Background Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was... Show moreBackground Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Severity Index (PSI) with clinical and microbiological outcomes in patients with COVID-19 presenting to the emergency department (ED).Methods This is a substudy of a large observational cohort study (PredictED study). The PredictED included adult patients from whom a blood culture was drawn at the ED of Haga Teaching Hospital, The Netherlands. For this substudy, all patients who tested positive for SARS-CoV-2 by PCR in March and April 2020 were included. The primary outcome was the incidence of bacterial coinfection. We used logistic regression analysis for associations of procalcitonin, C reactive protein (CRP), ferritin, lymphocyte count and PSI score with a severe disease course, defined as intensive care unit admission and/or 30-day mortality. The area under the receiver operating characteristics curve (AUC) quantified the discriminatory performance.Results We included 142 SARS-CoV-2 positive patients. On presentation, the median duration of symptoms was 8 days. 41 (29%) patients had a severe disease course and 24 (17%) died within 30 days. The incidence of bacterial coinfection was 2/142 (1.4%). None of the blood cultures showed pathogen growth while 6.3% was contaminated. The AUCs for predicting severe disease were 0.76 (95% CI 0.68 to 0.84), 0.70 (0.61 to 0.79), 0.62 (0.51 to 0.74), 0.62 (0.51 to 0.72) and 0.72 (0.63 to 0.81) for procalcitonin, CRP, ferritin, lymphocyte count and PSI score, respectively.Conclusion Blood cultures appear to have limited value while procalcitonin and the PSI appear to be promising tools in helping physicians identify patients at risk for severe disease course in COVID-19 at presentation to the ED. Show less
The studies described in this thesis have provided novel insight into airway epithelial repair mechanisms and their modulation by cigarette smoke, and insight into mesenchymal stromal cell... Show moreThe studies described in this thesis have provided novel insight into airway epithelial repair mechanisms and their modulation by cigarette smoke, and insight into mesenchymal stromal cell treatment of COPD. We have shown that cigarette smoke delays wound repair in injured airway epithelial cells and that the inflammatory mediators present in the lungs of patients with COPD increase the regenerative potential of MSCs. We have furthermore demonstrated that MSCs from patients with severe COPD can be safely used as a cell-based therapy to treat these patients. Many questions remain regarding route of administration, dosage and timing of MSCs administration in COPD. Useful outcome parameters to assess MSC-mediated effects on lung tissue are largely undetermined, and we propose to include analysis of effects on endothelial and inflammatory cells in future clinical trials. The use of ALI-PBEC and alveolar epithelial cell cultures and ex vivo lung perfusion models will help to advance our understanding of the potential of MSCs in pulmonarydiseases. Parallel developments in other areas of regenerative medicine, including those related to induced pluripotent stem cells and ex vivo organ engineering, will synergistically advance the much awaited therapeutic arsenal that is needed to restore pulmonary function in COPD Show less
Amatngalim, G.D.; Broekman, W.; Daniel, N.M.; Vlugt, L.E.P.M. van der; Schadewijk, A. van; Taube, C.; Hiemstra, P.S. 2016
ABSTRACT Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated forclinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether... Show moreABSTRACT Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated forclinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether COPDaffects BM-MSCs.To investigate this, BM-MSCs from nine COPD patients and nine non-COPD age-matched controls werecompared with regard to immunophenotype, growth and differentiation potential, and migration capacity.Other functional assays included the response to pro-inflammatory stimuli and inducers of the nuclearfactor (erythroid derived 2)-like 2 antioxidant response element (Nrf2-ARE) pathway, and effects on NCIH292airway epithelial cells.No significant differences were observed in terms of morphology, proliferation and migration, except forincreased adipocyte differentiation potential in the COPD group. Both groups were comparable regardingmRNA expression of growth factors and inflammatory mediators, and in their potential to induce mRNAexpression of epidermal growth factor receptor ligands in NCI-H292 airway epithelial cells. MSCs fromCOPD patients secreted more interleukin-6 in response to pro-inflammatory stimuli. Activation of the Nrf2-ARE pathway resulted in a comparable induction of mRNA expression of four target genes, but theexpression of the NAD(P)H:quinone oxidoreductase 1 gene NQO1 was lower in MSCs from COPD patients.The observation that MSCs from COPD patients are phenotypically and functionally comparable tothose from non-COPD controls implies that autologous MSCs can be considered for use in the setting ofclinical trials as a treatment for COPD. Show less
