Characteristic of upper respiratory tract microbiota in severe covid-19 adult patients in Indonesia

Angky Budianti; Beti Ernawati Dewi; Tjahjani Mirawati  Sudiro; Leonard Nainggolan; Joedo  Prihartono; Siti Nur Aisyah  Jauharoh; Suhendro  Suwarto; Agus  Sjahrurachman

doi:10.15562/bmj.v12i3.4659

Characteristic of upper respiratory tract microbiota in severe covid-19 adult patients in Indonesia

Angky Budianti ,

Beti Ernawati Dewi ,

Tjahjani Mirawati Sudiro ,

Leonard Nainggolan ,

Joedo Prihartono ,

Siti Nur Aisyah Jauharoh ,

Suhendro Suwarto ,

Agus Sjahrurachman ,

pdf |
DOI: https://doi.org/10.15562/bmj.v12i3.4659 |
Published: 2023-08-11

Abstract

Introduction: Nowadays, new cases of COVID-19 have been found with severe cases and deaths. The upper respiratory microbiota has been associated with susceptibility to viral infection and disease severities. However, the association of respiratory tract microbiota with the modulation of COVID-19 outcomes still raises a question. Therefore, we examined the association between the diversity of upper respiratory microbiota and clinical manifestations of COVID-19.

Methods: This research is an observational cross-sectional study. We characterized the microbiota in the upper airway using the 16S ribosomal RNA sequencing method in 74 COVID-19 patients aged 18-64 years. We also examined the association between COVID-19 severities with alpha and beta diversity of upper respiratory microbiota. The alpha and beta diversity was analyzed by QIIME and shown by R software, AMOVA and MRPP testing was done with R software. The t test and diagrams were performed using R software. Bivariate analysis was carried out by t-test and Chi-square test.

Results: The top five phyla in the upper respiratory tract of Indonesian COVID-19 patients with age 18-64 years old were Firmicutes (32,3%), Bacteroidota (27,1%), Fusobacteriota (15,2%), Proteobacteria (15,1%) and Actinobacteria (7,1%). Shannon and ACE index analysis showed no decline of microbiota diversity in the upper airway with increased disease severity. However, there were significant beta diversity differences in the upper airway microbiota between mild and severe COVID-19. The Firmicutes phylum and Oribacterium genus abundance were significantly higher in severe COVID-19 than in mild. The quantity of the Fusobacteriota phylum, Neisseria, and Fusobacterium genera was significantly higher in mild COVID-19 than in severe.

Conclusion: Our research supports the relationship between the severity of COVID-19 and the diversity of the microbiota in the upper airway in adults. Further studies are needed to examine how microbiota prevents COVID-19 severities.

References

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Man WH, de Steenhuijsen Piters WAA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017;15(5):259–70.
Kumpitsch C, Koskinen K, Schöpf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol. 2019;17(1):87.
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Ventero MP, Moreno-Perez O, Molina-Pardines C, Paytuví-Gallart A, Boix V, Escribano I, et al. Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients. Journal of Infection. 2022;84(3):329–36.
Qin T, Wang Y, Deng J, Xu B, Zhu X, Wang J, et al. Super Dominant Pathobiontic Bacteria in the Nasopharyngeal Microbiota Cause Secondary Bacterial Infection in COVID-19 Patients. Microbiol Spectr. 2022;10(3).
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[1] World Health organization. Clinical management of COVID-19: Interim Guidance. 2020;1–124.

[2] Salzano FA, Marino L, Salzano G, Botta RM, Cascone G, D’Agostino Fiorenza U, et al. Microbiota Composition and the Integration of Exogenous and Endogenous Signals in Reactive Nasal Inflammation. J Immunol Res. 2018;2018:1–17.

[3] Man WH, de Steenhuijsen Piters WAA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017;15(5):259–70.

[4] Kumpitsch C, Koskinen K, Schöpf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol. 2019;17(1):87.

[5] Domínguez-Díaz C, García-Orozco A, Riera-Leal A, Padilla-Arellano JR, Fafutis-Morris M. Microbiota and Its Role on Viral Evasion: Is It With Us or Against Us? Front Cell Infect Microbiol. 2019;9.

[6] Ventero MP, Moreno-Perez O, Molina-Pardines C, Paytuví-Gallart A, Boix V, Escribano I, et al. Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients. Journal of Infection. 2022;84(3):329–36.

[7] Qin T, Wang Y, Deng J, Xu B, Zhu X, Wang J, et al. Super Dominant Pathobiontic Bacteria in the Nasopharyngeal Microbiota Cause Secondary Bacterial Infection in COVID-19 Patients. Microbiol Spectr. 2022;10(3).

[8] Chen J, Liu X, Liu W, Yang C, Jia R, Ke Y, et al. Comparison of the respiratory tract microbiome in hospitalized COVID‐19 patients with different disease severity. J Med Virol. 2022;94(11):5284–93.

[9] Centers for Disease Control and Prevention. Nucleic Acid Amplification Tests (NAATs). National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. 2023.

[10] De Rudder C, Garcia-Tímermans C, De Boeck I, Lebeer S, Van de Wiele T, Calatayud Arroyo M. Lacticaseibacillus casei AMBR2 modulates the epithelial barrier function and immune response in a donor-derived nasal microbiota manner. Sci Rep. 2020;10(1):16939.

[11] Surendra H, Elyazar IR, Djaafara BA, Ekawati LL, Saraswati K, Adrian V, et al. Clinical characteristics and mortality associated with COVID-19 in Jakarta, Indonesia: A hospital-based retrospective cohort study. Lancet Reg Health West Pac. 2021;9:100108.

[12] Mutiawati E, Fahriani M, Mamada SS, Fajar JK, Frediansyah A, Maliga HA, et al. Anosmia and dysgeusia in SARS-CoV-2 infection: incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms - a systematic review and meta-analysis. F1000Res. 2021;10:40.

[13] Gauthier NPG, Locher K, MacDonald C, Chorlton SD, Charles M, Manges AR. Alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity. PLoS One. 2022;17(10):e0275815.

[14] Bose T, Acharya V, Kumar Pinna N, Kaur H, Ranjan M, SaiKrishna J, et al. Composition of nasopharyngeal microbiota in individuals with SARS-CoV-2 infection across three COVID-19 waves in India. bioRvix. 2023;1–40. Available from: https://doi.org/10.1101/2023.01.02.522449

[15] Kolhe R, Sahajpal NS, Vyavahare S, Dhanani AS, Adusumilli S, Ananth S, et al. Alteration in Nasopharyngeal Microbiota Profile in Aged Patients with COVID-19. Diagnostics. 2021;11(9):1622.

[16] Shilts MH, Rosas-Salazar C, Strickland BA, Kimura KS, Asad M, Sehanobish E, et al. Severe COVID-19 Is Associated With an Altered Upper Respiratory Tract Microbiome. Front Cell Infect Microbiol. 2022;11.

[17] Xiong D, Muema C, Zhang X, Pan X, Xiong J, Yang H, et al. Enriched Opportunistic Pathogens Revealed by Metagenomic Sequencing Hint Potential Linkages between Pharyngeal Microbiota and COVID-19. Virol Sin. 2021;36(5):924–33.

[18] Könönen E, Gursoy UK. Oral Prevotella Species and Their Connection to Events of Clinical Relevance in Gastrointestinal and Respiratory Tracts. Front Microbiol. 2022;12.

[19] Hurst JH, McCumber AW, Aquino JN, Rodriguez J, Heston SM, Lugo DJ, et al. Age-Related Changes in the Nasopharyngeal Microbiome Are Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Symptoms Among Children, Adolescents, and Young Adults. Clinical Infectious Diseases. 2022;75(1):e928–37.

[20] Kim JG, Zhang A, Rauseo AM, Goss CW, Mudd PA, O’Halloran JA, et al. The nasopharyngeal and salivary microbiomes in COVID‐19 patients with and without asthma. Allergy. 2022;77(12):3676–9.

[21] Yasir M, Al-Sharif HA, Al-Subhi T, Sindi AA, Bokhary DH, El-Daly MM, et al. Analysis of the nasopharyngeal microbiome and respiratory pathogens in COVID-19 patients from Saudi Arabia. J Infect Public Health. 2023;16(5):680–8.

[22] Fiorito S, Soligo M, Gao Y, Ogulur I, Akdis CA, Bonini S. Is the epithelial barrier hypothesis the key to understanding the higher incidence and excess mortality during COVID‐19 pandemic? The case of Northern Italy. Allergy. 2022;77(5):1408–17.

[23] Candel S, Tyrkalska SD, Álvarez-Santacruz C, Mulero V. The nasopharyngeal microbiome in COVID-19. Emerg Microbes Infect. 2023;12(1).

[24] Korkmaz H, Çetinkol Y, Korkmaz M, Çalgın MK, Kaşko Arıcı Y. Effect of Antibiotic Exposure on Upper Respiratory Tract Bacterial Flora. Medical Science Monitor. 2021;28.

Characteristic of upper respiratory tract microbiota in severe covid-19 adult patients in Indonesia

Abstract

References

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