ArticleNature immunology2024
Distinctive evolution of alveolar T cell responses is associated with clinical outcomes in unvaccinated patients with SARS-CoV-2 pneumonia.
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Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
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Who cites it
18 citing papers in PubMed.
- The CRAC channel inhibitor Auxora reprograms pathogenic alveolar macrophage-T cell circuits in viral pneumonia.The Journal of clinical investigation · 2026Article
- The challenge and promise of studying human antigen-specific T cells.Nature reviews. Immunology · 2026Review
- Distinct CD8iScience · 2026Article
- Longitudinal clinical proteomics reveals pneumonia type-specific protein biomarkers and autoantibodies.JCI insight · 2026Article
- Comprehensive longitudinal profiling identifies differential frequency, epitope specificity, and effector function of CD8EBioMedicine · 2026Article
- Pathogen-specific host responses define distinct pneumonia endotypes in the human lung.bioRxiv : the preprint server for biology · 2026Article
- Dual-mode aptamer-driven biosensing platform for ultrasensitive and mutation-resilient detection of the SARS-CoV-2 nucleocapsid protein.Genes & diseases · 2026Article
- Alveolar Immune Profiling Identifies Distinct Subphenotypes of Acute Respiratory Failure.medRxiv : the preprint server for health sciences · 2026Article
- Longitudinal clinical proteomics reveals pneumonia type-specific protein biomarkers and autoantibodies.medRxiv : the preprint server for health sciences · 2026Article
- Clinical Characteristics of Mycoplasma pneumoniae Pneumonia in Children and Risk Factors for Progression to Severe Disease.Canadian respiratory journal · 2026Article
- Multi-omics profiling in severe pneumonia: the importance of robust study design.The European respiratory journal · 2025Article
- Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs.Nucleic acids research · 2025Article
- Regulatory T Cells Require TBET to Regulate Activated CD8+ T Cells During Recovery from Influenza.American journal of respiratory cell and molecular biology · 2025Article
- Aging and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19.JCI insight · 2025Article
- Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues.Immunity · 2024Article
- Review
- Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates.Vaccines · 2024Article
- IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN.JCI insight · 2024Article
Corrections and comments
- Update of
Authors and funding
28 authors.
Nikolay S MarkovDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-3659-4387
Ziyou Ren *Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-7127-4197
Karolina J Senkow *Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-9942-3529
Rogan A GrantDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-0655-0882
Catherine A GaoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-5576-3943
Elizabeth S MalsinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-3294-6752
Lango SichizyaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1704-9471
Hermon KihshenDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-8750-0010
Kathryn A HelminDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0009-0006-8857-9943
Milica JovisicDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0009-0004-2278-0535
Jason M ArnoldDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-8687-0063
Xóchitl G Pérez-LeonorDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0009-0006-6617-7927
Hiam Abdala-ValenciaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-3384-5299
Suchitra SwaminathanDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-8292-122X
Julu NwaezeapuDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-7715-5607
Mengjia KangDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1679-9473
Luke RasmussenDivision of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-4497-8049
Egon A OzerDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-7131-3691
Ramon Lorenzo-RedondoDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-5462-9483
Judd F HultquistDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-6424-4280
Lacy M SimonsDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-4041-6775
Estefany Rios-GuzmanDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1399-7546
Alexander V MisharinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-2879-3789
Richard G WunderinkDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-8527-4195
G R Scott BudingerDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-3114-5208
Benjamin D Singer *Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-5775-8427
Luisa Morales-Nebreda *Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. luisamorales@northwestern.edu.ORCID http://orcid.org/0000-0002-7126-0518
NU SCRIPT Study Investigators
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9MNorthwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MTissue resident macrophages regulate proteostasis in the aging lungP01AG049665 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GR Scott Budinger · 2015 to 2026
$26.9MTechnology CoreU19AI135964 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LUIS A. Nunes AMARAL · 2018 to 2026
$24.7MThe Cell Phenotyping and Mouse CoreP01HL154998 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KAREN M RIDGE · 2021 to 2026
$18.9MPREDOCTORAL AND POSTDOCTORAL TRAINING PROGRAM IN AGING AND DEMENTIAT32AG020506 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ROBERT J VASSAR, SANDRA WEINTRAUB · 2002 to 2026
$9.9MTraining Program In Lung SciencesT32HL076139 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KAREN M RIDGE, Jacob I Sznajder · 2004 to 2026
$9.6MThe Neu-Lung Consortium: Neutrophilic Mechanisms of Inflammation, Injury, and Repair in Lung and Airways DiseasesU19AI181102 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Stephanie Caroline Eisenbarth, Alexander Misharin · 2024 to 2026
$9.3MTRAINING PROGRAM IN IMMUNOLOGY &MOLECULAR PATHOGENESIST32AI007476 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Edward Benjamin Thorp · 1996 to 2026
$6.6MRole of spleen educated monocytes in mediating ischemia-reperfusion injury followinglung transplant surgeryR01HL147575 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ankit Bharat, GR Scott Budinger · 2019 to 2026
$5.5MPathogenesis of lung injury mediated by lung-restricted antibodiesR01HL147290 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Ankit Bharat, GR Scott Budinger · 2019 to 2026
$5.2MCRITICAL: Collaborative Resource for Intensive care Translational science, Informatics, Comprehensive Analytics, and LearningU01TR003528 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CIMINO, JAMES J, LUO, YUAN · 2021 to 2024
$4.9MAmerican Heart Association-American Stroke Association 24PRE1196998CSRD VA I01 CX001777NCATS NIH HHS U01 TR003528NCATS NIH HHS UL1 TR001422NCI NIH HHS P30 CA060553NHLBI NIH HHS F32 HL162377NHLBI NIH HHS K23 HL169815NHLBI NIH HHS P01 HL154998NHLBI NIH HHS R01 HL094643NHLBI NIH HHS R01 HL134800NHLBI NIH HHS R01 HL147290NHLBI NIH HHS R01 HL147575NHLBI NIH HHS R01 HL149883NHLBI NIH HHS R01 HL153122NHLBI NIH HHS R01 HL153312NHLBI NIH HHS R01 HL158139NHLBI NIH HHS T32 HL076139NIAID NIH HHS R01 AI177498NIAID NIH HHS T32 AI007476NIAID NIH HHS U19 AI135964NIAID NIH HHS U19 AI181102NIA NIH HHS F31 AG071225NIA NIH HHS P01 AG049665NIA NIH HHS R21 AG075423NIA NIH HHS T32 AG020506NIEHS NIH HHS R01 ES034350NLM NIH HHS R01 LM013337U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U19AI135964
Abstract
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.
Indexed as
COVID-19NF-kappa BSARS-CoV-2AdultAgedBronchoalveolar Lavage FluidFemaleHumansInterferonsMaleMiddle AgedPulmonary AlveoliSignal TransductionSpike Glycoprotein, CoronavirusT-LymphocytesT-Lymphocyte SubsetsInterferonsNF-kappa BSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2
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