SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome

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Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15
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


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15

Curated date: 2021/07/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Peace Sandy

Subjects

Location of subjects
United States of America
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 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,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
Symptomatic, mild to moderate 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

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

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15

Curated date: 2021/07/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, Peace Sandy

Source: Figure 3B

Description: Differences in the abundance of taxa of the URT microbiome between adults with and without SARS�CoV-2 infection. Differential abundance testing was conducted using DESeq2 models at the ASV level including age and sex as covariates B, Bar plot depicting the log2 FCs and SEs for ASVs that were significantly different between groups.

Abundance in Group 1: increased abundance in Symptomatic, mild to moderate COVID-19 patients

NCBI Quality ControlLinks
Anaerococcus sp.
Brevundimonas sp.
Campylobacter hominis
Corynebacterium imitans
Corynebacterium sp.
Ezakiella
Granulicatella sp.
Peptoniphilus lacrimalis
Peptoniphilus sp.
Phocaeicola vulgatus
Segatella copri
Sphingobacterium spiritivorum

Revision editor(s): Claregrieve1, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15

Curated date: 2021/07/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, Peace Sandy

Source: Figure 3B

Description: Differences in the abundance of taxa of the URT microbiome between adults with and without SARS�CoV-2 infection. Differential abundance testing was conducted using DESeq2 models at the ASV level including age and sex as covariates B, Bar plot depicting the log2 FCs and SEs for ASVs that were significantly different between groups.

Abundance in Group 1: decreased abundance in Symptomatic, mild to moderate COVID-19 patients

NCBI Quality ControlLinks
Anaerostipes hadrus
Corynebacterium sp.
Neisseria sp.
Prevotella disiens
Staphylococcus haemolyticus
unclassified Lachnospiraceae

Revision editor(s): Claregrieve1, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15

Curated date: 2021/07/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Peace Sandy

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)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15

Curated date: 2021/07/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, Peace Sandy

Source: Figure 4b

Description: Differences in the abundance of taxa of the URT microbiome between SARS-CoV-2–infected adults with and without high viral load (defined as a quantitative reverse transcription PCR cycle threshold value below the median for the detection of SARS-CoV-2 nucleocapside gene region 1 [N1]). Differential abundance testing was conducted using DESeq2 models at the ASV level including age and sex as covariates. B, Bar plot depicting the log2 FCs and SEs for ASVs that were significantly different between groups. The asterisks indicate ASVs that were significantly different between groups and had a consistent direction of association in similar DESeq2 analyses that used a definition of high viral load based on a quan�titative reverse transcription PCR cycle threshold value below the median for the detection of SARS-CoV-2 nucleocapside gene region 2 (N2). The striped bars indicate ASVs that were significantly different between groups and had a consistent direction of association in similar DESeq2 analyses comparing adults with andwithout SARS-CoV-2 infection.

Abundance in Group 1: increased abundance in COVID-19 patients with high viral load

NCBI Quality ControlLinks
Anaerococcus sp.
Campylobacter hominis
Corynebacterium sp.
Enterococcus sp.
Faecalibacterium prausnitzii
Peptoniphilus sp.
Segatella copri
unclassified Enterobacteriaceae
unclassified Neisseriaceae

Revision editor(s): Claregrieve1, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-15

Curated date: 2021/07/10

Curator: Claregrieve1

Revision editor(s): Claregrieve1, Peace Sandy

Source: Figure 4b

Description: Differences in the abundance of taxa of the URT microbiome between SARS-CoV-2–infected adults with and without high viral load (defined as a quantitative reverse transcription PCR cycle threshold value below the median for the detection of SARS-CoV-2 nucleocapside gene region 1 [N1]). Differential abundance testing was conducted using DESeq2 models at the ASV level including age and sex as covariates. B, Bar plot depicting the log2 FCs and SEs for ASVs that were significantly different between groups. The asterisks indicate ASVs that were significantly different between groups and had a consistent direction of association in similar DESeq2 analyses that used a definition of high viral load based on a quan�titative reverse transcription PCR cycle threshold value below the median for the detection of SARS-CoV-2 nucleocapside gene region 2 (N2). The striped bars indicate ASVs that were significantly different between groups and had a consistent direction of association in similar DESeq2 analyses comparing adults with andwithout SARS-CoV-2 infection.

Abundance in Group 1: decreased abundance in COVID-19 patients with high viral load

NCBI Quality ControlLinks
Corynebacterium sp.
Dolosigranulum pigrum
Granulicatella elegans
Neisseria sp.
Prevotella disiens
Staphylococcus haemolyticus
Streptococcus sp.
unclassified Acinetobacter
unclassified Stenotrophomonas

Revision editor(s): Claregrieve1, Peace Sandy