Background Brain MRI parenchymal signal abnormalities have been in association with SARS-CoV-2. Purpose Describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe COVI...

Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus pathogenicity. In the last decade, numerous CoNS whole-genome sequences have been released, leading to the identification of numerous putative virulence factors. Koch’s postulates and the molecular rendition of these postulates, established by Stanley Falkow in 1988, do not explain the microbial pathogenicity of CoNS. However, whole-genome sequence data has shed new light on CoNS pathogenicity. In this review, we analyzed the contribution of genomics in defining CoNS virulence, focusing on the most frequent and pathogenic CoNS species: S. epidermidis, S. haemolyticus, S. saprophyticus, S. capitis, and S. lugdunensis.

The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 “critical” (in the intensive care unit under mechanical ventilation) and 25 “non-critical” (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloproteaseADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identifiedADAM9as a driver of disease severity and a candidate therapeutic target.

Cat scratch disease (CSD) is mostly due to Bartonella henselae after inoculation of the organism through a skin injury. Since the causative bacteria cannot be easily cultured from human lymph node samples, the diagnosis usually relies on epidemiological, clinical, histological, and serological criteria (classical criteria). A study was performed to determine the diagnostic value of PCR analysis for the detection of B. henselae for the diagnosis of CSD and its place in the diagnostic strategy alongside the classical criteria. Over a 7-year period, lymph node biopsy specimens or cytopunctures from 70 patients were systematically tested by PCR for the presence of B. henselae DNA ( htrA gene) in the Bacteriology Laboratory of the Hôpitaux Universitaires de Strasbourg. Serological testing by an immunofluorescence assay for B. henselae antibodies was also performed for each patient, and clinical, epidemiological, and histological data were collected. The patients were then divided into two groups according to the number of positive diagnostic criteria for CSD: 29 patients with definite CSD (two or more classical criteria) and 15 patients with possible CSD (less than two classical criteria). The remaining 26 patients for whom another diagnosis was retained were used as a control group. Among all criteria, PCR analysis had the best specificity (100%). The PCR assay for B. henselae was positive for 22 (76%; 95% confidence interval [CI ₉₅ ], 56.5 to 89.7%) of the 29 definite CSD patients and 3 (20%; CI ₉₅ , 4.3 to 48.1%) of the 15 possible CSD patients. We then studied combinations of diagnostic criteria, including B. henselae PCR analysis. The best diagnostic performance was observed if at least two criteria were present among serologic, epidemiologic, histological, and molecular criteria.

Coagulase negative staphylococci (CoNS) are commensal bacteria on human skin. Staphylococcus lugdunensis is a unique CoNS which produces various virulence factors and may, like S. aureus, cause severe infections, particularly in hospital settings. Unlike other staphylococci, it remains highly susceptible to antimicrobials, and genome-based phylogenetic studies have evidenced a highly conserved genome that distinguishes it from all other staphylococci. We demonstrate that S. lugdunensis possesses a closed pan-genome with a very limited number of new genes, in contrast to other staphylococci that have an open pan-genome. Whole-genome nucleotide and amino acid identity levels are also higher than in other staphylococci. We identified numerous genetic barriers to horizontal gene transfer that might explain this result. The S. lugdunensis genome has multiple operons encoding for restriction-modification, CRISPR/Cas and toxin/antitoxin systems. We also identified a new PIN-like domain-associated protein that might belong to a larger operon, comprising a metalloprotease, that could function as a new toxin/antitoxin or detoxification system. We show that S. lugdunensis has a unique genome profile within staphylococci, with a closed pan-genome and several systems to prevent horizontal gene transfer. Its virulence in clinical settings does not rely on its ability to acquire and exchange antibiotic resistance genes or other virulence factors as shown for other staphylococci.

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5–15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5–97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.