RESUMEN
The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.
Asunto(s)
Anticuerpos Antivirales/sangre , Proteínas Sanguíneas/metabolismo , COVID-19/diagnóstico , Síndrome de Liberación de Citoquinas/diagnóstico , Endotelio Vascular/virología , Linfopenia/diagnóstico , SARS-CoV-2/patogenicidad , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/virología , Quimiocina CXCL10/sangre , Quimiocina CXCL9/sangre , Análisis por Conglomerados , Convalecencia , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/mortalidad , Síndrome de Liberación de Citoquinas/virología , Progresión de la Enfermedad , Endotelio Vascular/inmunología , Granulocitos/inmunología , Granulocitos/virología , Factores de Crecimiento de Célula Hematopoyética/sangre , Factor de Crecimiento de Hepatocito/sangre , Humanos , Unidades de Cuidados Intensivos , Subunidad p40 de la Interleucina-12/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/virología , Lectinas Tipo C/sangre , Linfopenia/inmunología , Linfopenia/mortalidad , Linfopenia/virología , Células Plasmáticas/inmunología , Células Plasmáticas/virología , Análisis de Supervivencia , Linfocitos T/inmunología , Linfocitos T/virologíaRESUMEN
COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS-CoV-2-driven ARDS.