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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.

SUBMITTER: Schuurman AR 

PROVIDER: S-EPMC9155985 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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<h4>Background</h4>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.<h4>Methods</h4>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 contro  ...[more]

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2021-08-05 | GSE160329 | GEO