CHEST critical care · 2026
Inflammation, Endothelial Dysfunction, and Frailty Over 3 Years in Survivors of COVID-19 ARDS vs Pneumonia.
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Khan Zain, Jones Ansley E, Gardner William M, McGroder Claire F, Murphy Scarlett O, Depender Christopher, Mira-Sanchez Margarita, Ogunlusi Charity O, Garcia Christine K, Wei Ying, Baldwin Matthew R
Аннотация
BACKGROUND: Inflammation and endothelial dysfunction are associated with increased severity and mortality in COVID-19 ARDS.
RESEARCH QUESTIONS: Do survivors of COVID-19 ARDS show greater inflammation, endothelial dysfunction, and frailty over 3 years compared with survivors of COVID-19 pneumonia?
STUDY DESIGN AND METHODS: We conducted a single-center prospective cohort study of 150 adults hospitalized during the first COVID-19 wave: 101 patients (67%) with ARDS and 49 patients (33%) with pneumonia requiring only nasal cannula oxygen. Participants were assessed at 4 months, 15 months, and 3 years for physical function, the frailty phenotype, and 9 circulating endothelial and inflammatory biomarkers. We tested associations of ARDS with biomarkers and physical function at each follow-up and via novel 3-year time-weighted average modeling of biomarker levels and functional measures by calculating the area under the curve divided by the time between follow-up. Analyses were adjusted for demographics and comorbidities and for multiple comparisons among biomarker classes.
RESULTS: In adjusted analyses, higher growth differentiation factor (GDF)-15 levels at hospital discharge and soluble intracellular adhesion molecule-1 levels were nominally and significantly associated with ARDS, respectively, and higher soluble tumor necrosis factor receptor-1 levels at 3 years was associated nominally with ARDS. Of the 9 biomarkers, only higher GDF-15 levels were associated with ARDS in 3-year time-weighted analyses. Survivors of ARDS showed greater frailty at 4 months and in 3-year time-weighted average models. Of the 9 biomarkers, only GDF-15 at hospital discharge was associated with both ARDS and frailty.
INTERPRETATION: Our results show that survivors of COVID-19 ARDS exhibited higher levels of GDF-15 and sICAM-1 at discharge, as well as greater frailty, compared with survivors of COVID-19 pneumonia, but these distinctions largely converged by 15 months and 3 years of follow-up. Of all the biomarkers tested, only GDF-15 at hospital discharge was associated with subsequent frailty. These findings are preliminary and require validation, but suggest that targeting residual inflammation-related cellular stress at discharge could mitigate after COVID-19 ARDS frailty.
RESEARCH QUESTIONS: Do survivors of COVID-19 ARDS show greater inflammation, endothelial dysfunction, and frailty over 3 years compared with survivors of COVID-19 pneumonia?
STUDY DESIGN AND METHODS: We conducted a single-center prospective cohort study of 150 adults hospitalized during the first COVID-19 wave: 101 patients (67%) with ARDS and 49 patients (33%) with pneumonia requiring only nasal cannula oxygen. Participants were assessed at 4 months, 15 months, and 3 years for physical function, the frailty phenotype, and 9 circulating endothelial and inflammatory biomarkers. We tested associations of ARDS with biomarkers and physical function at each follow-up and via novel 3-year time-weighted average modeling of biomarker levels and functional measures by calculating the area under the curve divided by the time between follow-up. Analyses were adjusted for demographics and comorbidities and for multiple comparisons among biomarker classes.
RESULTS: In adjusted analyses, higher growth differentiation factor (GDF)-15 levels at hospital discharge and soluble intracellular adhesion molecule-1 levels were nominally and significantly associated with ARDS, respectively, and higher soluble tumor necrosis factor receptor-1 levels at 3 years was associated nominally with ARDS. Of the 9 biomarkers, only higher GDF-15 levels were associated with ARDS in 3-year time-weighted analyses. Survivors of ARDS showed greater frailty at 4 months and in 3-year time-weighted average models. Of the 9 biomarkers, only GDF-15 at hospital discharge was associated with both ARDS and frailty.
INTERPRETATION: Our results show that survivors of COVID-19 ARDS exhibited higher levels of GDF-15 and sICAM-1 at discharge, as well as greater frailty, compared with survivors of COVID-19 pneumonia, but these distinctions largely converged by 15 months and 3 years of follow-up. Of all the biomarkers tested, only GDF-15 at hospital discharge was associated with subsequent frailty. These findings are preliminary and require validation, but suggest that targeting residual inflammation-related cellular stress at discharge could mitigate after COVID-19 ARDS frailty.