Evaluation of the NanoCHIP® Infection Control Panel test for direct detection and screening of methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria and vancomycin-resistant Enterococcus (VRE).

PURPOSE: Rapid detection of infection control targets is needed and several bacterial target assays are commercially available. Detection of patients colonized with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae (KPC-CRE), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) comprises an essential part of infection control programs. This study evaluated the performance and feasibility of a novel molecular-based diagnostic screening test, the NanoCHIP(®) Infection Control Panel (ICP) assay (Savyon Diagnostics, Israel), which enables simultaneous detection of KPC-CRE, MRSA and VRE directly from swab samples and compares its sensitivity and specificity to culture. METHODS: Prospective direct swab analysis of 338 (70 CRE, 198 MRSA and 70 VRE) screening swab samples. RESULTS: Including all targets and all valid samples, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the NanoCHIP(®) ICP assay were 91.1, 99.5, 99.1 and 94.9 %, respectively. CONCLUSIONS: As far as we know, this is the first report regarding a single molecular-based system that detects all three targets (CRE-KPC, MRSA and VRE) simultaneously, directly from swab samples, using the same reaction and platform. Overall, the assay was easy to perform, enabling medium- to high-throughput screening. Same day results enable efficient infection control interventions, such as carrier isolation.

Downregulation of CD45 Signaling in COVID-19 Patients Is Reversed by C24D, a Novel CD45 Targeting Peptide.

CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45 signaling pathway. Various studies have demonstrated that also viruses can interfere with the functions of CD45 and that patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are immune-suppressed. Given the similarity between the role of CD45 in viral immune suppression and our findings on TNBC, we hypothesized that the C24D peptide may have a similar "immune-resetting" effect on PBMCs from COVID-19 patients as it did on PBMCs from TNBC patients. We tested this hypothesis by comparing the CD45/TCR intracellular signaling in PBMCs from ten COVID-19 patients vs. PBMCs from ten healthy volunteers. Herein, we report our findings, demonstrating the immune reactivating effect of C24D via the phosphorylation of the tyrosine 505 and 394 in Lck, the tyrosine 493 in ZAP-70 and the tyrosine 172 in VAV-1 proteins in the CD45 signaling pathway. Despite the relatively small number of patients in this report, the results demonstrate that C24D rescued CD45 signaling. Given the central role played by CD45 in the immune system, we suggest CD45 as a potential therapeutic target.