MicroRNA-223 Dampens Pulmonary Inflammation during Pneumococcal Pneumonia

Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary inflammation in wild-type and microRNA-223-knockout mice was assessed in terms of disease course, histopathology, cellular recruitment and evaluation of inflammatory protein and gene signatures following pneumococcal infection. Low levels of serum microRNA-223 correlated with increased disease severity in pneumococcal pneumonia patients. Prolonged neutrophilic influx into the lungs and alveolar spaces was detected in pneumococci-infected microRNA-223-knockout mice, possibly accounting for aggravated histopathology and acute lung injury. Expression of microRNA-223 in wild-type mice was induced by pneumococcal infection in a time-dependent manner in whole lungs and lung neutrophils. Single-cell transcriptome analyses of murine lungs revealed a unique profile of antimicrobial and cellular maturation genes that are dysregulated in neutrophils lacking microRNA-223. Taken together, low levels of microRNA-223 in human pneumonia patient serum were associated with increased disease severity, whilst its absence provoked dysregulation of the neutrophil transcriptome in murine pneumococcal pneumonia

Mycoplasma pneumoniae

Mycoplasma pneumoniae and Chlamydia spp., which are associated with community-acquired pneumonia (CAP), are difficult to propagate, and can cause clinically indistinguishable disease patterns. During 2011-2012, we used molecular methods to test adult patients in Germany with confirmed CAP for infection with these 2 pathogens. Overall, 12.3% (96/783) of samples were positive for M. pneumoniae and 3.9% (31/794) were positive for Chlamydia spp.; C. psittaci (2.1%) was detected more frequently than C. pneumoniae (1.4%). M. pneumoniae P1 type 1 predominated, and levels of macrolide resistance were low (3.1%). Quarterly rates of M. pneumoniae-positive samples ranged from 1.5% to 27.3%, showing a strong epidemic peak for these infections, but of Chlamydia spp. detection was consistent throughout the year. M. pneumoniae-positive patients were younger and more frequently female, had fewer co-occurring conditions, and experienced milder disease than did patients who tested negative. Clinicians should be aware of the epidemiology of these pathogens in CAP

Analysis of Urinary Glycosaminoglycans to Predict Outcome in COVID-19 and Community-Acquired Pneumonia—A Proof-of-Concept Study

Although coronavirus disease 2019 (COVID-19) is considered a systemic disease associated with vascular inflammation and eventual destruction of the protective endothelial glycocalyx (eGC), biomarkers of eGC damage are not yet available in the clinic. The most prominent components of eGC are sulphated glycosaminoglycans (sGAGs) attached to core proteoglycans. We hypothesised that the amount of sGAG fragments shed in urine (as a surrogate for systemic eGC damage) would correlate with disease severity and outcome. Total urinary sGAG concentration was measured using an in-house optimised 1,9-dimethylmethylene blue (DMMB) assay, which is highly accurate and insensitive to interferences. The median urinary sGAG concentration was significantly higher in 67 hospitalised patients with COVID-19 compared to 72 hospitalised patients with community-acquired pneumonia (CAP). In both groups, urinary sGAG concentrations predicted a combined endpoint (including intubation and death) with an area under the receiver operator characteristic curve of 0.72 (95% CI 0.55–0.88, p = 0.01) and 0.70 (95% CI 0.57–0.83, p = 0.007), respectively. In conclusion, the inexpensive and easy-to-perform DMMB assay provides a surrogate parameter for eGC damage that may be useful for risk stratification of patients with COVID-19 and CAP

Analysis of Urinary Glycosaminoglycans to Predict Outcome in COVID-19 and Community-Acquired Pneumonia—A Proof-of-Concept Study

Although coronavirus disease 2019 (COVID-19) is considered a systemic disease associated with vascular inflammation and eventual destruction of the protective endothelial glycocalyx (eGC), biomarkers of eGC damage are not yet available in the clinic. The most prominent components of eGC are sulphated glycosaminoglycans (sGAGs) attached to core proteoglycans. We hypothesised that the amount of sGAG fragments shed in urine (as a surrogate for systemic eGC damage) would correlate with disease severity and outcome. Total urinary sGAG concentration was measured using an in-house optimised 1,9-dimethylmethylene blue (DMMB) assay, which is highly accurate and insensitive to interferences. The median urinary sGAG concentration was significantly higher in 67 hospitalised patients with COVID-19 compared to 72 hospitalised patients with community-acquired pneumonia (CAP). In both groups, urinary sGAG concentrations predicted a combined endpoint (including intubation and death) with an area under the receiver operator characteristic curve of 0.72 (95% CI 0.55–0.88, p = 0.01) and 0.70 (95% CI 0.57–0.83, p = 0.007), respectively. In conclusion, the inexpensive and easy-to-perform DMMB assay provides a surrogate parameter for eGC damage that may be useful for risk stratification of patients with COVID-19 and CAP