{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:33:03Z","timestamp":1779179583795,"version":"3.51.4"},"posted":{"date-parts":[[2023,12,14]]},"group-title":"Systems Biology","reference-count":99,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:sup>+<\/jats:sup>\n                  and CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cell subsets. In patients with COVID-19 but not pneumonia secondary to other pathogens, we found that early and persistent enrichment in CD8\n                  <jats:sup>+<\/jats:sup>\n                  and CD4\n                  <jats:sup>+<\/jats:sup>\n                  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-\u03baB-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-\u03baB activation against non-structural proteins in patients who go on to experience poor clinical outcomes.\n                <\/jats:p>","DOI":"10.1101\/2023.12.13.571479","type":"posted-content","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T21:50:18Z","timestamp":1702590618000},"source":"Crossref","is-referenced-by-count":3,"title":["A distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-4387","authenticated-orcid":false,"given":"Nikolay 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