Soluble IL-2R Levels at Baseline Predict the Development of Severe Respiratory Failure and Mortality in COVID-19 Patients.

Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value of soluble interleukin-2 receptor (sIL-2R) for the early identification of patients at risk of developing severe clinical outcomes. sIL-2R levels were measured in 197 patients (60.9% males; median age 61 years; moderate disease, n = 65; severe, n = 132, intubated and/or died, n = 42). All patients received combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) according to our local treatment algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or mortality. Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease, compared with those with moderate disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p = 0.017). sIL-2R was the strongest laboratory predictive factor for intubation/death (hazard ratio 1.749, 95%CI 1.041-2.939, p = 0.035) after adjustment for other known risk factors. Youden's index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative predictive value: 57% and 91%, respectively). Delta sIL-2R between the day of event or discharge minus admission date was higher in patients that intubated/died than in those who did not experience an event (2.91 (10.42) vs. 0.44 (2.88) ng/mL; p = 0.08)). sIL-2R on admission and its dynamic changes during follow-up may reflect disease severity and predict the development of SRF and mortality.

Molecular Basis of Resistance to First-Line Drugs of Mycobacterium tuberculosis/canettii Strains in Greece.

The aim of this study was to determine the rate and the mutations of genes involved to the first-line antituberculous drugs' resistance of M. tuberculosis/canettii isolated in Central Greece from 2010 to 2019. During the study period, the rate of resistance to isoniazid, rifampicin, ethambutol, and pyrazinamide was 5.4%, 0.4%, 1.1%, and 1.1%, respectively. All phenotypically resistant isolates (14 to isoniazid, 3 to ethambutol, 3 to pyrazinamide, and 1 to rifampicin) and 17 susceptible isolates (control group) were tested for the presence of mutations/alterations/polymorphisms by PCR followed by sequencing analysis. The molecular typing of isolates was based on multispacer sequence typing. Despite the phenotypic resistance, mutations were detected in 13 of 21 isolates (11 isoniazid resistant, 1 rifampicin, and 1 pyrazinamide resistant). Four isoniazid-resistant strains carried the most common mutations S315T and C-15T, whereas the remaining seven isolates carried either less known (E399, A162, W477STOP, S94A, G-48A, C-54T, C-17T, L203, A196, S124, and K367) or novel (D74N, G691S, Ains-85, and D171G); none of the susceptible strains was found to be positive for any novel mutation. The two single rifampicin- and pyrazinamide-resistant strains carried the known mutations S450L (also referred as S531L) and L182W, respectively. The presence of uncommon or novel mutations conferring resistance to isoniazid (INH) creates a diagnostic problem in the routine microbiological laboratory, since commercial methods are focused on the detection of the most common mechanisms of resistance (S315T, C-15T, A-16G, T-8C, and T-8A), therefore, fail to detect such strains. The regional differences in the frequencies of mutations associated with resistance to the first-line drugs provide hints for the development of better molecular-based diagnostic tests.

Hepatic brucelloma: a rare complication of a common zoonotic disease.

Hepatic brucelloma (HB), a rare manifestation of brucellosis, refers to liver involvement in the form of abscess. A 35-year-old woman stockbreeder was admitted due to 1-month history of evening fever, sweating and weight loss, while she was on 3-week course of rifampicin/doxycycline for suspected brucellosis. On admission, she had hepatosplenomegaly and a systolic murmur, while cholestasis, increased inflammation markers and a strong-positive Wright-Coombs test were the main laboratory findings. As blood and bone marrow cultures were unrevealing, further investigation with CT imaging showed a central liver calcification surrounded by heterogeneous hypodense area being compatible with HB. Material from CT-guided drainage tested negative for Brucella spp. After failure to improve on a 10-week triple regiment, surgical excision was decided and Brucella spp were identified by PCR. Our case highlights challenges in establishing HB diagnosis, which should be considered on the right epidemiological context and when serological and radiological evidence favour its diagnosis.