Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease

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dc.citation.articleNumber21125en_US
dc.citation.journalTitleScientific Reportsen_US
dc.citation.volumeNumber12en_US
dc.contributor.authorJochum, Michaelen_US
dc.contributor.authorLee, Michael D.en_US
dc.contributor.authorCurry, Kristenen_US
dc.contributor.authorZaksas, Victoriaen_US
dc.contributor.authorVitalis, Elizabethen_US
dc.contributor.authorTreangen, Todden_US
dc.contributor.authorAagaard, Kjerstien_US
dc.contributor.authorTernus, Krista L.en_US
dc.date.accessioned2023-01-27T14:47:40Zen_US
dc.date.available2023-01-27T14:47:40Zen_US
dc.date.issued2022en_US
dc.description.abstractTo better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host–microbiome–pathogen interactions.en_US
dc.identifier.citationJochum, Michael, Lee, Michael D., Curry, Kristen, et al.. "Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease." <i>Scientific Reports,</i> 12, (2022) Springer Nature: https://doi.org/10.1038/s41598-022-25463-0.en_US
dc.identifier.digitals41598-022-25463-0en_US
dc.identifier.doihttps://doi.org/10.1038/s41598-022-25463-0en_US
dc.identifier.urihttps://hdl.handle.net/1911/114298en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleAnalysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 diseaseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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