Human endogenous retrovirus K activation in the lower respiratory tract of severe COVID-19 patients associates with early mortality

Autor: Felipe Betoni, Thiago Moreno L. Souza, Remy Martins-Gonçalves, Eugenio D. Hottz, Carolina Q. Sacramento, Monique Cristina dos Santos, Aline C.A. Silva, Isaclaudia G. de Azevedo-Quintanilha, João Gesto, Emilly Caroline Moraes, Juliana L. Abrantes, Marcelo da Costa Ferreira, Carlos M. Morel, Jairo R. Temerozo, Hongdong Tan, Hui Jiang, Patrícia T. Bozza, Monique R.O. Trugilho, Dumith Chequer Bou-Habib, Cassia Righy, Samuel Mandacaru, Natalia Fintelman-Rodrigues, Fernando A. Bozza, Pedro Kurtz
Rok vydání: 2021
Předmět:
Popis: Critically ill 2019 coronavirus disease patients (COVID-19) under invasive mechanical ventilation (IMV) are 10- to 40-times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation and coagulopathy, the mechanisms involved in progression to severity are poorly understood. By analyzing the virome from tracheal aspirates (TA) of 25 COVID-19 patients under IMV, we found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes compared to nasopharyngeal swabs from mild cases and TA from non-COVID patients. Proteomic analysis and RT-PCR confirmed the presence of HERV-K in these patients. Moreover, increased HERV-K expression was triggered in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days) in the intensive care unit. Increased HERV-K expression in deceased patients associated with IL-17-related inflammation, monocyte activation and higher consumption of clotting/fibrinolysis factors. Our data implicate the levels of HERV-K transcripts in the outcome of critical COVID-19 patients under invasive mechanical ventilation.
Databáze: OpenAIRE