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 - https://doi.org/10.1016/j.ebiom.2022.104082
DO - https://doi.org/10.1016/j.ebiom.2022.104082
M3 - Article
C2 - 35660785
SN - 2352-3964
VL - 81
JO - eBioMedicine
JF - eBioMedicine
M1 - 104082
ER -