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Your search keyword '"L.M. Fleuren"' showing total 2 results
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2 results on '"L.M. Fleuren"'

1. Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infectionResearch in context

Author

Lihui Guo, Brent Appelman, Kirsten Mooij-Kalverda, Riekelt H. Houtkooper, Michel van Weeghel, Frédéric M. Vaz, Annemiek Dijkhuis, Tamara Dekker, Barbara S. Smids, Jan Willem Duitman, Marianna Bugiani, Paul Brinkman, Jonne J. Sikkens, H.A. Ayesha Lavell, Rob C.I. Wüst, Michèle van Vugt, René Lutter, M.A. van Agtmael, A.G. Algera, B. Appelman, F.E.H.P. van Baarle, M. Beudel, H.J. Bogaard, M. Bomers, P.I. Bonta, L.D.J. Bos, M. Botta, J. de Brabander, G.J. de Bree, S. de Bruin, M. Bugiani, E.B. Bulle, O. Chouchane, A.P.M. Cloherty, D. Buis, M.C.F.J. de Rotte, M. Dijkstra, D.A. Dongelmans, R.W.G. Dujardin, P.E. Elbers, L.M. Fleuren, S.E. Geerlings, T.B.H. Geijtenbeek, A.R.J. Girbes, A. Goorhuis, M.P. Grobusch, L.A. Hagens, J. Hamann, V.C. Harris, R. Hemke, S.M. Hermans, L.M.A. Heunks, M.W. Hollmann, J. Horn, J.W. Hovius, M.D. de Jong, R. Koing, E.H.T. Lim, N. van Mourik, J.F. Nellen, E.J. Nossent, F. Paulus, E. Peters, D. Piña-Fuentes, T. van der Poll, B. Preckel, J.M. Prins, S.J. Raasveld, T.D.Y. Reijnders, M. Schinkel, F.A.P. Schrauwen, M.J. Schultz, A.R. Schuurman, J. Schuurmans, K. Sigaloff, M.A. Slim, P. Smeele, M.R. Smit, C. Stijnis, W. Stilma, C.E. Teunissen, P. Thoral, A.M. Tsonas, P.R. Tuinman, M. van der Valk, D.P. Veelo, C. Volleman, H. de Vries, L.A. van Vught, M. van Vugt, D. Wouters, A.H. Zwinderman, M.C. Brouwer, W.J. Wiersinga, A.P.J. Vlaar, and D. van de Beek

Subjects
IDO2, PASC, Autophagy, Apoptosis, Kynurenine, Mitochondrial_activity, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology. Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients. Findings: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist. Interpretation: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology. Funding: None.

Published
2023
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2. Lung Microbiota of Critically Ill Patients with COVID-19 Are Associated with Nonresolving Acute Respiratory Distress Syndrome

Author

Robert F. J. Kullberg, Justin de Brabander, Leonoor S. Boers, Jason J. Biemond, Esther J. Nossent, Leo M. A. Heunks, Alexander P. J. Vlaar, Peter I. Bonta, Tom van der Poll, JanWillem Duitman, Lieuwe D. J. Bos, W. Joost Wiersinga, Anno Saris, Heder De Vries, Lilian J. Meijboom, Siebe G. Blok, Alex R. Schuurman, Tom D.Y. Reijnders, Juan J. Garcia Vallejo, Hetty Bontkes, René Lutter, Harm Jan Bogaard, S. de Bruin, R. Koning, M.A. van Agtmael, A.G. Algera, F.E.H.P. van Baarle, D.J.C. Bax, M. Beudel, M. Bomers, M. Botta, G.J. de Bree, M. Bugiani, E.B. Bulle, O. Chouchane, A.P.M. Cloherty, P.E. Elbers, L.M. Fleuren, S.E. Geerlings, B.F. Geerts, T.B.H. Geijtenbeek, A.R.J. Girbes, A. Goorhuis, M.P. Grobusch, F.M.J. Hafkamp, L.A. Hagens, J. Hamann, V.C. Harris, R. Hemke, S.M. Hermans, M.W. Hollmann, J. Horn, J.W. Hovius, M.D. de Jong, N. van Mourik, J.F Nellen, F. Paulus, E. Peters, B. Preckel, S.J. Raasveld, M. Schinkel, M.J. Schultz, K. Sigaloff, M.R. Smit, C. Stijnis, W. Stilma, C.E. Teunissen, P. Thoral, A.M. Tsonas, M. van der Valk, D.P. Veelo, M. van Vugt, D. Wouters, A.H. Zwinderman, M.C. Brouwer, D. van de Beek, Internal medicine, Pulmonary medicine, CCA - Cancer Treatment and quality of life, VU University medical center, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Center of Experimental and Molecular Medicine, Graduate School, Intensive Care Medicine, ACS - Microcirculation, AII - Inflammatory diseases, Pulmonology, Infectious diseases, and 01 Internal and external specialisms

Subjects
Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, Tumor Necrosis Factor-alpha, Critical Illness, Microbiota, host–microbial interactions, COVID-19, Critical Care and Intensive Care Medicine, Respiration, Artificial, RNA, Ribosomal, 16S, Humans, artificial respiration, lung microbiome, Lung
Abstract

Rationale: Bacterial lung microbiota are correlated with lung inflammation and acute respiratory distress syndrome (ARDS) and altered in severe coronavirus disease (COVID-19). However, the association between lung microbiota (including fungi) and resolution of ARDS in COVID-19 remains unclear. We hypothesized that increased lung bacterial and fungal burdens are related to nonresolving ARDS and mortality in COVID-19. Objectives: To determine the relation between lung microbiota and clinical outcomes of COVID-19-related ARDS. Methods: This observational cohort study enrolled mechanically ventilated patients with COVID-19. All patients had ARDS and underwent bronchoscopy with BAL. Lung microbiota were profiled using 16S rRNA gene sequencing and quantitative PCR targeting the 16S and 18S rRNA genes. Key features of lung microbiota (bacterial and fungal burden, α-diversity, and community composition) served as predictors. Our primary outcome was successful extubation adjudicated 60 days after intubation, analyzed using a competing risk regression model with mortality as competing risk. Measurements and Main Results: BAL samples of 114 unique patients with COVID-19 were analyzed. Patients with increased lung bacterial and fungal burden were less likely to be extubated (subdistribution hazard ratio, 0.64 [95% confidence interval, 0.42-0.97]; P = 0.034 and 0.59 [95% confidence interval, 0.42-0.83]; P = 0.0027 per log10 increase in bacterial and fungal burden, respectively) and had higher mortality (bacterial burden, P = 0.012; fungal burden, P = 0.0498). Lung microbiota composition was associated with successful extubation (P = 0.0045). Proinflammatory cytokines (e.g., tumor necrosis factor-α) were associated with the microbial burdens. Conclusions: Bacterial and fungal lung microbiota are related to nonresolving ARDS in COVID-19 and represent an important contributor to heterogeneity in COVID-19-related ARDS.

Published
2022
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