tetano
Editor, Senior Moderator
Sci Transl Med
. 2024 Apr 17;16(743):eadj5154.
doi: 10.1126/scitranslmed.adj5154. Epub 2024 Apr 17. Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
Hoang Van Phan[SUP] 1 [/SUP], Alexandra Tsitsiklis[SUP] 1 [/SUP], Cole P Maguire[SUP] 2 [/SUP], Elias K Haddad[SUP] 3 [/SUP], Patrice M Becker[SUP] 4 [/SUP], Seunghee Kim-Schulze[SUP] 5 [/SUP], Brian Lee[SUP] 5 [/SUP], Jing Chen[SUP] 6 7 [/SUP], Annmarie Hoch[SUP] 6 [/SUP], Harry Pickering[SUP] 8 [/SUP], Patrick van Zalm[SUP] 6 [/SUP], Matthew C Altman[SUP] 9 [/SUP], Alison D Augustine[SUP] 4 [/SUP], Carolyn S Calfee[SUP] 1 [/SUP], Steve Bosinger[SUP] 10 [/SUP], Charles B Cairns[SUP] 3 [/SUP], Walter Eckalbar[SUP] 1 [/SUP], Leying Guan[SUP] 11 [/SUP], Naresh Doni Jayavelu[SUP] 9 [/SUP], Steven H Kleinstein[SUP] 12 [/SUP], Florian Krammer[SUP] 5 [/SUP], Holden T Maecker[SUP] 13 [/SUP], Al Ozonoff[SUP] 6 7 [/SUP], Bjoern Peters[SUP] 14 [/SUP], Nadine Rouphael[SUP] 10 [/SUP]; IMPACC Network; Ruth R Montgomery[SUP] 12 [/SUP], Elaine Reed[SUP] 8 [/SUP], Joanna Schaenman[SUP] 8 [/SUP], Hanno Steen[SUP] 6 [/SUP], Ofer Levy[SUP] 6 [/SUP], Joann Diray-Arce[SUP] 6 [/SUP], Charles R Langelier[SUP] 1 15 [/SUP]
Collaborators, Affiliations
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.
. 2024 Apr 17;16(743):eadj5154.
doi: 10.1126/scitranslmed.adj5154. Epub 2024 Apr 17. Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
Hoang Van Phan[SUP] 1 [/SUP], Alexandra Tsitsiklis[SUP] 1 [/SUP], Cole P Maguire[SUP] 2 [/SUP], Elias K Haddad[SUP] 3 [/SUP], Patrice M Becker[SUP] 4 [/SUP], Seunghee Kim-Schulze[SUP] 5 [/SUP], Brian Lee[SUP] 5 [/SUP], Jing Chen[SUP] 6 7 [/SUP], Annmarie Hoch[SUP] 6 [/SUP], Harry Pickering[SUP] 8 [/SUP], Patrick van Zalm[SUP] 6 [/SUP], Matthew C Altman[SUP] 9 [/SUP], Alison D Augustine[SUP] 4 [/SUP], Carolyn S Calfee[SUP] 1 [/SUP], Steve Bosinger[SUP] 10 [/SUP], Charles B Cairns[SUP] 3 [/SUP], Walter Eckalbar[SUP] 1 [/SUP], Leying Guan[SUP] 11 [/SUP], Naresh Doni Jayavelu[SUP] 9 [/SUP], Steven H Kleinstein[SUP] 12 [/SUP], Florian Krammer[SUP] 5 [/SUP], Holden T Maecker[SUP] 13 [/SUP], Al Ozonoff[SUP] 6 7 [/SUP], Bjoern Peters[SUP] 14 [/SUP], Nadine Rouphael[SUP] 10 [/SUP]; IMPACC Network; Ruth R Montgomery[SUP] 12 [/SUP], Elaine Reed[SUP] 8 [/SUP], Joanna Schaenman[SUP] 8 [/SUP], Hanno Steen[SUP] 6 [/SUP], Ofer Levy[SUP] 6 [/SUP], Joann Diray-Arce[SUP] 6 [/SUP], Charles R Langelier[SUP] 1 15 [/SUP]
Collaborators, Affiliations
- PMID: 38630846
- DOI: 10.1126/scitranslmed.adj5154
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.