TY - JOUR
T1 - Age-related changes in plasma biomarkers and their association with mortality in COVID-19
AU - Michels, Erik H. A.
AU - Appelman, Brent
AU - Brabander, Justin de
AU - van Amstel, Rombout B. E.
AU - Chouchane, Osoul
AU - van Linge, Christine C. A.
AU - Schuurman, Alex R.
AU - Reijnders, Tom D. Y.
AU - Sulzer, Titia A. L.
AU - Klarenbeek, Augustijn M.
AU - Douma, Renée A.
AU - Bos, Lieuwe D. J.
AU - Wiersinga, W. Joost
AU - Peters-Sengers, Hessel
AU - der Poll, Tom van
N1 - Funding Information: Support statement: E.H.A. Michels, J. de Brabander and C.C.A. van Linge received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 847786 (FAIR). H. Peters-Sengers was supported by the Dutch Kidney Foundation (Kolff grant number 19OK009). O. Chouchane was supported by the Landsteiner Foundation (LSBR 1901). T.D.Y. Reijnders was supported by the research programme “NACTAR”, project “MDR-phage” (grant number 16447), which is financed by the Dutch Research Council (NWO). W.J. Wiersinga was supported by the Talud Foundation (Stichting Talud) for the Amsterdam UMC Corona Research Fund, the Netherlands Organisation for Health Research and Development (ZonMw; TURN-COVID grant number 10430142110001). L.D.J. Bos reports grants from the Dutch Lung Foundation, grants from the Dutch Lung Foundation and Health Holland (Public-Private Partnership grant), grants from the Dutch Lung Foundation (Dirkje Postma Award), grants from the IMI COVID19 initiative, and grants from Amsterdam UMC fellowship. The funders of this study had no role in study design, data collection, data analysis, data interpretation or writing of the report. Funding information for this article has been deposited with the Crossref Funder Registry. Publisher Copyright: Copyright ©The authors 2023.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85166400254&partnerID=8YFLogxK
U2 - https://doi.org/10.1183/13993003.00011-2023
DO - https://doi.org/10.1183/13993003.00011-2023
M3 - Article
C2 - 37080568
SN - 0903-1936
VL - 62
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 1
M1 - 2300011
ER -