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Journal article
Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
Science translational medicine, v 16(743)
17 Apr 2024
PMID: 38630846
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Age is a major risk factor for severe coronavirus disease 2019 (COVID-19), yet the mechanisms behind this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host immune response in the blood and the upper airway, as well as the nasal microbiome in a prospective, multicenter cohort of 1031 vaccine-naïve patients hospitalized for COVID-19 between 18 and 96 years old. We performed mass cytometry, serum protein profiling, anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays, and blood and nasal transcriptomics. We found that older age correlated with increased SARS-CoV-2 viral abundance upon hospital admission, delayed viral clearance, and increased type I interferon gene expression in both the blood and upper airway. We also observed age-dependent up-regulation of innate immune signaling pathways and down-regulation of adaptive immune signaling pathways. Older adults had lower naïve T and B cell populations and higher monocyte populations. Over time, older adults demonstrated a sustained induction of pro-inflammatory genes and serum chemokines compared with younger individuals, suggesting an age-dependent impairment in inflammation resolution. Transcriptional and protein biomarkers of disease severity differed with age, with the oldest adults exhibiting greater expression of pro-inflammatory genes and proteins in severe disease. Together, our study finds that aging is associated with impaired viral clearance, dysregulated immune signaling, and persistent and potentially pathologic activation of pro-inflammatory genes and proteins.
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Details
- Title
- Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
- Creators
- Hoang Van Phan - University of California, San FranciscoAlexandra Tsitsiklis - University of California, San FranciscoCole P Maguire - The University of Texas at AustinElias K Haddad - Drexel UniversityPatrice M Becker - National Institute of Allergy and Infectious DiseasesSeunghee Kim-Schulze - Icahn School of Medicine at Mount SinaiBrian Lee - Icahn School of Medicine at Mount SinaiJing Chen - Boston Children's HospitalAnnmarie Hoch - Boston Children's HospitalHarry Pickering - David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USAPatrick van Zalm - Boston Children's HospitalMatthew C Altman - University of WashingtonAlison D Augustine - National Institute of Allergy and Infectious DiseasesCarolyn S Calfee - University of California, San FranciscoSteve Bosinger - Emory and Henry CollegeCharles B Cairns - Drexel University, Tower Health Hospital, Philadelphia, PA 19104, USAWalter Eckalbar - University of California, San FranciscoLeying Guan - Yale School of Public Health, New Haven, CT 06510, USANaresh Doni Jayavelu - University of WashingtonSteven H Kleinstein - Yale School of MedicineFlorian Krammer - Icahn School of Medicine at Mount SinaiHolden T Maecker - Stanford University School of MedicineAl Ozonoff - Boston Children's HospitalBjoern Peters - La Jolla Institute for Immunology, La Jolla, CA 92037, USANadine Rouphael - Emory and Henry CollegeRuth R Montgomery - Yale School of MedicineElaine Reed - University of California, Los AngelesJoanna Schaenman - University of California, Los AngelesHanno Steen - Boston Children's HospitalOfer Levy - Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USAJoann Diray-Arce - Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USACharles R Langelier - Chan Zuckerberg Biohub San FranciscoIMPACC Network
- Publication Details
- Science translational medicine, v 16(743)
- Publisher
- American Association for the Advancement of Science (AAAS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:001250302200001
- Scopus ID
- 2-s2.0-85190872401
- Other Identifier
- 991021868718904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology
- Medicine, Research & Experimental