A case of persistent bacteraemia by Ralstonia mannitolilytica and Ralstonia pickettii in an intensive care unit

The Ralstonia spp. genus is a group of non-fermentative, Gram-negative bacteria often resistant to many antibiotics, which are emerging as opportunistic pathogens frequently associated with infections in hospital settings. We present herein a case of combined R. pickettii and R. mannitolilytica persisting and relapsing bacteraemia, possibly caused by a septic arterial thrombosis secondary to the rupture of an internal carotid artery aneurysm. Microbiology studies showed that both Ralstonia isolates produced biofilm and carried class D oxacillinase genes. When confronted with infections caused by members of the Ralstonia genus, identification to the species level is crucial for correct clinical management, as the two species show different antibiotic susceptibility patterns

Meadow orchards as a good practice example for improving biodiversity in intensive apple orchards

Changes in agricultural land use and management are largely responsible for the current global biodiversity crisis. Addressing this crisis necessitates a change in management practices that are considered to limit biodiversity. Comparing intensive land-use forms with their extensive and traditional counterparts can help define good practice example for integrated conservation. We compare remnants of traditional meadow orchards with intensively managed apple orchards in a mountain region by investigating the multi-taxonomic diversity of seven groups (including vascular plants, wild bees, diurnal butterflies, orthopterans, spiders, birds, and bats) and macro-invertebrates inhabiting four habitat strata (soil, ground-dwelling, herb, and tree layer). Each group and stratum was sampled with a target sampling method. We found a consistent trend of higher abundance, diversity, and presence of threatened species in meadow orchards compared to apple orchards. Specifically, wild bees, butterflies, orthopterans, and birds showed significantly lower diversity in apple orchards across different diversity indices. Furthermore, multi-taxonomic indices of all taxa and most habitat strata followed the same trend, supporting the conclusion that these findings are applicable to the entire orchard ecosystem. We conclude that traditional agroforestry systems, such as meadow orchards, could represent a well-suited good-practice example for integrated biodiversity conservation in the agricultural landscape. Finally, we emphasize the importance of maintaining traditional management practices through effective conservation measures such as subsidies as part of agri-environmental scheme

SARS-CoV-2 Early Screening at the Point of Entry: Travelers From Bangladesh to Italy–July 2020

We report phylogenetic and mutational analysis by NGS of six SARS-CoV-2 strains from patients flying from Bangladesh to Italy (July 2020). Data suggest that no further circulation of such imported strains occurred in Italy, stating the efficacy of early screening at the point of entry and supporting the importance of molecular epidemiology in monitoring the efficacy of control measures

COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Background: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. Methods: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. Results: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. Conclusions: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets

Antiviral and Monoclonal Antibody Combination Therapy in Haematological Patients in the Omicron Era

Immunocompromised (IC) patients are at higher risk for persistent and/or severe SARS-CoV-2 infection caused by different viral variants, with a high case-fatality ratio.1,2 The first persistent SARS-CoV-2 infection (5 months) was reported in 2020 in an IC patient with a long persistence of SARS-CoV-2,3 immediately followed by further reports.2,4 Indeed, the impairment of the immune system changes the natural history of COVID-19. However, no consensus exists on clinical management of IC COVID-19 patients.5 Several reports emphasize the clinical relevance of a combination therapy between small-molecule antivirals (AV) and anti-spike monoclonal antibodies (MoAbs) both in early and prolonged COVID-19 clinical management.6,7 In 2022, tixagevimab/cilgavimab (T/C) MoAb fixed combination was introduced as early therapy for outpatient with COVID-19.8 We describe here a single-center case series of 22 IC COVID-19 in patients with hematological disorders (HD) treated with a combined therapy based on tixagevimab/cilgavimab (T/C) plus small-molecule antivirals (AV), between April 1, 2022, and November 30, 2022

COVID-19: viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets

Molnupiravir increases SARS-CoV-2 genome diversity and complexity: A case-control cohort study

Molnupiravir, an oral direct-acting antiviral effective in vitro against SARS-CoV-2, has been largely employed during the COVID-19 pandemic, since December 2021. After marketing and widespread usage, a progressive increase in SARS-CoV-2 lineages characterized by a higher transition/transversion ratio, a characteristic signature of molnupiravir action, appeared in the Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC) databases. Here, we assessed the drug effects by SARS-CoV-2 whole-genome sequencing on 38 molnupiravir-treated persistently positive COVID-19 outpatients tested before and after treatment. Seventeen tixagevimab/cilgavimab-treated outpatients served as controls. Mutational analyses confirmed that SARS-CoV-2 exhibits an increased transition/transversion ratio seven days after initiation of molnupiravir. Moreover we observed an increased G->A ratio compared to controls, which was not related to apolipoprotein B mRNAediting enzyme, catalytic polypeptide-like (APOBEC) activity. In addition, we demonstrated for the first time an increased diversity and complexity of the viral quasispecies

Temporal intra-host variability of mpox virus genomes in multiple body tissues

Whole-genome sequencing (WGS) has been widely used for the genomic characterization and the phylogenesis of mpox virus (MPXV) 2022 multi-country outbreak. To date, no evidence has been reported on intra-host evolution within samples collected over time from a single patient with long-term infection. Fifty-one samples were collected from five patients at different time points post-symptom onset. All samples were confirmed as MPXV DNA positive, amplified by a multiplexed PCR amplicon, and sequenced by WGS. Complete MPXV genomes were assembled by reference mapping and then aligned to perform phylogenetic and hierarchical clustering analysis. Large intra-host variability was observed among the MPXV genomes sequenced from samples of two immunocompromised with advanced HIV-1 infection patients with prolonged MPXV shedding. Overall, 20 nucleotide mutations were identified in the 32 genomes from HIV patients, differently distributed in samples collected from different tissues and at different time points. No sequence compartmentalization nor variation was observed in the three patients with rapid viral clearance. MPXV exhibits adaptation to changing environments within the infected host and consequently demonstrates tissue compartmentalization. Further studies are needed to elucidate the role of this adaptation in forming a pool of genetic variability and contributing to viral persistence and its clinical implications