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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Upper respiratory virome signatures reflect COVID-19 severity and post-recovery shifts

  • Mudita Gosain1
  • Manjeet Kaur2
  • Daizee Talukdar2
  • Subhash Tanwar2
  • Pradipta Jana2
  • Sonali Porey Karmakar2
  • Jyoti Verma2
  • Susmita Bakshi2
  • Kajal Kamboj2
  • Priyanka Verma2
  • Madhu Pareek2
  • Sreevatsan Raghavan1
6 more authors
  • Pallavi Kshetrapal1
  • Shinjini Bhatnagar1
  • Jayanta Bhattacharya3
  • Pramod Kumar Garg4
  • Nitya Wadhwa1
  • Bhabatosh Das2
4 affiliations
  1. 1Maternal Child Health, BRIC-Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India
  2. 2Microbial Research Centre, BRIC-Translational Health Science and Technology Institute, Faridabad, India
  3. 3Antibody Translational Research Program, Center for Virus Research, BRIC-Translational Health Science and Technology Institute, Faridabad, India
  4. 4Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
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Abstract

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection profoundly affects the upper respiratory tract, yet the dynamics of the resident virome across different stages of Coronavirus Disease 2019 (COVID-19) and recovery remain poorly understood.

Methods: This study profiled alterations in the virome and microbiome in 143 SARS-CoV-2–positive adults, stratified by disease severity (Non-Severe, Severe, Critical), compared with 96 RT-PCR–negative controls. Nasal and oral swabs underwent targeted viral enrichment and next-generation sequencing, followed by virome profiling.

Results: The respiratory virome of SARS-CoV-2-positive individuals was dominated by SARS-CoV-2, with co-detected viruses such as Human Mastadenovirus C, which increased with disease severity and persisting post-recovery. Alpha diversity was highest in Non-Severe cases and declined in Severe and Critical groups, suggesting increasing disruption of the virome with disease severity. Beta diversity showed clear separation between controls and cases, and across severity levels. LEfSe identified distinct viral signatures differentiating infection status, and logistic regression of key viral taxa accurately classified Critical versus post-recovery samples (AUC = 0.91). Although the study focused on viruses, bacterial taxa including Rothia mucilaginosa and Haemophilus parahaemolyticus were also detected with severity-linked variation, highlighting viral–bacterial interactions. Longitudinal paired analysis revealed consistent post-recovery enrichment of Streptococcus-specific bacteriophages across all severity groups, suggesting restoration of Streptococcus-associated phage dynamics during convalescence.

Discussion: Overall, this study reveals SARS-CoV-2–associated alterations in the respiratory virome and microbiome and highlights specific microbial taxa with potential as biomarkers for disease severity and post-infection recovery.

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Cite

BibTeXRIS
BibTeX
@article{gosain2026upper,
  title = {{Upper respiratory virome signatures reflect COVID-19 severity and post-recovery shifts}},
  author = {Mudita Gosain and Manjeet Kaur and Daizee Talukdar and Subhash Tanwar and Pradipta Jana and Sonali Porey Karmakar and Jyoti Verma and Susmita Bakshi and Kajal Kamboj and Priyanka Verma and Madhu Pareek and Sreevatsan Raghavan and Pallavi Kshetrapal and Shinjini Bhatnagar and Jayanta Bhattacharya and Pramod Kumar Garg and Nitya Wadhwa and Bhabatosh Das},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fmicb.2026.1925299},
  url = {https://doi.org/10.3389/fmicb.2026.1925299},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Upper respiratory virome signatures reflect COVID-19 severity and post-recovery shifts
AU  - Mudita Gosain
AU  - Manjeet Kaur
AU  - Daizee Talukdar
AU  - Subhash Tanwar
AU  - Pradipta Jana
AU  - Sonali Porey Karmakar
AU  - Jyoti Verma
AU  - Susmita Bakshi
AU  - Kajal Kamboj
AU  - Priyanka Verma
AU  - Madhu Pareek
AU  - Sreevatsan Raghavan
AU  - Pallavi Kshetrapal
AU  - Shinjini Bhatnagar
AU  - Jayanta Bhattacharya
AU  - Pramod Kumar Garg
AU  - Nitya Wadhwa
AU  - Bhabatosh Das
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1925299
UR  - https://doi.org/10.3389/fmicb.2026.1925299
AB  - Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection profoundly affects the upper respiratory tract, yet the dynamics of the resident virome across different stages of Coronavirus Disease 2019 (COVID-19) and recovery remain poorly understood.  Methods: This study profiled alterations in the virome and microbiome in 143 SARS-CoV-2–positive adults, stratified by disease severity (Non-Severe, Severe, Critical), compared with 96 RT-PCR–negative controls. Nasal and oral swabs underwent targeted viral enrichment and next-generation sequencing, followed by virome profiling.  Results: The respiratory virome of SARS-CoV-2-positive individuals was dominated by SARS-CoV-2, with co-detected viruses such as Human Mastadenovirus C, which increased with disease severity and persisting post-recovery. Alpha diversity was highest in Non-Severe cases and declined in Severe and Critical groups, suggesting increasing disruption of the virome with disease severity. Beta diversity showed clear separation between controls and cases, and across severity levels. LEfSe identified distinct viral signatures differentiating infection status, and logistic regression of key viral taxa accurately classified Critical versus post-recovery samples (AUC = 0.91). Although the study focused on viruses, bacterial taxa including Rothia mucilaginosa and Haemophilus parahaemolyticus were also detected with severity-linked variation, highlighting viral–bacterial interactions. Longitudinal paired analysis revealed consistent post-recovery enrichment of Streptococcus-specific bacteriophages across all severity groups, suggesting restoration of Streptococcus-associated phage dynamics during convalescence.  Discussion: Overall, this study reveals SARS-CoV-2–associated alterations in the respiratory virome and microbiome and highlights specific microbial taxa with potential as biomarkers for disease severity and post-infection recovery.
SN  - 1664-302X
ER  -