Elevated Levels of Anti-Inflammatory Eicosanoids and Monocyte Heterogeneity in Mycobacterium tuberculosis Infection and Disease.

Eicosanoids modulate both innate and adaptive immune responses in Mycobacterium tuberculosis (Mtb) infection and have been suggested as possible Host Directed Therapy (HDT) targets, but more knowledge of eicosanoid dynamics in Mtb infection is required. We investigated the levels and ratios of eicosanoid mediators and their cellular sources, monocyte subsets and CD4 T cells in Tuberculosis (TB) patients with various clinical states of Mtb infection. Patients consenting to prospective enrolment in a TB quality registry and biorepository, 16 with pulmonary TB (before and at-end-of treatment), 14 with extrapulmonary TB and 17 latently infected (LTBI) were included. Plasma levels of Prostaglandin E2 (PGE2), Lipoxin A4 (LXA4), and Leukotriene B4 (LTB4) were measured by enzyme-linked immunosorbent assay. Monocyte subsets and CD4 T cells and their expression of Cyclooxygenase-2 (COX-2), Prostaglandin receptor EP2 (EP2), and 5-Lipoxygenase (5-LOX) were analyzed by flow cytometry with and without Purified Protein Derivate (PPD)-stimulation. Pulmonary TB patients had elevated levels of the anti-inflammatory mediator LXA4 at diagnosis compared to LTBI (p < 0.01), while levels of PGE2 and LTB4 showed no difference between clinical states of Mtb infection. LTB4 was the only mediator to be reduced upon treatment (p < 0.05), along with the ratio LTB4/LXA4 (p < 0.01). Pulmonary TB patients had higher levels of total monocytes at diagnosis compared to end-of-treatment and LTBI (both p < 0.05), and a relative increase in the classical monocyte subset. All monocyte subsets had low basal expression of COX-2 and 5-LOX, which were markedly increased upon PPD stimulation. By contrast, the expression of EP2 was reduced upon stimulation. CD4 T cells expressed low basal COX-2 activity that increased modestly upon stimulation, whereas their basal expression of 5-LOX was considerable. In conclusion, the level of eicosanoids in plasma seem to vary between clinical states of Mtb infection. Mediators in the eicosanoid system are present in monocytes and CD4 T cells. The expression of eicosanoids in monocytes are responsive to mycobacterial stimulation independent of Mtb disease state, but subsets are heterogeneous with regard to eicosanoid-mediator expression. Further exploration of eicosanoid mediators as targets for HDT in TB are warranted.

COVID-19 in an elderly woman with acute functional decline. / Covid-19 påvist hos eldre kvinne med akutt funksjonssvikt.

A woman in her late eighties was referred to Accident and Emergency because of acute functional decline with falls and increasing confusion. SARS-CoV-2 infection was confirmed 48 hours later. Many older people and residents of care homes are vulnerable to functional decline with acute illness. Healthcare professionals should be aware that such symptoms may be due to COVID-19.

Predicting severe COVID-19 in the Emergency Department.

BACKGROUND: COVID-19 may lead to severe disease, requiring intensive care treatment and challenging the capacity of health care systems. The aim of this study was to compare the ability of commonly used scoring systems for sepsis and pneumonia to predict severe COVID-19 in the emergency department. METHODS: Prospective, observational, single centre study in a secondary/tertiary care hospital in Oslo, Norway. Patients were assessed upon hospital admission using the following scoring systems; quick Sequential Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome criteria (SIRS), National Early Warning Score 2 (NEWS2), CURB-65 and Pneumonia Severity index (PSI). The ratio of arterial oxygen tension to inspiratory oxygen fraction (P/F-ratio) was also calculated. The area under the receiver operating characteristics curve (AUROC) for each scoring system was calculated, along with sensitivity and specificity for the most commonly used cut-offs. Severe disease was defined as death or treatment in ICU within 14 days. RESULTS: 38 of 175 study participants developed severe disease, 13 (7%) died and 29 (17%) had a stay at an intensive care unit (ICU). NEWS2 displayed an AUROC of 0.80 (95% confidence interval 0.72-0.88), CURB-65 0.75 (0.65-0.84), PSI 0.75 (0.65-0.84), SIRS 0.70 (0.61-0.80) and qSOFA 0.70 (0.61-0.79). NEWS2 was significantly better than SIRS and qSOFA in predicating severe disease, and with a cut-off of5 points, had a sensitivity and specificity of 82% and 60%, respectively. CONCLUSION: NEWS2 predicted severe COVID-19 disease more accurately than SIRS and qSOFA, but not significantly better than CURB65 and PSI. NEWS2 may be a useful screening tool in evaluating COVID-19 patients during hospital admission. TRIAL REGISTRATION: : ClinicalTrials.gov Identifier: NCT04345536. (https://clinicaltrials.gov/ct2/show/NCT04345536).