Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology.

Autor: Phan HV; University of California San Francisco, San Francisco, CA 94115, USA., Tsitsiklis A; University of California San Francisco, San Francisco, CA 94115, USA., Maguire CP; University of Texas at Austin, Austin, TX 78712, USA., Haddad EK; Drexel University, Tower Health Hospital, Philadelphia, PA 19104, USA., Becker PM; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., Kim-Schulze S; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Lee B; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Chen J; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Research Computing, Department of Information Technology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Hoch A; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Pickering H; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., van Zalm P; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Altman MC; Benaroya Research Institute, University of Washington, Seattle, WA 98101, USA., Augustine AD; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA., Calfee CS; University of California San Francisco, San Francisco, CA 94115, USA., Bosinger S; Emory School of Medicine, Atlanta, GA 30322, USA., Cairns CB; Drexel University, Tower Health Hospital, Philadelphia, PA 19104, USA., Eckalbar W; University of California San Francisco, San Francisco, CA 94115, USA., Guan L; Yale School of Public Health, New Haven, CT 06510, USA., Jayavelu ND; Benaroya Research Institute, University of Washington, Seattle, WA 98101, USA., Kleinstein SH; Yale School of Medicine, New Haven, CT 06510, USA., Krammer F; Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Maecker HT; Stanford University School of Medicine, Palo Alto, CA 94305, USA., Ozonoff A; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.; Research Computing, Department of Information Technology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Peters B; La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Rouphael N; Emory School of Medicine, Atlanta, GA 30322, USA., Montgomery RR; Yale School of Medicine, New Haven, CT 06510, USA., Reed E; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Schaenman J; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Steen H; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Levy O; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Diray-Arce J; Precision Vaccines Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Langelier CR; University of California San Francisco, San Francisco, CA 94115, USA.; Chan Zuckerberg Biohub San Francisco, San Francisco, CA 94158, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2024 Apr 17; Vol. 16 (743), pp. eadj5154. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1126/scitranslmed.adj5154
Abstrakt: 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.
Databáze: MEDLINE