust humoral and cellular antiviral immune responses. Thus, in addition to providing a high-dimensional dataset on the immune cell distribution at multiple stages of the COVID-19, our work also provides insights into the therapeutic effects of tocilizumab, and identifies potential target cell populations for treating COVID-19-related cytokine storms.