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Age-related changes in plasma biomarkers and their association with mortality in COVID-19.

Authors :
Michels EHA
Appelman B
de Brabander J
van Amstel RBE
Chouchane O
van Linge CCA
Schuurman AR
Reijnders TDY
Sulzer TAL
Klarenbeek AM
Douma RA
Bos LDJ
Wiersinga WJ
Peters-Sengers H
van der Poll T
van Agtmael M
Algera AG
Appelman B
van Baarle F
Beudel M
Bogaard HJ
Bomers M
Bonta P
Bos L
Botta M
de Brabander J
de Bree G
de Bruin S
Bugiani M
Bulle E
Buis DTP
Chouchane O
Cloherty A
Dijkstra M
Dongelmans DA
Dujardin RWG
Elbers P
Fleuren L
Geerlings S
Geijtenbeek T
Girbes A
Goorhuis B
Grobusch MP
Hagens L
Hamann J
Harris V
Hemke R
Hermans SM
Heunks L
Hollmann M
Horn J
Hovius JW
de Jong HK
de Jong MD
Koning R
Lemkes B
Lim EHT
van Mourik N
Nellen J
Nossent EJ
Olie S
Paulus F
Peters E
Pina-Fuentes DAI
van der Poll T
Preckel B
Prins JM
Raasveld J
Reijnders T
de Rotte MCFJ
Schinkel M
Schultz MJ
Schrauwen FAP
Schuurman A
Schuurmans J
Sigaloff K
Slim MA
Smeele P
Smit M
Stijnis CS
Stilma W
Teunissen C
Thoral P
Tsonas AM
Tuinman PR
van der Valk M
Veelo DP
Volleman C
de Vries H
Vught LA
van Vugt M
Wouters D
Zwinderman AHK
Brouwer MC
Wiersinga WJ
Vlaar APJ
van de Beek D
Source :
The European respiratory journal [Eur Respir J] 2023 Jul 07; Vol. 62 (1). Date of Electronic Publication: 2023 Jul 07 (Print Publication: 2023).
Publication Year :
2023

Abstract

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.<br />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.<br />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).<br />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.<br />Competing Interests: Conflicts of interest: The authors declare no potential conflicts of interest.<br /> (Copyright ©The authors 2023.)

Details

Language :
English
ISSN :
1399-3003
Volume :
62
Issue :
1
Database :
MEDLINE
Journal :
The European respiratory journal
Publication Type :
Academic Journal
Accession number :
37080568
Full Text :
https://doi.org/10.1183/13993003.00011-2023