Genomics of bacterial coinfections from COVID-19 patients: insights into disease severity and antimicrobial resistance

SARS-CoV-2患者经常出现细菌/真菌共感染，这可能会影响疾病的严重程度和死亡率。但合并感染的影响目前尚不清楚。此外，还没有调查世界各地使用抗生素治疗COVID-19感染的不同政策和程序对抗生素耐药性演变的影响。通过提高我们对COVID-19患者细菌合并感染及其对疾病进展的影响的了解，可以制定更明智和改进的方法，以更好地治疗和控制感染。利用来自欧洲和印度各医疗中心的COVID-19细菌感染患者的样本，纳米孔和Illumina技术对迄今为止在试点研究中分离的125种细菌进行了全基因组测序，揭示了多种不同的细菌物种，其中金黄色葡萄球菌和克雷伯氏菌尤为常见。在初步分析中也发现了来自社区和医院获得性的耐多药细菌克隆。此外，对来自个别患者的多个分离株的测序表明，多个克隆引起的感染顺序不同的分离株对抗生素的敏感性不同。这表明在治疗期间出现了抗生素耐药性。该项目将使用群体基因组学和系统遗传学分析从COVID-19患者中分离的细菌菌株，以帮助我们进一步了解疾病严重程度和抗菌素耐药性。旨在探讨COVID-19患者共感染细菌的遗传多样性，以及细菌共感染和特定遗传亚型对COVID-19患者感染严重程度和疾病转归的影响。此外，将研究抗生素耐药性对COVID-19治疗的影响以及合并感染COVID-19患者的细菌的耐药性演变，以帮助优化感染控制并减少抗生素的过度使用，以限制抗生素耐药性的演变。还将探讨社区获得性和医院获得性细菌感染在COVID-19患者中的差异和影响。比较基因组学方法将有助于研究COVID-19共感染细菌的遗传多样性，并了解其起源。此外，它将有助于我们了解细菌之间抗菌素耐药性的演变。这一知识有望改善未来的治疗程序，同时也限制抗菌素耐药性的上升。

Patients with SARS-CoV-2 often present with bacterial/fungal coinfections which can then impact the severity of the disease and mortality. But the impact of coinfections is currently unclear. Additionally, the effect of different policies and procedures regarding antibiotic use to treat COVID-19 infections around the world on the evolution of antibiotic resistance has also not been investigated. By improving our understanding of bacterial coinfections in COVID-19 patients and its impact on disease progression, more informed and improved approaches may be made for better treatment and infection control. Using samples from COVID-19 patients with bacterial infections from various healthcare centres in Europe and India, whole genome sequencing carried out by Nanopore and Illumina technologies on 125 bacterial isolates so far in the pilot study has revealed a wide range of different bacterial species with Staphylococcus aureus and Klebsiella spp. occurring especially frequently. Multidrug resistant bacterial clones originating from community- and hospital- acquired have also been indicated in preliminary analysis. Furthermore, sequencing of multiple isolates from individual patients has suggested multiple clones causing infections with sequential isolates varying in antibiotic sensitivity. This suggests the emergence of antibiotic resistance during treatment. This project will use population genomics and phylogenetics to analyse bacterial strain isolated from COVID-19 patients to help further our understanding of disease severity and antimicrobial resistance. It will aim to investigate the genetic diversity of bacteria causing coinfections in COVID-19 patients and the impact that bacterial coinfections and specific genetic subtypes have on the severity of infections and disease outcome in COVID-19 patients. Moreover, the influence of antibiotic resistance for treatment of COVID-19 and the evolution of antimicrobial resistance in bacteria coinfecting COVID-19 patients will be studied to help optimise infection control and reduce antimicrobial overuse to limit antimicrobial resistance evolution. How community-acquired and hospital-acquired bacterial infections may differ and contribute in COVID-19 patients will also be explored. A comparative genomic approach will allow the genetic diversity of the coinfecting bacteria in COVID-19 to be studied as well as their origins to be understood. In addition, it will help our understanding of the evolution of antimicrobial resistance among bacteria. This knowledge will hopefully improve future treatment procedures while also restricting the rise of antimicrobial resistance.