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

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Reviewed Marked as Reviewed by Folakunmi on 2024-3-25
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Devi P, Maurya R, Mehta P, Shamim U, Yadav A, Chattopadhyay P, Kanakan A, Khare K, Vasudevan JS, Sahni S, Mishra P, Tyagi A, Jha S, Budhiraja S, Tarai B, Pandey R
Journal
Microbiology spectrum
Year
2022
Keywords:
COVID-19, Holo-Seq, co-infection, disease outcome, disease sub-phenotype, host-pathogen interactions, metabolic pathways, nasopharyngeal RNA, pathogen genomics, respiratory virus oligo panel (RVOP), transcriptionally active microbial isolates
The modulators of severe COVID-19 have emerged as the most intriguing features of SARS-CoV-2 pathogenesis. This is especially true as we are encountering variants of concern (VOC) with increased transmissibility and vaccination breakthroughs. Microbial co-infections are being investigated as one of the crucial factors for exacerbation of disease severity and complications of COVID-19. A key question remains whether early transcriptionally active microbial signature/s in COVID-19 patients can provide a window for future disease severity susceptibility and outcome? Using complementary metagenomics sequencing approaches, respiratory virus oligo panel (RVOP) and Holo-seq, our study highlights the possible functional role of nasopharyngeal early resident transcriptionally active microbes in modulating disease severity, within recovered patients with sub-phenotypes (mild, moderate, severe) and mortality. The integrative analysis combines patients' clinical parameters, SARS-CoV-2 phylogenetic analysis, microbial differential composition, and their functional role. The clinical sub-phenotypes analysis led to the identification of transcriptionally active bacterial species associated with disease severity. We found significant transcript abundance of Achromobacter xylosoxidans and Bacillus cereus in the mortality, Leptotrichia buccalis in the severe, Veillonella parvula in the moderate, and Actinomyces meyeri and Halomonas sp. in the mild COVID-19 patients. Additionally, the metabolic pathways, distinguishing the microbial functional signatures between the clinical sub-phenotypes, were also identified. We report a plausible mechanism wherein the increased transcriptionally active bacterial isolates might contribute to enhanced inflammatory response and co-infections that could modulate the disease severity in these groups. Current study provides an opportunity for potentially using these bacterial species for screening and identifying COVID-19 patient sub-groups with severe disease outcome and priority medical care. IMPORTANCE COVID-19 is invariably a disease of diverse clinical manifestation, with multiple facets involved in modulating the progression and outcome. In this regard, we investigated the role of transcriptionally active microbial co-infections as possible modulators of disease pathology in hospital admitted SARS-CoV-2 infected patients. Specifically, can there be early nasopharyngeal microbial signatures indicative of prospective disease severity? Based on disease severity symptoms, the patients were segregated into clinical sub-phenotypes: mild, moderate, severe (recovered), and mortality. We identified significant presence of transcriptionally active isolates, Achromobacter xylosoxidans and Bacillus cereus in the mortality patients. Importantly, the bacterial species might contribute toward enhancing the inflammatory responses as well as reported to be resistant to common antibiotic therapy, which together hold potential to alter the disease severity and outcome.

Experiment 1


Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/08

Curator: Leenaa

Revision editor(s): Svetlana up, Folakunmi, Omojokunoluwatomisin, Leenaa

Subjects

Location of subjects
India
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Nasopharynx Nasenrachenraum,Epipharynx,Nasal part of pharynx,Pars nasalis pharyngis,Rhinopharynx,Nasopharynx,nasopharynx
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
COVID-19 symptoms measurement COVID-19 symptoms measurement,cOVID-19 symptoms measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
mild
Group 1 name Corresponds to the case (exposed) group for case-control studies
moderate
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients showing breathing difficulty with SpO2 levels ranging between 91% and 93%.
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
36

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/08

Curator: Leenaa

Revision editor(s): Leenaa

Source: Figure 3i-j

Description: Differentially abundant bacterial species between mild group and moderate group

Abundance in Group 1: decreased abundance in moderate

NCBI Quality ControlLinks
Halomonas sp.
Schaalia meyeri

Revision editor(s): Leenaa

Experiment 2


Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa, Folakunmi

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
mortality
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who succumbed to COVID-19 during hospital stay
Group 1 sample size Number of subjects in the case (exposed) group
12

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa

Source: Figure 3e

Description: Differentially abundant bacterial species between mild group and mortality group

Abundance in Group 1: increased abundance in mortality

NCBI Quality ControlLinks
Achromobacter xylosoxidans

Revision editor(s): Leenaa

Experiment 3


Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
moderate
Group 1 name Corresponds to the case (exposed) group for case-control studies
severe
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients showing respiratory distress with respiratory support requirement and SpO2 levels < 90%
Group 0 sample size Number of subjects in the control (unexposed) group
36
Group 1 sample size Number of subjects in the case (exposed) group
14

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa

Source: Figure 3g

Description: Differentially abundant bacterial species between moderate group and severe group

Abundance in Group 1: increased abundance in severe

NCBI Quality ControlLinks
Leptotrichia buccalis

Revision editor(s): Leenaa

Experiment 4


Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa, Folakunmi

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
mortality
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients who succumbed to COVID-19 during hospital stay
Group 1 sample size Number of subjects in the case (exposed) group
12

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa

Source: Figure 3f

Description: Differentially abundant bacterial species between moderate group and mortality group

Abundance in Group 1: increased abundance in mortality

NCBI Quality ControlLinks
Bacillus cereus

Revision editor(s): Leenaa

Signature 2

Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa

Source: Figure 3h

Description: Differentially abundant bacterial species between moderate group and mortality group

Abundance in Group 1: decreased abundance in mortality

NCBI Quality ControlLinks
Veillonella parvula

Revision editor(s): Leenaa

Experiment 5


Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa, Folakunmi

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
severe
Group 0 sample size Number of subjects in the control (unexposed) group
14

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Folakunmi on 2024-3-25

Curated date: 2024/03/10

Curator: Leenaa

Revision editor(s): Leenaa

Source: Figure 3g

Description: Differentially abundant bacterial species between severe group and mortality group

Abundance in Group 1: decreased abundance in mortality

NCBI Quality ControlLinks
Leptotrichia buccalis

Revision editor(s): Leenaa