73 Hyperferritinemia in patients with pneumonia deviations reported here in non-critically ill CAP patients stratified according to plasma ferritin levels. Notably, only one patient in the present study had ferritin levels above 4420 ng/ml and the extent of host response dysregulation was much larger in CAP patients on the ICU as compared to CAP patients not requiring intensive care. While elevated circulating ferritin levels are used to select patients for immunomodulatory therapeutic strategies, literature on the pathophysiological implications of hyperferritinemia on the host response during acute infection is scarce. The current investigation taken together with our previous study in critically ill patients [4] suggest that hyperferritinemia identifies CAP patients with a broad deregulation of various key host response mechanisms implicated in the pathogenesis of sepsis, entailing not only systemic inflammation and cytokine release, but also endothelial activation and dysfunction, and activation of the coagulation system. Acknowledgements The authors would like to thank all the subjects who participated in this study, Rosan van der Lee for her aid in pre-processing the stimulation assays, as well as Barbara S. Dierdorp and Tamara Dekker for their help with the workup of the cytokine and plasma biomarker measurements, and the OPTIMACT study group for providing the infrastructure for the OPTIMACT trial. The authors declare no competing interests. This work was supported by a grant from the Netherlands Organization for Health Research and Development [ZonMW; grant number 505300098139 to X.B.]; a personal research grant [AMC PhD scholarship to T.S.R.E.]; a grant from Stichting de Merel [to T.S.R.E.]; a grant from the Dutch Kidney Foundation [Kolff grant number 19OK009 to H.P.S.]; a grant from ZonMW [grant number 40008129814016 to N.A.O.]; the Amsterdam UMC Innovation grant and a ZonMW Health Care Efficiency Program grant [grant number 843001806 for the OPTIMACT trial]. 4
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