Oral lesion and microbiome diversity in COVID-19 hospitalized patients

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Alessandra Lunis, Bernal Stewart, Cesar Augusto Migliorati, Ester Cerdeira Sabino, Joyce Vanessa Da Silva Fonseca, Nazareno Scaccia, Pablo Andres Munoz Torres, Paulo Henrique Braz Da Silva, Roberta Pilleggii, Rodrigo Melim Zerbinati, Silvia Figueiredo Costa, Sumatra Melo Da Costa Pereira Jales
Journal
Authorea Inc.
Year
2023
Pages:
16
First page:
1
Keywords:
Brazil, Oral lesion, covid-19, hospitalized patients, sars coronavirus
INTRODUCTION: The oral cavity is an important site for the entry and multiplication of respiratory viruses, and the immune system and oral microbiome act as antiviral barriers. Data regarding oral microbiome and COVID-19 is scarce. Therefore, a prospective cohort was conducted at the Hospital das Clínicas of FMUSP to evaluate the frequency of oral lesions associated with COVID-19 and the diversity of the oral microbiome on disease severity.

METHODS: Oral samples from SARS-CoV-2 positive patients were collected. After DNA extraction from the whole saliva samples, sequencing of the 16S rRNA gene using the Ion Torrent PGM platform was performed. Alpha and beta diversity analyses were conducted using the R program. Clinical data from electronic medical records were collected and multiple logistic regression model was constructed to assess the association between oral microbiome diversity and COVID-19 severity (oxygen therapy, mechanical ventilation). RESULTS: The study included a total of 115 samples from 125 patients, 14 had oral lesions, the majority were female (54.8%), with a mean age of 55.4 years old. Around 59.1% of patients were in intensive care units(ICUs), 87.2% were using antibiotics, and 18.3% died. The most frequently antibiotics used were third-generation cephalosporins(35.7%), piperacillin/tazobactam(27%), and glycopeptides(21.7%). In general, the most abundant phyla were Firmicutes, Proteobacteria, and Bacteroidetes, representing 86.3% of the oral microbiome. Oral microbiome diversity analysis revealed statistical differences in COVID-19 severity (Shannon p=0.05), presence of oral lesions Shannon p=0.05), antibiotic use(Shannon p=0.04), and oxygen therapy Observed p=0.04). Differential abundance analysis identified specific taxa related to each variable, such as Prevotella in severe patients and Staphylococcus in individuals with oral lesions. Multivariable logistic regression pointed out that the SARS-CoV-2 PCR positive on the oral cavity and the age (above 60 years) were risk factors for disease severity. CONCLUSION: Despite the small number of participants with oral cavity lesions, we found significant differences in the microbial communities, particularly in the genus Staphylococcus associated with oral lesions. Although the abundance of Prevotella was associated with severity of COVID-19 on the microbiome analysis, the multivariate model showed that only age and RT-PCR positive for SARS-CoV-2 on the oral cavity were independent risk factors for severity.

Experiment 1


Needs review

Curated date: 2024/03/05

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Subjects

Location of subjects
Brazil
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
Oral cavity Bucca,Buccal cavity,Cavity of mouth,Oral cavity,oral cavity
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Oral ulcer Mouth sore,Mouth ulcer,Oral mucosal ulceration,Oral ulcer,oral ulcer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Covid-19 patients without oral lesions
Group 1 name Corresponds to the case (exposed) group for case-control studies
Covid-19 with oral lesions
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
COVID-19 patients with the presence of oral lesions
Group 0 sample size Number of subjects in the control (unexposed) group
101
Group 1 sample size Number of subjects in the case (exposed) group
14

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Ion Torrent

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
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)?
Yes
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "immunosuppression" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.immunosuppression, Confounders controlled for: "virus detection in saliva (Oral RT-PCR)" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.virus detection in saliva (Oral RT-PCR)

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/06

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Source: Fourth paragraph in section 3.3

Description: Significant difference found in Covid-10 patients who had oral lesions.

Abundance in Group 1: increased abundance in Covid-19 with oral lesions

NCBI Quality ControlLinks
Staphylococcus

Revision editor(s): Nekembe, Aleru Divine

Experiment 2


Needs review

Curated date: 2024/03/07

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Illness severity status Illness severity status,illness severity status
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non severe COVID patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Severe COVID patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
COVID-19 patients with severe symptoms
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/07

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Source: Fourth paragraph in section 3.3

Description: Significant differences found in Covid-10 patients who had severe symptoms.

Abundance in Group 1: increased abundance in Severe COVID patients

NCBI Quality ControlLinks
Prevotella

Revision editor(s): Nekembe, Aleru Divine

Experiment 3


Needs review

Curated date: 2024/03/07

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Antimicrobial agent antibiotic,antibiotics,Antibiotika,Antibiotikum,antibiotique,antimicrobial,antimicrobial agents,microbicide,microbicides,Antimicrobial agent,antimicrobial agent
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No antibiotics use
Group 1 name Corresponds to the case (exposed) group for case-control studies
Antibiotics use
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
COVID-19 patients who had antibiotic therapy in the previous 3 months.

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2024/03/07

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Source: Paragraph 4 in section 3.3 and Paragraph 5 in the discussion section

Description: Significant differences found in Covid-10 patients who were on antibiotic therapy in the previous 3 months.

Abundance in Group 1: increased abundance in Antibiotics use

NCBI Quality ControlLinks
Lactobacillus
Neisseria
Prevotella
Staphylococcus

Revision editor(s): Nekembe, Aleru Divine

Experiment 4


Needs review

Curated date: 2024/03/07

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Oxygen dioxygen,dioxygene,Disauerstoff,InChI=1/O2/c1-2,InChIKey=MYMOFIZGZYHOMD-UHFFFAOYAM,molecular oxygen,O(2),O2,O=O,OXYGEN MOLECULE,Oxygen,oxygen
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No oxygen therapy
Group 1 name Corresponds to the case (exposed) group for case-control studies
Oxygen therapy
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
COVID-19 patients who had oxygen therapy.

Lab analysis

Statistical Analysis

Alpha Diversity

Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2024/03/07

Curator: Nekembe

Revision editor(s): Nekembe, Aleru Divine

Source: Paragraph 4 in section 3.3 and Paragraph 5 in the discussion section

Description: Significant differences found in Covid-10 patients who were on oxygen therapy.

Abundance in Group 1: increased abundance in Oxygen therapy

NCBI Quality ControlLinks
Lactobacillus
Veillonella

Revision editor(s): Nekembe, Aleru Divine

Experiment 5


Needs review

Curated date: 2024/03/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Illness severity status Illness severity status,illness severity status
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non ICU patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
ICU patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
COVID-19 patients who were in intensive care units.

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/03/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Paragraph 4 in section 3.3 and Paragraph 6 in the discussion section

Description: Significant differences found in Covid-10 patients who were in the Intensive Care Unit (ICU).

Abundance in Group 1: increased abundance in ICU patients

NCBI Quality ControlLinks
Lactobacillus
Veillonella

Revision editor(s): Aleru Divine

Signature 2

Needs review

Curated date: 2024/03/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Paragraph 4 in section 3.3 and Paragraph 6 in the discussion section

Description: Significant differences found in Covid-10 patients who were in the Intensive Care Unit (ICU).

Abundance in Group 1: decreased abundance in ICU patients

NCBI Quality ControlLinks
Haemophilus

Revision editor(s): Aleru Divine

Experiment 6


Needs review

Curated date: 2024/03/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Diet Dietary,Diets,Diet,diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non enteral diet
Group 1 name Corresponds to the case (exposed) group for case-control studies
Covid-19 patients on enteral diet
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
COVID-19 patients who were on the enteral diet.

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/03/29

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Paragraph 4 in section 3.3 and Paragraph 6 in the discussion section

Description: Significant differences found in Covid-10 patients who were on enteral diet.

Abundance in Group 1: increased abundance in Covid-19 patients on enteral diet

NCBI Quality ControlLinks
Cardiobacterium
Granulicatella
Haemophilus
Lactobacillus
Leptotrichia
Porphyromonas
Rothia
Streptococcus
Veillonella

Revision editor(s): Aleru Divine