SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Rosas-Salazar C, Kimura KS, Shilts MH, Strickland BA, Freeman MH, Wessinger BC, Gupta V, Brown HM, Rajagopala SV, Turner JH, Das SR
Journal
The Journal of allergy and clinical immunology
Year
2021
Keywords:
16S rRNA sequencing, COVID-19, SARS-CoV-2, coronavirus, microbiome, nasal, nasopharynx, respiratory
BACKGROUND: Little is known about the relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the respiratory virus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, and the upper respiratory tract (URT) microbiome. OBJECTIVE: We sought to compare the URT microbiome between SARS-CoV-2-infected and -uninfected adults and to examine the association of SARS-CoV-2 viral load with the URT microbiome during COVID-19. METHODS: We characterized the URT microbiome using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild to moderate COVID-19 and 21 asymptomatic, uninfected controls). In those with COVID-19, we measured SARS-CoV-2 viral load using quantitative reverse transcription PCR. We then examined the association of SARS-CoV-2 infection status and its viral load with the ⍺-diversity, β-diversity, and abundance of bacterial taxa of the URT microbiome. Our main models were all adjusted for age and sex. RESULTS: The observed species index was significantly higher in SARS-CoV-2-infected than in -uninfected adults (β linear regression coefficient = 7.53; 95% CI, 0.17-14.89; P = .045). In differential abundance testing, 9 amplicon sequence variants were significantly different in both of our comparisons, with Peptoniphilus lacrimalis, Campylobacter hominis, Prevotella 9 copri, and an Anaerococcus unclassified amplicon sequence variant being more abundant in those with SARS-CoV-2 infection and in those with high viral load during COVID-19, whereas Corynebacterium unclassified, Staphylococcus haemolyticus, Prevotella disiens, and 2 Corynebacterium_1 unclassified amplicon sequence variants were more abundant in those without SARS-CoV-2 infection and in those with low viral load during COVID-19. CONCLUSIONS: Our findings suggest complex associations between SARS-CoV-2 and the URT microbiome in adults. Future studies are needed to examine how these viral-bacterial interactions can impact the clinical progression, severity, and recovery of COVID-19.
Experiment 1
Needs review
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- 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
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Asymptomatic uninfected controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- COVID-19 patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Confirmed symptomatic mild to moderate COVID-19 patients > age 18, nonhospitalized
- Group 0 sample size Number of subjects in the control (unexposed) group
- 21
- Group 1 sample size Number of subjects in the case (exposed) group
- 38
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 2 weeks
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
- Illumina
Statistical Analysis
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- increased
Signature 1
Needs review
Source: Figure 3B
Description: Differential microbial abundance between non-COVID controls and COVID-19 infected patients
Abundance in Group 1: increased abundance in COVID-19 patients
Revision editor(s): Claregrieve1
Signature 2
Needs review
Source: Figure 3B
Description: Differential microbial abundance between non-COVID controls and COVID-19 infected patients
Abundance in Group 1: decreased abundance in COVID-19 patients
| NCBI | Quality Control | Links |
|---|---|---|
| unclassified Lachnospiraceae | ||
| Neisseria sp. | ||
| Anaerostipes hadrus | ||
| Corynebacterium sp. | ||
| Staphylococcus haemolyticus | ||
| Prevotella disiens |
Revision editor(s): Claregrieve1
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- COVID-19 patients with low viral load
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- COVID-19 patients with high viral load
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Confirmed symptomatic mild to moderate COVID-19 patients > age 18, nonhospitalized, with high viral load (quantitative reverse transcription PCR cycle threshold value
below the median for the detection of SARS-CoV-2 nucleocapside gene region 1)
- 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
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
- Richness Number of species
- unchanged
Signature 1
Needs review
Source: Figure 4b
Description: Differential microbial abundance between COVID-19 patients with high viral load and patients with low viral load
Abundance in Group 1: increased abundance in COVID-19 patients with high viral load
Revision editor(s): Claregrieve1
Signature 2
Needs review
Source: Figure 4b
Description: Differential microbial abundance between COVID-19 patients with high viral load and patients with low viral load
Abundance in Group 1: decreased abundance in COVID-19 patients with high viral load
Revision editor(s): Claregrieve1
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