Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis.

We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analysed samples of sepsis-suspected patients (N=20) and age-spanning healthy controls (N=12), using flow cytometry-based assays. We measured inflammatory markers from plasma fractions, and immunophenotyped freshly isolated unfixed PBMCs for leukocytes subsets representation and expression of activation markers, including chemokine receptors. We found that beside IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double positive T cells. Post-hoc subgrouping of patients according to their sepsis diagnosis on discharge, identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.

Clinical accuracy of infrared temperature measurement devices: a comparison against non-invasive core-body temperature.

During the coronavirus 2019 (COVID-19) pandemic, the implementation of non-contact infrared thermometry (NCIT) became an increasingly popular method of screening body temperature. However, data on the accuracy of these devices and the standardisation of their use are limited. In the current study, the body temperature of non-febrile volunteers was measured using infrared (IR) thermography, IR tympanic thermometry and IR gun thermometry at different facial feature locations and distances and compared with SpotOn core-body temperature. Poor agreement was found between all IR devices and SpotOn measurements (intra-class correlation coefficient <0.8). Bland-Alman analysis showed the narrowest limits of agreement with the IR gun at 3 cm from the forehead (bias = 0.19°C, limits of agreement (LOA): -0.58°C to 0.97°C) and widest with the IR gun at the nose (bias = 1.40°C, LOA: -1.15°C to 3.94°C). Thus, our findings challenge the established use of IR thermometry devices within hospital settings without adequate standard operating procedures to reduce operator error.

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19.

Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g., IL6, CCL20) or clinical hallmarks of COVID-19 (e.g., neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different center (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19.