tetano
Editor, Senior Moderator
Nat Immunol
. 2024 Aug 13.
doi: 10.1038/s41590-024-01914-w. Online ahead of print. Distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia
Nikolay S Markov[SUP] 1 2 [/SUP], Ziyou Ren[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Karolina J Senkow[SUP] #[/SUP][SUP] 1 2 [/SUP], Rogan A Grant[SUP] 1 2 [/SUP], Catherine A Gao[SUP] 1 2 [/SUP], Elizabeth S Malsin[SUP] 1 2 [/SUP], Lango Sichizya[SUP] 1 2 [/SUP], Hermon Kihshen[SUP] 1 2 [/SUP], Kathryn A Helmin[SUP] 1 2 [/SUP], Milica Jovisic[SUP] 1 2 [/SUP], Jason M Arnold[SUP] 1 2 [/SUP], Xóchitl G Pérez-Leonor[SUP] 1 2 [/SUP], Hiam Abdala-Valencia[SUP] 1 2 [/SUP], Suchitra Swaminathan[SUP] 1 2 [/SUP], Julu Nwaezeapu[SUP] 1 2 [/SUP], Mengjia Kang[SUP] 1 2 [/SUP], Luke Rasmussen[SUP] 4 [/SUP], Egon A Ozer[SUP] 5 6 [/SUP], Ramon Lorenzo-Redondo[SUP] 5 6 [/SUP], Judd F Hultquist[SUP] 5 6 [/SUP], Lacy M Simons[SUP] 5 6 [/SUP], Estefany Rios-Guzman[SUP] 5 6 [/SUP], Alexander V Misharin[SUP] 1 2 [/SUP], Richard G Wunderink[SUP] 1 2 [/SUP], G R Scott Budinger[SUP] 1 2 [/SUP], Benjamin D Singer[SUP] #[/SUP][SUP] 1 2 7 8 [/SUP], Luisa Morales-Nebreda[SUP] #[/SUP][SUP] 9 10 [/SUP]; NU SCRIPT Study Investigators
Collaborators, Affiliations
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.
. 2024 Aug 13.
doi: 10.1038/s41590-024-01914-w. Online ahead of print. Distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia
Nikolay S Markov[SUP] 1 2 [/SUP], Ziyou Ren[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Karolina J Senkow[SUP] #[/SUP][SUP] 1 2 [/SUP], Rogan A Grant[SUP] 1 2 [/SUP], Catherine A Gao[SUP] 1 2 [/SUP], Elizabeth S Malsin[SUP] 1 2 [/SUP], Lango Sichizya[SUP] 1 2 [/SUP], Hermon Kihshen[SUP] 1 2 [/SUP], Kathryn A Helmin[SUP] 1 2 [/SUP], Milica Jovisic[SUP] 1 2 [/SUP], Jason M Arnold[SUP] 1 2 [/SUP], Xóchitl G Pérez-Leonor[SUP] 1 2 [/SUP], Hiam Abdala-Valencia[SUP] 1 2 [/SUP], Suchitra Swaminathan[SUP] 1 2 [/SUP], Julu Nwaezeapu[SUP] 1 2 [/SUP], Mengjia Kang[SUP] 1 2 [/SUP], Luke Rasmussen[SUP] 4 [/SUP], Egon A Ozer[SUP] 5 6 [/SUP], Ramon Lorenzo-Redondo[SUP] 5 6 [/SUP], Judd F Hultquist[SUP] 5 6 [/SUP], Lacy M Simons[SUP] 5 6 [/SUP], Estefany Rios-Guzman[SUP] 5 6 [/SUP], Alexander V Misharin[SUP] 1 2 [/SUP], Richard G Wunderink[SUP] 1 2 [/SUP], G R Scott Budinger[SUP] 1 2 [/SUP], Benjamin D Singer[SUP] #[/SUP][SUP] 1 2 7 8 [/SUP], Luisa Morales-Nebreda[SUP] #[/SUP][SUP] 9 10 [/SUP]; NU SCRIPT Study Investigators
Collaborators, Affiliations
- PMID: 39138384
- DOI: 10.1038/s41590-024-01914-w
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.