The host response in different aetiologies of community-acquired pneumonia
Alex R. Schuurman,
Tom D.Y. Reijnders,
Tjitske S.R. van Engelen,
Valentine Léopold,
Justin de Brabander,
Christine van Linge,
Michiel Schinkel,
Liza Pereverzeva,
Bastiaan W. Haak,
Xanthe Brands,
Maadrika M.N.P. Kanglie,
Inge A.H. van den Berk,
Renée A. Douma,
Daniël R. Faber,
Prabath W.B. Nanayakkara,
Jaap Stoker,
Jan M. Prins,
Brendon P. Scicluna,
W. Joost Wiersinga,
Tom van der Poll
Affiliations
Alex R. Schuurman
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Tom D.Y. Reijnders
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Tjitske S.R. van Engelen
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Valentine Léopold
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Anaesthesiology and Intensive Care, GH St Louis-Lariboisière, Inserm UMR-S 942 (MASCOT), Université de Paris, 75010 Paris, France
Justin de Brabander
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Christine van Linge
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Michiel Schinkel
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Liza Pereverzeva
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Bastiaan W. Haak
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Xanthe Brands
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands
Maadrika M.N.P. Kanglie
Department of Radiology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
Inge A.H. van den Berk
Department of Radiology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
Renée A. Douma
Department of Internal Medicine, Flevo Hospital, Almere, the Netherlands
Daniël R. Faber
Department of Internal Medicine, BovenIJ Hospital, Amsterdam, the Netherlands
Prabath W.B. Nanayakkara
Department of Internal Medicine, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands
Jaap Stoker
Department of Radiology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
Jan M. Prins
Department of Internal Medicine, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands
Brendon P. Scicluna
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Centre for Molecular Medicine and Biobanking, University of Malta, Malta; Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei hospital, University of Malta, Malta
W. Joost Wiersinga
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Internal Medicine, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands
Tom van der Poll
Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Internal Medicine, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands; Corresponding author at: Centre for Experimental and Molecular Medicine (CEMM), Amsterdam University Medical Centres - Location AMC, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, the Netherlands.
Summary: 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.
