Distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia.
Nikolay S MarkovZiyou RenKarolina J SenkowRogan A GrantCatherine Aiyuan GaoElizabeth S MalsinLango SichizyaHermon KihshenKathryn A HelminMilica JovisicJason M ArnoldXóchitl G Pérez-LeonorHiam Abdala-ValenciaSuchitra SwaminathanJulu NwaezeapuMengjia KangLuke V RasmussenEgon Anderson OzerRamon Lorenzo-RedondoJudd F HultquistLacy M SimonsEstefany R GuzmanAlexander V MisharinRichard G WunderinkG R Scott BudingerBenjamin David SingerLuisa Morales-Nebredanull nullPublished in: Nature immunology (2024)
The evolution of T cell molecular signatures in the distal lung of patients with severe pneumonia is understudied. Here, we analyzed T cell subsets in longitudinal bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia, including unvaccinated patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with respiratory failure not linked to pneumonia. In patients with SARS-CoV-2 pneumonia, activation of interferon signaling pathways, low activation of the NF-κB pathway and preferential targeting of spike and nucleocapsid proteins early after intubation were associated with favorable outcomes, whereas loss of interferon signaling, activation of NF-κB-driven programs and specificity for the ORF1ab complex late in disease were associated with mortality. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize individuals who recover, whereas responses against nonstructural proteins and activation of NF-κB are associated with poor outcomes.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- respiratory failure
- signaling pathway
- extracorporeal membrane oxygenation
- dendritic cells
- community acquired pneumonia
- pi k akt
- oxidative stress
- end stage renal disease
- coronavirus disease
- mechanical ventilation
- early onset
- public health
- newly diagnosed
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- acute respiratory distress syndrome
- induced apoptosis
- drug induced
- dna methylation
- risk factors
- cardiovascular events
- intensive care unit
- cross sectional
- inflammatory response
- metabolic syndrome
- genome wide
- drug delivery
- endoplasmic reticulum stress