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Published on: October 20, 2023
Age-related changes in plasma biomarkers and their association with mortality in COVID-19
Erik H A Michels1, Brent Appelman2, Justin de Brabander2
1Amsterdam UMC, location University of Amsterdam, Center for Experimental and Molecular Medicine (CEMM), Amsterdam, The Netherlands e.h.michels@amsterdamumc.nl.
Insights
Older adults face higher COVID-19 mortality due to age-related immune changes. Specific biomarkers like soluble tumor necrosis factor receptor 1 are linked to increased mortality in elderly patients with COVID-19.
Area of Science:
- Immunology
- Gerontology
- Infectious Diseases
Background:
- COVID-19 mortality disproportionately affects older individuals.
- Current immunomodulating therapies show limited efficacy in elderly patients.
- The underlying biological mechanisms linking aging, host response, and COVID-19 mortality remain unclear.
Purpose of the Study:
- To investigate the association between aging, host immune response, and mortality in COVID-19 patients.
- To identify specific biomarkers reflecting age-related pathophysiological changes.
- To understand how these changes contribute to increased mortality risk in older adults.
Main Methods:
- Analysis of 43 biomarkers across four pathophysiological domains: endothelial activation, coagulation, inflammation, organ damage, and cytokine release.
- Mediation analysis to link aging-driven host response alterations with 30-day mortality.
- Validation of key biomarkers in intensive care unit and external cohorts.
Main Results:
- Increasing age independently predicted 30-day mortality in COVID-19 patients.
- Aging correlated with heightened endothelial and coagulation activation, inflammation, and organ damage markers, irrespective of comorbidities.
- Soluble tumor necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1, and soluble thrombomodulin significantly mediated the relationship between aging and mortality.
Conclusions:
- Aging profoundly alters the host response to COVID-19, with specific immune modifications contributing to higher mortality in older patients.
- Identified biomarkers offer potential targets for age-specific immunomodulatory interventions.
- Further research into age-related immune dysregulation is warranted for improved COVID-19 treatment strategies.
Background:
Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19.
Methods:
We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort.
Results:
464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively).
Conclusions:
Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19.
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