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Acute SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa in the nose.

ABSTRACT: Research conducted on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and coronavirus disease 2019 (COVID-19) generally focuses on the systemic host response, especially that generated by severely ill patients, with few studies investigating the impact of acute SARS-CoV-2 at the site of infection. We show that the nasal microbiome of SARS-CoV-2-positive patients (CoV⁺, n = 68) at the time of diagnosis is unique when compared to CoV^- healthcare workers (n = 45) and CoV^- outpatients (n = 21). This shift is marked by an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa, which is also positively associated with viral RNA load. Additionally, we observe a robust host transcriptional response in the nasal epithelia of CoV⁺ patients, indicative of an antiviral innate immune response and neuronal damage. These data suggest that the inflammatory response caused by SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens in the nasal cavity that could contribute to increased incidence of secondary bacterial infections.

SUBMITTER: Rhoades NS

PROVIDER: S-EPMC8361213 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Pseudomonas species are frequent inhabitants of freshwater environments and colonizers of water supply networks via bioadhesion and biofilm formation. P. aeruginosa is the species most commonly associated with human disease, causing a wide variety of infections with links to its presence in freshwater systems. Though several other Pseudomonas species are of ecological and public health importance, little knowledge exists regarding environmental abundances of these species. In the present study, an Illumina-based next-generation sequencing (NGS) approach using Pseudomonas-specific primers targeting the 16S rRNA gene was evaluated and applied to a set of freshwater samples from different environments including a cooling tower sampled monthly during 2 years. Our approach showed high in situ specificity and accuracy. NGS read counts revealed a precise quantification of P. aeruginosa and a good correlation with the absolute number of Pseudomonas genome copies in a validated genus-specific qPCR assay, demonstrating the ability of the NGS approach to determine both relative and absolute abundances of Pseudomonas species and P. aeruginosa. The characterization of Pseudomonas communities in cooling tower water allowed us to identify 43 phylotypes, with P. aeruginosa being the most abundant. A shift existed within each year from a community dominated by phylotypes belonging to P. fluorescens and P. oleovorans phylogenetic groups to a community where P. aeruginosa was highly abundant. Co-occurrence was observed between P. aeruginosa and other phylotypes of P. aeruginosa group as well as the potentially pathogenic species P. stutzeri, but not with phylotypes of the P. fluorescens group, indicating the need to further investigate the metabolic networks and ecological traits of Pseudomonas species. This study demonstrates the potential of deep sequencing as a valuable tool in environmental diagnostics and surveillance of health-related pathogens in freshwater environments.

Project description:Bacterial co-infections increase the severity of respiratory viral infections and are frequent causes of mortality in COVID-19 infected subjects. During the COVID-19 period, especially at the beginning of the pandemic, an inappropriate use of broad-spectrum antibiotic treatments has been frequently described, mainly due to prolonged hospitalization, especially in intensive care unit departments, and the use of immune-suppressive treatments as steroids. This misuse has finally led to the occurrence of infections by multi-drug resistant (MDR) bacteria in hospitalized COVID-19 patients. Although different reports assessed the prevalence of Gram-negative infections in COVID-19 infected patients, scarce data are currently available on bloodstream infections caused by Pseudomonas aeruginosa in hospitalized COVID-19 patients. The aim of our systematic review is to describe data on this specific population and to discuss the possible implications that these co-infections could have in the management of COVID-19 pandemics in the future. We systematically analysed the current literature to find all the relevant articles that describe the occurrence of P. aeruginosa bloodstream infections in COVID-19 patients. We found 40 papers that described in detail P. aeruginosa HAIs-BSI in COVID-19 patients, including 756,067 patients overall. The occurrence of severe infections due to MDR bacteria had a significant impact in the management of hospitalized patients with COVID-19 infections, leading to a prolonged time of hospitalization and to a consequent increase in mortality. In the near future, the increased burden of MDR bacteria due to the COVID-19 pandemic might partially be reduced by maintaining the preventive measures of infection control implemented during the acute phase of the COVID-19 pandemic. Finally, we discuss how the COVID-19 pandemic changed the role of antimicrobial stewardship in healthcare settings, according to the isolation of MDR bacteria and how to restore on a large scale the optimization of antibiotic strategies in COVID-19 patients.

Project description:BackgroundThe detection of pathogens in clinical and environmental samples using high-throughput sequencing (HTS) is often hampered by large amounts of background information, which is especially true for viruses with small genomes. Enormous sequencing depth can be necessary to compile sufficient information for identification of a certain pathogen. Generic HTS combining with in-solution capture enrichment can markedly increase the sensitivity for virus detection in complex diagnostic samples.MethodsA virus panel based on the principle of biotinylated RNA baits was developed for specific capture enrichment of epizootic and zoonotic viruses (VirBaits). The VirBaits set was supplemented by a SARS-CoV-2 predesigned bait set for testing recent SARS-CoV-2-positive samples. Libraries generated from complex samples were sequenced via generic HTS (without enrichment) and afterwards enriched with the VirBaits set. For validation, an internal proficiency test for emerging epizootic and zoonotic viruses (African swine fever virus, Ebolavirus, Marburgvirus, Nipah henipavirus, Rift Valley fever virus) was conducted.ResultsThe VirBaits set consists of 177,471 RNA baits (80-mer) based on about 18,800 complete viral genomes targeting 35 epizootic and zoonotic viruses. In all tested samples, viruses with both DNA and RNA genomes were clearly enriched ranging from about 10-fold to 10,000-fold for viruses including distantly related viruses with at least 72% overall identity to viruses represented in the bait set. Viruses showing a lower overall identity (38% and 46%) to them were not enriched but could nonetheless be detected based on capturing conserved genome regions. The internal proficiency test supports the improved virus detection using the combination of HTS plus targeted enrichment but also points to the risk of cross-contamination between samples.ConclusionsThe VirBaits approach showed a high diagnostic performance, also for distantly related viruses. The bait set is modular and expandable according to the favored diagnostics, health sector, or research question. The risk of cross-contamination needs to be taken into consideration. The application of the RNA-baits principle turned out to be user friendly, and even non-experts can easily use the VirBaits workflow. The rapid extension of the established VirBaits set adapted to actual outbreak events is possible as shown for SARS-CoV-2. Video abstract.

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Acute SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa in the nose.

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