A cross-sectional study on the nasopharyngeal microbiota of individuals with SARS-CoV-2 infection across three COVID-19 waves in India

Background Multiple variants of the SARS-CoV-2 virus have plagued the world through successive waves of infection over the past three years. Independent research groups across geographies have shown that the microbiome composition in COVID-19 positive patients (CP) differs from that of COVID-19 negative individuals (CN). However, these observations were based on limited-sized sample-sets collected primarily from the early days of the pandemic. Here, we study the nasopharyngeal microbiota in COVID-19 patients, wherein the samples have been collected across the three COVID-19 waves witnessed in India, which were driven by different variants of concern. Methods The nasopharyngeal swabs were collected from 589 subjects providing samples for diagnostics purposes at the Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India and subjected to 16s rRNA gene amplicon - based sequencing. Findings We found variations in the microbiota of symptomatic vs. asymptomatic COVID-19 patients. CP showed a marked shift in the microbial diversity and composition compared to CN, in a wave-dependent manner. Rickettsiaceae was the only family that was noted to be consistently depleted in CP samples across the waves. The genera Staphylococcus, Anhydrobacter, Thermus, and Aerococcus were observed to be highly abundant in the symptomatic CP patients when compared to the asymptomatic group. In general, we observed a decrease in the burden of opportunistic pathogens in the host microbiota during the later waves of infection. Interpretation To our knowledge, this is the first analytical cross-sectional study of this scale, which was designed to understand the relation between the evolving nature of the virus and the changes in the human nasopharyngeal microbiota. Although no clear signatures were observed, this study shall pave the way for a better understanding of the disease pathophysiology and help gather preliminary evidence on whether interventions to the host microbiota can help in better protection or faster recovery.

[1]  M. Joshi,et al.  Nasopharyngeal microbiome of COVID-19 patients revealed a distinct bacterial profile in deceased and recovered individuals , 2022, Microbial Pathogenesis.

[2]  N. Xu,et al.  Global prevalence, treatment and outcome of tuberculosis and COVID-19 coinfection: a systematic review and meta-analysis (from November 2019 to March 2021) , 2022, BMJ Open.

[3]  R. Pandey,et al.  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 , 2022, Microbiology spectrum.

[4]  D. Raoult,et al.  Profile of the Nasopharyngeal Microbiota Affecting the Clinical Course in COVID-19 Patients , 2022, Frontiers in Microbiology.

[5]  D. Kar,et al.  Prevalence of Elizabethkingia meningoseptica Infections and their Resistant Pattern in Tertiary Care Hospital , 2022, Journal of Pure and Applied Microbiology.

[6]  Fangfang Zhou,et al.  Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions , 2022, Signal Transduction and Targeted Therapy.

[7]  C. Steves,et al.  Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study , 2022, The Lancet.

[8]  A. Skrahina,et al.  Tuberculosis Co-Infection Is Common in Patients Requiring Hospitalization for COVID-19 in Belarus: Mixed-Methods Study , 2022, International journal of environmental research and public health.

[9]  C. Lee,et al.  Nosocomial septicemia in COVID-19 nosocomial K. pneumoniae, A. baumannii, and Elizabethkingia meningoseptica septicemia in a patient of COVID-19 , 2022, Journal of Infection.

[10]  A. Weisz,et al.  NGS analysis of nasopharyngeal microbiota in SARS-CoV-2 positive patients during the first year of the pandemic in the Campania Region of Italy , 2022, Microbial Pathogenesis.

[11]  Yonglin Shi,et al.  Characterization of Altered Oropharyngeal Microbiota in Hospitalized Patients With Mild SARS-CoV-2 Infection , 2022, Frontiers in Cellular and Infection Microbiology.

[12]  H. Tun,et al.  Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events , 2022, Gut.

[13]  E. Gratacós,et al.  Nasopharyngeal microbiota profiling of pregnant women with SARS-CoV-2 infection , 2022, Scientific Reports.

[14]  K. To,et al.  SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with Delta variant in TMPRSS2-expressed cells , 2021, Emerging microbes & infections.

[15]  K. Jani,et al.  Nasopharyngeal microbiome reveals the prevalence of opportunistic pathogens in SARS-CoV-2 infected individuals and their association with host types , 2021, Microbes and Infection.

[16]  P. Rougé,et al.  Man-Specific Lectins from Plants, Fungi, Algae and Cyanobacteria, as Potential Blockers for SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) Coronaviruses: Biomedical Perspectives , 2021, Cells.

[17]  M. Shi,et al.  Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19 , 2021, Synthetic and Systems Biotechnology.

[18]  J. Lavigne,et al.  A New Look at the Genus Solobacterium: A Retrospective Analysis of Twenty-Seven Cases of Infection Involving S. moorei and a Review of Sequence Databases and the Literature , 2021, Microorganisms.

[19]  Mohammad Samir Uzzaman,et al.  SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome with inclusion of pathobionts , 2021, Scientific Reports.

[20]  M. Aguero-Rosenfeld,et al.  SARS‐CoV‐2 antibodies: IgA correlates with severity of disease in early COVID‐19 infection , 2021, Journal of medical virology.

[21]  S. Sadeghi,et al.  Chitin and chitosan as tools to combat COVID-19: A triple approach , 2021, International Journal of Biological Macromolecules.

[22]  Y. Haberman,et al.  SARS-CoV-2 does not have a strong effect on the nasopharyngeal microbial composition , 2021, Scientific Reports.

[23]  Rebecca L. Lamason,et al.  The enigmatic biology of rickettsiae: recent advances, open questions and outlook , 2021, Pathogens and disease.

[24]  G. Castaldo,et al.  Nasopharyngeal Microbiome Signature in COVID-19 Positive Patients: Can We Definitively Get a Role to Fusobacterium periodonticum? , 2021, Frontiers in Cellular and Infection Microbiology.

[25]  M. Copetti,et al.  Investigation of Nasal/Oropharyngeal Microbial Community of COVID-19 Patients by 16S rDNA Sequencing , 2021, International journal of environmental research and public health.

[26]  K. Chow,et al.  Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19 , 2021, Gut.

[27]  T. Fatma,et al.  Exploring algae and cyanobacteria as a promising natural source of antiviral drug against SARS-CoV-2 , 2020, Biomedical Journal.

[28]  M. López-Pérez,et al.  Nasopharyngeal Microbial Communities of Patients Infected With SARS-CoV-2 That Developed COVID-19 , 2020, bioRxiv.

[29]  R. Colwell,et al.  Metagenomic Next-Generation Sequencing of Nasopharyngeal Specimens Collected from Confirmed and Suspect COVID-19 Patients , 2020, mBio.

[30]  S. Khatiwada,et al.  Lung microbiome and coronavirus disease 2019 (COVID-19): Possible link and implications , 2020, Human Microbiome Journal.

[31]  M. Farzan,et al.  Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2 , 2020, bioRxiv.

[32]  Zigui Chen,et al.  Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19 , 2020, Gut.

[33]  A. Alnazzawi,et al.  Factors Influencing Global Variations in COVID-19 Cases and Fatalities; A Review , 2020, Healthcare.

[34]  Gavin M Douglas,et al.  PICRUSt2 for prediction of metagenome functions , 2020, Nature Biotechnology.

[35]  Teng Xu,et al.  Metatranscriptomic Characterization of COVID-19 Identified A Host Transcriptional Classifier Associated With Immune Signaling , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[36]  O. Rötzschke,et al.  The role of IgA in COVID-19 , 2020, Brain, Behavior, and Immunity.

[37]  S. Ng,et al.  Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization , 2020, Gastroenterology.

[38]  M. Day.  Covid-19: four fifths of cases are asymptomatic, China figures indicate , 2020, BMJ.

[39]  A. Giacomelli,et al.  Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  Giuliano Rizzardini,et al.  Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study , 2020, Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America.

[41]  J. Ludvigsson.  Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults , 2020, Acta paediatrica.

[42]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[43]  S. Mande,et al.  ‘NetShift’: a methodology for understanding ‘driver microbes’ from healthy and disease microbiome datasets , 2018, The ISME Journal.

[44]  Z. Yuan,et al.  Current knowledge and perspectives of Paenibacillus: a review , 2016, Microbial Cell Factories.

[45]  J. Chun,et al.  Profiling bacterial community in upper respiratory tracts , 2014, BMC Infectious Diseases.

[46]  M. Sale,et al.  Characterization of the nasopharyngeal microbiota in health and during rhinovirus challenge , 2014, Microbiome.

[47]  William A. Walters,et al.  Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample , 2010, Proceedings of the National Academy of Sciences.

[48]  A. Plaut,et al.  Analysis of the immunoglobulin A protease gene of Streptococcus sanguis , 1991, Infection and immunity.

[49]  A. Plaut,et al.  Secretory immunity and the bacterial IgA proteases. , 1981, Reviews of infectious diseases.

[50]  R. Squires.  Depicting , 1969, Philosophy.

[51]  J. Luban.  SARS-CoV-2 , 2020 .

[52]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[53]  I. Saiki,et al.  Anti-viral activity of sulfated chitin derivatives against Friend murine leukaemia and herpes simplex type-1 viruses. , 1993, Vaccine.