Evaluation of the host immune response assay SeptiCyte RAPID for potential triage of COVID-19 patients.

Tools for the evaluation of COVID-19 severity would help clinicians with triage decisions, especially the decision whether to admit to ICU. The aim of this study was to evaluate SeptiCyte RAPID, a host immune response assay (Immunexpress, Seattle USA) as a triaging tool for COVID-19 patients requiring hospitalization and potentially ICU care. SeptiCyte RAPID employs a host gene expression signature consisting of the ratio of expression levels of two immune related mRNAs, PLA2G7 and PLAC8, measured from whole blood samples. Blood samples from 146 adult SARS-CoV-2 (+) patients were collected within 48 h of hospital admission in PAXgene blood RNA tubes at Hospital del Mar, Barcelona, Spain, between July 28th and December 1st, 2020. Data on demographics, vital signs, clinical chemistry parameters, radiology, interventions, and SeptiCyte RAPID were collected and analyzed with bioinformatics methods. The performance of SeptiCyte RAPID for COVID-19 severity assessment and ICU admission was evaluated, relative to the comparator of retrospective clinical assessment by the Hospital del Mar clinical care team. In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity: critical vs. mild (AUC = 0.93, p < 0.0001), critical vs. moderate (AUC = 0.77, p = 0.002), severe vs. mild (AUC = 0.85, p = 0.0003), severe vs. moderate (AUC = 0.63, p = 0.05). This discrimination was significantly better (by AUC or p-value) than could be achieved by CRP, lactate, creatine, IL-6, or D-dimer. Some of the critical or severe cases had "early" blood draws (before ICU admission; n = 33). For these cases, when compared to moderate and mild cases not in ICU (n = 37), SeptiCyte RAPID had AUC = 0.78 (p = 0.00012). In conclusion, SeptiCyte RAPID was able to stratify COVID-19 cases according to clinical severity as defined by the WHO COVID-19 Clinical Management Living Guidance of January 25th, 2021. Measurements taken early (before a patient is considered for ICU admission) suggest that high SeptiScores could aid in predicting the need for later ICU admission.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.

Global Distribution Patterns of Carbapenemase-Encoding Bacteria in a New Light: Clues on a Role for Ethnicity.

Antibiotic resistance represents a major global concern. The rapid spread of opportunistically pathogenic carbapenemase-encoding bacteria (CEB) requires clinicians, researchers, and policy-makers to swiftly find solutions to reduce transmission rates and the associated health burden. Epidemiological data is key to planning control measures. Our study aims to contribute by providing an analysis of 397 unique CEB isolates detected in a tertiary hospital in Germany. We propose new findings on demographic variables to support preventive sanitary precautions in routine clinical practice. Data on detected CEB was combined with patient's demographic and clinical information for each isolate. Multiple regression techniques were applied to estimate the predictive quality of observed differences. Our findings confirm the role of age and gender in CEB colonization patterns and indicate a role for ethnicity and domicile. Also, carbapenemase-encoding A. baumannii was most frequently introduced to the hospital, while the risk of colonization with VIM-encoding P. aeruginosa rose with the length of hospital stay. P. aeruginosa remains an important complication of prolonged hospital stays. The strong link to hospital-wastewater may have implications for hospital-built environments. A. baumannii can be efficiently controlled from spreading at hospital admission. OXA-encoding CEB being harder to detect in routine screening, targeted preventive measures, such as culture media selective for carbapenem-resistant bacteria, would be opportune for patients from selected regions. The CEB differences linked to ethnicity found in our study may further be supporting the tailoring of diagnostic approaches, as well as health policies upon confirmation by other studies and a better understanding of their global distribution.

Multicenter Evaluation of the QIAstat-Dx Respiratory Panel for Detection of Viruses and Bacteria in Nasopharyngeal Swab Specimens.

The QIAstat-Dx Respiratory Panel (QIAstat-Dx RP) is a multiplex in vitro diagnostic test for the qualitative detection of 20 pathogens directly from nasopharyngeal swab (NPS) specimens. The assay is performed using a simple sample-to-answer platform with results available in approximately 69 min. The pathogens identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus A and B, influenza A, influenza A H1, influenza A H3, influenza A H1N1/2009, influenza B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, rhinovirus/enterovirus, respiratory syncytial virus A and B, Bordetella pertussis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae This multicenter evaluation provides data obtained from 1,994 prospectively collected and 310 retrospectively collected (archived) NPS specimens with performance compared to that of the BioFire FilmArray Respiratory Panel, version 1.7. The overall percent agreement between QIAstat-Dx RP and the comparator testing was 99.5%. In the prospective cohort, the QIAstat-Dx RP demonstrated a positive percent agreement of 94.0% or greater for the detection of all but four analytes: coronaviruses 229E, NL63, and OC43 and rhinovirus/enterovirus. The test also demonstrated a negative percent agreement of ≥97.9% for all analytes. The QIAstat-Dx RP is a robust and accurate assay for rapid, comprehensive testing for respiratory pathogens.

Multicenter evaluation of the QIAstat Respiratory Panel-A new rapid highly multiplexed PCR based assay for diagnosis of acute respiratory tract infections.

Acute respiratory tract infections (ARTI), including the common cold, pharyngitis, sinusitis, otitis media, bronchiolitis and pneumonia are the most common diagnoses among patients seeking medical care in western countries, and account for most antibiotic prescriptions. While a confirmed and fast ARTI diagnosis is key for antibiotic prescribing, empiric antimicrobial treatment remains common, because viral symptoms are often clinically similar and difficult to distinguish from those caused by bacteria. As a result, inappropriate antibiotic prescriptions are high and in certain settings likely higher than the commonly estimated 30%. The QIAstat Respiratory Panel® assay (QIAstat RP) is a multiplexed in vitro diagnostics test for the rapid simultaneous detection of 21 pathogens directly from respiratory samples, including human mastadenovirus A-G, primate bocaparvovirus 1+2, human coronavirus (HKU1, NL63, OC43, 229E), human metapneumovirus A/B, rhinovirus/enterovirus, influenza A virus (no subtype, subtype H1, H1N1/2009, H3), influenza B virus, human respirovirus 1+3, human orthorubulavirus 2+4, human orthopneumovirus, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. We describe the first multicenter study of 445 respiratory samples, collected through the 2016-2017 and 2018 respiratory seasons, with performance compared against BioFire FilmArray RP v1.7 and discrepancy testing by Seegene Allplex RP. The QIAstat RP demonstrated a positive percentage of agreement of 98.0% (95% CI: 96.0-99.1%) and a negative percentage agreement of 99.8% (95% CI: 99.6-99.9%). With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship may potentially be achieved.

Multicenter evaluation of the new QIAstat Gastrointestinal Panel for the rapid syndromic testing of acute gastroenteritis.

In acute gastroenteritis (AGE), identification of the infectious agent is important for patient management. Since symptoms do not reliably identify the agent, microbiological diagnostics are important. Conventional methods lack sensitivity and often take days. Multiplex PCR panels offer fast and sensitive alternatives. Our aim was to assess the performance of the new QIAstat Gastrointestinal Panel (GIP) detecting 24 different gastroenteric pathogens from stool in Cary-Blair transport medium (Adenovirus F 40/41, Astrovirus, Norovirus GI/GII, Rotavirus A, Sapovirus, Campylobacter spp., Clostridium difficile, Plesiomonas shigelloides, Salmonella spp., Vibrio cholera, Vibrio parahaemolyticus, Vibrio vulnificus, Yersinia enterocolitica, enteroaggregative Escherichia coli, enteropathogenic E. coli, enterotoxigenic E. coli, Shiga-toxin-producing E. coli (stx1 and stx2) (including specific detection of E. coli O157), Shigella spp./enteroinvasive E. coli, Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica and Giardia lamblia). We tested both prospective (n = 163) and retrospective (n = 222) stool samples sent for routine diagnostics by the QIAstat GIP comparing it to the FDA-approved BioFire FilmArray GIP. Seegene Allplex GIP was used for discrepancy testing. After discrepancy testing, QIAstat GIP detected 447 of 455 pathogens (98.2%, 95% confidence interval (CI) 96.6-99.1%). There were eight false positive detections. Multiple pathogens were detected in 32.5% of positive samples. The QIAstat GIP detected a large range of AGE pathogens with a high sensitivity. It offers an easy-to-use system for GI pathogen detection in stool within 70 min. An advantage of the QIAstat is the availability of cycle threshold (CT) values to aid in interpretation of results.