Por favor, use este identificador para citar o enlazar este ítem:
http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/8438| A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia | |
| Nikolay Markov Ziyou Ren Karolina Senkow Rogan Grant Catherine A. Gao Elizabeth Malsin Lango Sichizya Hermon Kihshen Kathryn Helmin Milica Jovisic Jason Arnold Xóchitl G. Pérez-Leonor Hiam Abdala Valencia Suchitra Swaminathan Julu Nwaezeapu Mengjia Kang Luke Rasmussen Egon Ozer Ramon Lorenzo_Redondo Judd Hultquist Lacy Simons Estefany Guzman Alexander Misharin Richard Wunderink GR Scott Budinger Benjamin Singer Luisa Morales-Nebreda | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2023.12.13.571479 | |
| https://www.biorxiv.org/content/10.1101/2023.12.13.571479v1 | |
| Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied. Accordingly, we serially obtained 432 bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia and respiratory failure, including 74 unvaccinated patients with COVID-19, and performed flow cytometry, transcriptional, and T cell receptor profiling on sorted CD8+ and CD4+ T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8+ and CD4+ T cell subsets correlated with survival to hospital discharge. Activation of interferon signaling pathways early after intubation for COVID-19 was associated with favorable outcomes, while activation of NF-κB-driven programs late in disease was associated with poor outcomes. Patients with SARS-CoV-2 pneumonia whose alveolar T cells preferentially targeted the Spike and Nucleocapsid proteins tended to experience more favorable outcomes than patients whose T cells predominantly targeted the ORF1ab polyprotein complex. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize patients who recover, yet these responses progress to NF-κB activation against non-structural proteins in patients who go on to experience poor clinical outcomes. | |
| bioRxiv | |
| 14-12-2023 | |
| Preimpreso | |
| Inglés | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Materiales de Consulta y Comunicados Técnicos |
Cargar archivos:
| Fichero | Tamaño | Formato | |
|---|---|---|---|
| A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia.pdf | 28.42 MB | Adobe PDF | Visualizar/Abrir |