Increased Abundance of Achromobacter xylosoxidans and Bacillus cereus in Upper Airway Transcriptionally Active Microbiome of COVID-19 Mortality Patients Indicates Role of Co-Infections in Disease Severity and Outcome

Devi, Priti; Maurya, Ranjeet; Mehta, Priyanka; Shamim, Uzma; Yadav, Aanchal; Chattopadhyay, Partha; Kanakan, Akshay; Khare, Kriti; Vasudevan, Janani Srinivasa; Sahni, Shweta; Mishra, Pallavi; Tyagi, Akansha; Jha, Sujeet; Budhiraja, Sandeep; Tarai, Bansidhar; Pandey, Rajesh

doi:10.1128/spectrum.02311-21

Cited by 17 publications

(19 citation statements)

References 96 publications

(100 reference statements)

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“…In addition, neutrophils may also be responsible for the thrombosis and multi-organ damage of COVID-19 through neutrophil reverse transendothelial migration (rTEM) [51] . Studies have shown that a pre-existing upper respiratory tract viral infection may susceptible the patients to severe bacterial pneumonia and exacerbate the inflammatory response [52] . In this regard, the robust immune response to the SARS-CoV-2 triggers the release of cytokines and a chemokine cascade that results in a hyper-inflammatory state and accumulation of fluid in the lungs [53] , [54] .…”

Section: Resultsmentioning

confidence: 99%

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

Musazadeh

Karimi²,

bagheri³

et al. 2022

Biomedicine & Pharmacotherapy

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Section: Resultsmentioning

confidence: 99%

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

Musazadeh

Karimi²,

bagheri³

et al. 2022

Biomedicine & Pharmacotherapy

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“…The disruption of respiratory and gastrointestinal microbiota homeostasis results in persistent microbiota impairment, directly correlated with the COVID-19 severity. Recent findings have highlighted the microbial signatures for recovered (mild, moderate, and severe) and mortality patients, in Figure 3 (18,51).…”

Section: Sars-cov-2 and Microbiotamentioning

confidence: 99%

“…Even though only the active microorganisms are responsible for the biological functions, the majority of studies in COVID-19 concentrate on identifying the total microbiota rather than the active fraction (108)(109)(110). It is noteworthy that few research groups have attempted to study the transcriptionally active microbial landscape in COVID-19 patients (18,111,112). The study by Devi et al identified the nasopharyngeal microbial signatures associated with the clinical sub-phenotypes of mild, moderate, severe, and mortality in the COVID-19 patients.…”

Section: Sars-cov-2 and Microbiotamentioning

confidence: 99%

“…Although RNA sequencing has made it possible to examine the expressed transcripts of the active members of the microbiome, it still has some experimental and analytical limitations. A significant challenge is the lack of sufficient reference genomes, resulting in an inability to accurately assign and annotate all the sequence reads to the known transcripts for a particular genome/microbe (18). This is also compounded by the fact that the complete culturable condition and functional annotation is known for a very small subset of the microbial community.…”

Section: Introductionmentioning

confidence: 99%

“…Such RNA-based studies on the active microbiome are very limited thus far, including a recent study by our group, wherein we highlighted the significant differential presence of transcriptionally active microbial isolates as possible modulators of COVID-19 disease pathology (18). Given the paucity of evidence regarding the availability of transcriptionally active microbial isolates, we introduce t he term "Transcriptionally active microbes (TAMs)", emphasizing the importance of identifying the active microbial communities.…”

Section: Introductionmentioning

confidence: 99%

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Viral infectious diseases severity: co-presence of transcriptionally active microbes (TAMs) can play an integral role for disease severity

Yadav¹,

Pandey²

2022

Front. Immunol.

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Humans have been challenged by infectious diseases for all of their recorded history, and are continually being affected even today. Next-generation sequencing (NGS) has enabled identification of, i) culture independent microbes, ii) emerging disease-causing pathogens, and iii) understanding of the genome architecture. This, in turn, has highlighted that pathogen/s are not a monolith, and thereby allowing for the differentiation of the wide-ranging disease symptoms, albeit infected by a primary pathogen. The conventional ‘one disease - one pathogen’ paradigm has been positively revisited by considering limited yet important evidence of the co-presence of multiple transcriptionally active microbes (TAMs), potential pathogens, in various infectious diseases, including the COVID-19 pandemic. The ubiquitous microbiota presence inside humans gives reason to hypothesize that the microbiome, especially TAMs, contributes to disease etiology. Herein, we discuss current evidence and inferences on the co-infecting microbes particularly in the diseases caused by the RNA viruses - Influenza, Dengue, and the SARS-CoV-2. We have highlighted that the specific alterations in the microbial taxonomic abundances (dysbiosis) is functionally connected to the exposure of primary infecting pathogen/s. The microbial presence is intertwined with the differential host immune response modulating differential disease trajectories. The microbiota-host interactions have been shown to modulate the host immune responses to Influenza and SARS-CoV-2 infection, wherein the active commensal microbes are involved in the generation of virus-specific CD4 and CD8 T-cells following the influenza virus infection. Furthermore, COVID-19 dysbiosis causes an increase in inflammatory cytokines such as IL-6, TNF-α, and IL-1β, which might be one of the important predisposing factors for severe infection. Through this article, we aim to provide a comprehensive view of functional microbiomes that can have a significant regulatory impact on predicting disease severity (mild, moderate and severe), as well as clinical outcome (survival and mortality). This can offer fresh perspectives on the novel microbial biomarkers for stratifying patients for severe disease symptoms, disease prevention and augmenting treatment regimens.

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Clinical evaluation of a multiplex droplet digital PCR for pathogen detection in critically ill COVID-19 patients with bloodstream infections

Li,

Huang,

Yin

et al. 2023

Infection

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Background Nosocomial bloodstream infections (nBSI) have emerged as a clinical concern for physicians treating COVID-19 patients. In this study, we aimed to evaluate the effectiveness of a multiplex ddPCR in detecting bacterial pathogens in the blood of COVID-19 critically ill patients. Methods This prospective diagnostic study included RT-PCR-confirmed COVID-19 patients admitted to our hospital from December 2022 to February 2023. A multiplex ddPCR assay was used to detect common bacterial pathogens and AMR genes in blood samples of the patients, along with antimicrobial susceptibility testing (AST). The diagnostic performance of the ddPCR assay was evaluated by comparing the results with those obtained through blood culture and clinical diagnosis. Additionally, the ability of ddPCR in detecting bacterial resistance was compared with the AST results. Results Of the 200 blood samples collected from 184 patients, 45 (22.5%) were positive using blood culture, while 113 (56.5%) were positive for bacterial targets using the ddPCR assay. The ddPCR assay outperformed blood culture in pathogen detection rate, mixed infection detection rate, and fungal detection rate. Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens in COVID-19 critically ill patients, followed by Enterococcus and Streptococcus. Compared to blood culture, ddPCR achieved a sensitivity of 75.5%, specificity of 51.0%, PPV of 30.9%, and NPV of 87.8%, respectively. However, there were significant differences in sensitivity among different bacterial species, where Gram-negative bacteria have the highest sensitivity of 90.3%. When evaluated on the ground of clinical diagnosis, the sensitivity, specificity, PPV and NPV of ddPCR were 78.1%, 90.5%, 94.7%, and 65.5%, respectively. In addition, the ddPCR assay detected 23 cases of blaKPC, which shown a better consistent with clinical test results than other detected AMR genes. Compared to blaKPC, there were few other AMR genes detected, indicating that the application of other AMR gene detection in the COVID-19 critically ill patients was limited. Conclusion The multiplex ddPCR assay had a significantly higher pathogen detection positivity than the blood culture, which could be an effective diagnostic tool for BSIs in COVID-19 patients and to improve patient outcomes and reduce the burden of sepsis on the healthcare system, though there is room for optimization of the panels used.- Adjusting the targets to include E. faecalis and E. faecium as well as Candida albicans and Candida glabrata could improve the ddPCR' s effectiveness. However, further research is needed to explore the potential of ddPCR in predicting bacterial resistance through AMR gene detection.

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Increased Abundance of Achromobacter xylosoxidans and Bacillus cereus in Upper Airway Transcriptionally Active Microbiome of COVID-19 Mortality Patients Indicates Role of Co-Infections in Disease Severity and Outcome

Cited by 17 publications

References 96 publications

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

Viral infectious diseases severity: co-presence of transcriptionally active microbes (TAMs) can play an integral role for disease severity

Clinical evaluation of a multiplex droplet digital PCR for pathogen detection in critically ill COVID-19 patients with bloodstream infections

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