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The host response in different aetiologies of community-acquired pneumonia. / Schuurman, Alex R.; Reijnders, Tom D. Y.; van Engelen, Tjitske S. R. et al.

In: EBioMedicine, Vol. 81, 104082, 01.07.2022.

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Schuurman AR, Reijnders TDY, van Engelen TSR, Léopold V, de Brabander J, van Linge C et al. The host response in different aetiologies of community-acquired pneumonia. EBioMedicine. 2022 Jul 1;81:104082. doi: 10.1016/j.ebiom.2022.104082

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@article{9147907b4e854b69a25870414bd2df47,
title = "The host response in different aetiologies of community-acquired pneumonia",
abstract = "Background: Community-acquired pneumonia (CAP) can be caused by a variety of pathogens, of which Streptococcus pneumoniae, Influenza and currently SARS-CoV-2 are the most common. We sought to identify shared and pathogen-specific host response features by directly comparing different aetiologies of CAP. Methods: We measured 72 plasma biomarkers in a cohort of 265 patients hospitalized for CAP, all sampled within 48 hours of admission, and 28 age-and sex matched non-infectious controls. We stratified the biomarkers into several pathophysiological domains- antiviral response, vascular response and function, coagulation, systemic inflammation, and immune checkpoint markers. We directly compared CAP caused by SARS-CoV-2 (COVID-19, n=39), Streptococcus pneumoniae (CAP-strep, n=27), Influenza (CAP-flu, n=22) and other or unknown pathogens (CAP-other, n=177). We adjusted the comparisons for age, sex and disease severity scores. Findings: Biomarkers reflective of a stronger cell-mediated antiviral response clearly separated COVID-19 from other CAPs (most notably granzyme B). Biomarkers reflecting activation and function of the vasculature showed endothelial barrier integrity was least affected in COVID-19, while glycocalyx degradation and angiogenesis were enhanced relative to other CAPs. Notably, markers of coagulation activation, including D-dimer, were not different between the CAP groups. Ferritin was most increased in COVID-19, while other systemic inflammation biomarkers such as IL-6 and procalcitonin were highest in CAP-strep. Immune checkpoint markers showed distinctive patterns in viral and non-viral CAP, with highly elevated levels of Galectin-9 in COVID-19. Interpretation: Our investigation provides insight into shared and distinct pathophysiological mechanisms in different aetiologies of CAP, which may help guide new pathogen-specific therapeutic strategies. Funding: This study was financially supported by the Dutch Research Council, the European Commission and the Netherlands Organization for Health Research and Development.",
keywords = "Aetiology, COVID-19, Community-acquired pneumonia, Host response, Influenza, Streptococcus pneumoniae",
author = "Schuurman, {Alex R.} and Reijnders, {Tom D. Y.} and {van Engelen}, {Tjitske S. R.} and Valentine L{\'e}opold and {de Brabander}, Justin and {van Linge}, Christine and Michiel Schinkel and Liza Pereverzeva and Haak, {Bastiaan W.} and Xanthe Brands and Kanglie, {Maadrika M. N. P.} and {van den Berk}, {Inge A. H.} and Douma, {Ren{\'e}e A.} and Faber, {Dani{\"e}l R.} and Nanayakkara, {Prabath W. B.} and Jaap Stoker and Prins, {Jan M.} and Scicluna, {Brendon P.} and Wiersinga, {W. Joost} and {van der Poll}, Tom",
note = "Funding Information: We would like to thank the Dutch Research Council and the European Commission for their role in funding this study. We would also like to thank the Netherlands Organization for Health Research and Development for funding the OPTIMACT trial, Dutch Trial Register identifier NTR6163. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jul,
day = "1",
doi = "10.1016/j.ebiom.2022.104082",
language = "English",
volume = "81",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - The host response in different aetiologies of community-acquired pneumonia

AU - Schuurman, Alex R.

AU - Reijnders, Tom D. Y.

AU - van Engelen, Tjitske S. R.

AU - Léopold, Valentine

AU - de Brabander, Justin

AU - van Linge, Christine

AU - Schinkel, Michiel

AU - Pereverzeva, Liza

AU - Haak, Bastiaan W.

AU - Brands, Xanthe

AU - Kanglie, Maadrika M. N. P.

AU - van den Berk, Inge A. H.

AU - Douma, Renée A.

AU - Faber, Daniël R.

AU - Nanayakkara, Prabath W. B.

AU - Stoker, Jaap

AU - Prins, Jan M.

AU - Scicluna, Brendon P.

AU - Wiersinga, W. Joost

AU - van der Poll, Tom

N1 - Funding Information: We would like to thank the Dutch Research Council and the European Commission for their role in funding this study. We would also like to thank the Netherlands Organization for Health Research and Development for funding the OPTIMACT trial, Dutch Trial Register identifier NTR6163. Publisher Copyright: © 2022 The Author(s)

PY - 2022/7/1

Y1 - 2022/7/1

N2 - Background: Community-acquired pneumonia (CAP) can be caused by a variety of pathogens, of which Streptococcus pneumoniae, Influenza and currently SARS-CoV-2 are the most common. We sought to identify shared and pathogen-specific host response features by directly comparing different aetiologies of CAP. Methods: We measured 72 plasma biomarkers in a cohort of 265 patients hospitalized for CAP, all sampled within 48 hours of admission, and 28 age-and sex matched non-infectious controls. We stratified the biomarkers into several pathophysiological domains- antiviral response, vascular response and function, coagulation, systemic inflammation, and immune checkpoint markers. We directly compared CAP caused by SARS-CoV-2 (COVID-19, n=39), Streptococcus pneumoniae (CAP-strep, n=27), Influenza (CAP-flu, n=22) and other or unknown pathogens (CAP-other, n=177). We adjusted the comparisons for age, sex and disease severity scores. Findings: Biomarkers reflective of a stronger cell-mediated antiviral response clearly separated COVID-19 from other CAPs (most notably granzyme B). Biomarkers reflecting activation and function of the vasculature showed endothelial barrier integrity was least affected in COVID-19, while glycocalyx degradation and angiogenesis were enhanced relative to other CAPs. Notably, markers of coagulation activation, including D-dimer, were not different between the CAP groups. Ferritin was most increased in COVID-19, while other systemic inflammation biomarkers such as IL-6 and procalcitonin were highest in CAP-strep. Immune checkpoint markers showed distinctive patterns in viral and non-viral CAP, with highly elevated levels of Galectin-9 in COVID-19. Interpretation: Our investigation provides insight into shared and distinct pathophysiological mechanisms in different aetiologies of CAP, which may help guide new pathogen-specific therapeutic strategies. Funding: This study was financially supported by the Dutch Research Council, the European Commission and the Netherlands Organization for Health Research and Development.

AB - Background: Community-acquired pneumonia (CAP) can be caused by a variety of pathogens, of which Streptococcus pneumoniae, Influenza and currently SARS-CoV-2 are the most common. We sought to identify shared and pathogen-specific host response features by directly comparing different aetiologies of CAP. Methods: We measured 72 plasma biomarkers in a cohort of 265 patients hospitalized for CAP, all sampled within 48 hours of admission, and 28 age-and sex matched non-infectious controls. We stratified the biomarkers into several pathophysiological domains- antiviral response, vascular response and function, coagulation, systemic inflammation, and immune checkpoint markers. We directly compared CAP caused by SARS-CoV-2 (COVID-19, n=39), Streptococcus pneumoniae (CAP-strep, n=27), Influenza (CAP-flu, n=22) and other or unknown pathogens (CAP-other, n=177). We adjusted the comparisons for age, sex and disease severity scores. Findings: Biomarkers reflective of a stronger cell-mediated antiviral response clearly separated COVID-19 from other CAPs (most notably granzyme B). Biomarkers reflecting activation and function of the vasculature showed endothelial barrier integrity was least affected in COVID-19, while glycocalyx degradation and angiogenesis were enhanced relative to other CAPs. Notably, markers of coagulation activation, including D-dimer, were not different between the CAP groups. Ferritin was most increased in COVID-19, while other systemic inflammation biomarkers such as IL-6 and procalcitonin were highest in CAP-strep. Immune checkpoint markers showed distinctive patterns in viral and non-viral CAP, with highly elevated levels of Galectin-9 in COVID-19. Interpretation: Our investigation provides insight into shared and distinct pathophysiological mechanisms in different aetiologies of CAP, which may help guide new pathogen-specific therapeutic strategies. Funding: This study was financially supported by the Dutch Research Council, the European Commission and the Netherlands Organization for Health Research and Development.

KW - Aetiology

KW - COVID-19

KW - Community-acquired pneumonia

KW - Host response

KW - Influenza

KW - Streptococcus pneumoniae

UR - http://www.scopus.com/inward/record.url?scp=85132375925&partnerID=8YFLogxK

U2 - 10.1016/j.ebiom.2022.104082

DO - 10.1016/j.ebiom.2022.104082

M3 - Article

C2 - 35660785

VL - 81

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

M1 - 104082

ER -

ID: 25199775