ArticlePublisher preview available

Respiratory virome in hospitalized children and analysis of its correlation with disease severity

Authors:
Jing Liao
Jing Liao
Jing Liao
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Jian Hua Wei
Jian Hua Wei
Jian Hua Wei
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Jiao Liu
Jiao Liu
Jiao Liu
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Luo Ren at University College London
Luo Ren
Show all 6 authorsHide
Read publisher preview
Download citation
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Purpose To investigate the composition of respiratory viromes and their association with disease severity among hospitalized pediatric patients. Methods Clinical data and metagenomic next-generation sequencing (mNGS) results were collected from pediatric patients hospitalized at the Children’s Hospital of Chongqing Medical University between January 2022 and September 2023. The analyzed specimens included sputum and bronchoalveolar lavage fluid (BALF). Results The study included 229 patients (65.07% male, median age 3 years) with 25 sputum and 204 BALF samples, of whom 40.17% met the WHO criteria for severe acute respiratory infection (SARI). Herpesviruses were detected in 166 cases (72.49%), including 85 cases of cytomegalovirus (CMV), 64 cases of Epstein-Barr virus (EBV), 34 cases of human herpesvirus-7 (HHV-7), 12 cases of human herpesvirus-6 (HHV-6), and 6 cases of herpes simplex virus type 1 (HSV-1). Additionally, 53 cases of torque teno virus (TTV) and 7 cases of torque teno mini virus (TLMV) were detected. CMV prevalence was highest in neonates, while EBV peaked in the 3–6 year group (37.78%). HSV-1 and HHV-6 were predominantly identified in severe infections. Conclusion Herpesviruses, particularly CMV and EBV, were the most frequently detected viruses, followed by anelloviruses. The age-specific viral distribution patterns provide novel epidemiological perspectives for understanding pediatric respiratory pathogenesis, though their clinical significance requires validation through mechanistic studies. Clinical trial number Not applicable.
Figures - available from: European Journal of Clinical Microbiology & Infectious Diseases
This content is subject to copyright. Terms and conditions apply.
A preview of this full-text is provided by Springer Nature.
Learn more
Content available from European Journal of Clinical Microbiology & Infectious Diseases
This content is subject to copyright. Terms and conditions apply.
RESEARCH
European Journal of Clinical Microbiology & Infectious Diseases
https://doi.org/10.1007/s10096-025-05140-6
CMV Cytomegalovirus
COPD Chronic Obstructive Pulmonary Disease
EBV Epstein-Barr Virus
HCoV Human Coronavirus
HHV-6 Human Herpesvirus-6
HHV-7 Human Herpesvirus-7
HSV-1 Herpes Simplex Virus Type 1
HSV-2 Herpes Simplex Virus Type 2
mNGS Metagenomic Next-Generation Sequencing
NK Natural Killer
NPA Nasopharyngeal Aspirates
PMDB Pathogens Metagenomics Database
TLMV Torque Teno Mini Virus
TTMDV Torque Teno Minivirus
TTMV Torque Teno Midi Virus
TTV Torque Teno Virus
Abbreviations
BALF Bronchoalveolar Lavage Fluid
BPD Bronchopulmonary Dysplasia
CF Cystic Fibrosis
Na Zang
zangna1214@126.com
Enmei Liu
emliu186@126.com
1 Department of Respiratory Medicine of Children’s Hospital
of Chongqing Medical University, National Clinical
Research Center for Child Health and Disorders, Ministry
of Education Key Laboratory of Child Development and
Disorders, Children’s Hospital of Chongqing Medical
University, 136 Zhongshan Second Road, Yuzhong District,
Chongqing 400014, China
2 Chongqing Key Laboratory of Child Rare Diseases in
Infection and Immunity, Chongqing, China
Abstract
Purpose To investigate the composition of respiratory viromes and their association with disease severity among hospital-
ized pediatric patients.
Methods Clinical data and metagenomic next-generation sequencing (mNGS) results were collected from pediatric patients
hospitalized at the Children’s Hospital of Chongqing Medical University between January 2022 and September 2023. The
analyzed specimens included sputum and bronchoalveolar lavage uid (BALF).
Results The study included 229 patients (65.07% male, median age 3 years) with 25 sputum and 204 BALF samples, of
whom 40.17% met the WHO criteria for severe acute respiratory infection (SARI). Herpesviruses were detected in 166 cases
(72.49%), including 85 cases of cytomegalovirus (CMV), 64 cases of Epstein-Barr virus (EBV), 34 cases of human herpes-
virus-7 (HHV-7), 12 cases of human herpesvirus-6 (HHV-6), and 6 cases of herpes simplex virus type 1 (HSV-1). Addition-
ally, 53 cases of torque teno virus (TTV) and 7 cases of torque teno mini virus (TLMV) were detected. CMV prevalence was
highest in neonates, while EBV peaked in the 3–6 year group (37.78%). HSV-1 and HHV-6 were predominantly identied
in severe infections.
Conclusion Herpesviruses, particularly CMV and EBV, were the most frequently detected viruses, followed by anellovi-
ruses. The age-specic viral distribution patterns provide novel epidemiological perspectives for understanding pediatric
respiratory pathogenesis, though their clinical signicance requires validation through mechanistic studies.
Clinical trial number Not applicable.
Keywords Respiratory tract · Virome · Children · Commensal viruses · Metagenomic next-generation sequencing
Received: 16 March 2025 / Accepted: 18 April 2025
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025
Respiratory virome in hospitalized children and analysis of its
correlation with disease severity
JingLiao1,2· Jian HuaWei1,2· JiaoLiu1,2· LuoRen1,2· NaZang1,2· EnmeiLiu1,2
1 3
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
ResearchGate has not been able to resolve any citations for this publication.
Epidemiology, Clinical Significance, and Diagnosis of Respiratory Viruses and Their Co-Infections in the Post-COVID Era
Article
Full-text available
  • Mar 2025
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel human coronavirus, emerged in late 2019 and rapidly evolved into a pandemic around the world. The coronavirus disease (COVID-19) pandemic has dramatically changed the epidemiology and seasonality of other traditional respiratory viruses, e.g., influenza, respiratory syncytial virus, enterovirus, etc. These traditional respiratory viruses have transmission mode and clinical symptoms similar to SARS-CoV-2 but may differ in clinical outcomes and management. Co-infection between SARS-CoV-2 and one or more traditional respiratory viruses have been reported in the literature but have shown mixed evidence in clinical outcomes. With SARS-CoV-2 evolving into mild Omicron variants, it is believed that SARS-CoV-2 co-circulates with other respiratory viruses, which in turn affect the epidemiology and clinical course of respiratory viral infections. In response to these changes, multiplex molecular tests for SARS-CoV-2 and one or more traditional respiratory viruses are attracting more attention in the field and have been developed into a variety of testing modalities. In this review, we describe the seasonality (i.e., in the Northern Hemisphere), epidemiology, and clinical significance of traditional respiratory viruses and their co-infection with SARS-CoV-2 in the post-COVID era. Furthermore, we review commonly used multiplex molecular tests and their applications for the detection of respiratory viruses and their co-infections. Altogether, this review not only sheds light on the epidemiology and clinical significance of respiratory viral infections and co-infections in the post-COVID era, and but also provides insights into the laboratory-based diagnoses of respiratory viral infections using multiplex molecular testing.
View
Assessment of Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV) as Complementary Biomarkers to Torquetenovirus (TTV)
Article
Full-text available
Recent studies have identified Torquetenovirus (TTV) as a promising biomarker of immune competence, particularly in assessing the vaccine response of solid organ transplant (SOT) recipients. However, given the individual variability of viral load, it is not yet possible to define "normal levels”. Nevertheless, TTV is just one component of the broader Anelloviridae family, which also includes Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV). This study explores whether the viremia of TTMV and TTMDV offers a stronger predictive marker for vaccine efficacy in SOT recipients. A cohort of 168 SOT patients (142 kidney and 26 lung transplant recipients) who received the BNT162B2 mRNA vaccine was examined, with viral loads quantified through virus-specific real-time PCR. While TTV remains a potentially useful biomarker for evaluating immune response, the combined analysis of all anelloviruses viremia provides deeper insights, particularly in cases where TTV is undetectable. Notably, only TTMV exhibited a pattern similar to TTV, suggesting its potential as an alternative biomarker when TTV is absent from the patient’s virome.
View
Impact of Point-of-Care Testing on Diagnosis, Treatment, and Surveillance of Vaccine-Preventable Viral Infections
Article
Full-text available
  • Jan 2025
With the advent of a variety of vaccines against viral infections, there are multiple viruses that can be prevented via vaccination. However, breakthrough infections or uncovered strains can still cause vaccine-preventable viral infections (VPVIs). Therefore, timely diagnosis, treatment, and surveillance of these viruses is critical to patient care and public health. Point-of-care (POC) viral diagnostics tools have brought significant improvements in the detection and management of VPVIs. These cutting-edge technologies enable prompt and accurate results, enhancing patient care by facilitating timely treatment decisions. This review delves into the advancements in POC testing, including antigen/antibody detection and molecular assays, while focusing on their impact on the diagnosis, treatment, and surveillance of VPVIs such as mpox, viral hepatitis, influenza, flaviviruses (dengue, Zika, and yellow fever virus), and COVID-19. The role of POC tests in monitoring viral infection is crucial for tracking disease progression and managing outbreaks. Furthermore, the application of POC diagnostics has shown to be vital for public health strategies. In this review, we also highlight emerging POC technologies such as CRISPR-based diagnostics and smartphone-integrated POC devices, which have proven particularly beneficial in resource-limited settings. We underscore the importance of continued research to optimize these diagnostic tools for wider global use for mpox, viral hepatitis, influenza, dengue, and COVID-19, while also addressing current challenges related to their sensitivity, specificity, availability, efficiency, and more.
View
Genetic Conservation and Diversity of SARS-CoV-2 Envelope Gene Across Variants of Concern
Article
Full-text available
  • Jan 2025
  • J MED VIROL
SARS-CoV-2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved and evolving slowly. Pan-sarbecoviruses-conserved regions in the E gene have been used as targets for various RT-PCR assays to detect SARS-CoV-2. It remains elusive whether SARS-CoV-2 variants of concern (VOCs) have accumulated significant E mutations that may affect protein stability and diagnostic RT-PCR assays. Herein we aimed to perform a comprehensive genetic analysis on the conservation and diversity of the E gene of SARS-CoV-2 and its VOCs in comparison with other human coronaviruses (HCoVs). In silico analysis of 20 326 HCoV E gene sequences retrieved from GenBank and GISAID suggests that SARS-CoV-2 E gene has multiple pan-HCoVs-and pan-SARS-CoV-2-conserved positions but accumulates significant mutations in VOC B.1.351 and Omicron strains. Mutations were often found in the 5′ and 3′ variable regions, whereas the central region is conserved. Nucleotide changes C109U and A114G may lead to potential failure of first-line SARS-CoV-2 diagnostic/ screening assays. Nucleotide change C212U and its concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) is a hallmark mutation of B.1.351 variants, while C26U/Thr9Ile is characteristic of all Omicron variants. Later Omicron subvariants, such as XBB.1.5 and EG.5, additionally acquired the A31G/Thr11Ala mutation, as was confirmed by whole genome sequencing of SARS-CoV-2 in 118 pediatric cases. Wild-type E protein exhibits cytotoxicity to cells, but the mutations Thr9Ile, Thr11Ala,
View
Impact of induction agents and maintenance immunosuppression on torque teno virus loads and year-one complications after kidney transplantation
Article
Full-text available
  • Nov 2024
Background Torque teno virus load (TTVL) is gaining importance as a surrogate parameter to assess immunocompetence in kidney transplant recipients. Although the dynamics of TTVL have been investigated before, the impact of different induction agents and variations in immunosuppressive maintenance therapies on TTVL remain unknown. Methods In this retrospective study, TTVL was quantified in 537 plasma or serum samples from 134 patients transplanted between 2018 and 2021. TTVL was examined pre-transplantation and 30-, 90-, 180-, and 360-days post-transplant. To assess the influence of induction therapy on TTVL, 67 patients receiving anti-thymocyte globulin (ATG) induction were matched with 67 patients receiving an interleukin-2 receptor antagonist (IL2-RA) induction in terms of age, sex, and donor modality. Results Following transplantation, there was a steep increase in TTVL post-transplant for all patients with peak viral loads at 90 days post-transplant (median TTVL [IQR] 7.97×10⁶, [4.50×10⁵–1.12×10⁸]) followed by subsequently declining viral loads. Compared to patients receiving IL2-RA as induction therapy, patients receiving ATG had significantly higher peak viral loads 3 months post-transplant (median TTVL [IQR] 2.82×10⁷ [3.93×10⁶–1.30×10⁸] vs. median TTVL [IQR] 2.40×10⁶ [5.73×10⁴–2.60×10⁷]; P<0.001). Throughout all post-transplant time points, patients receiving additional rituximab for induction along with higher tacrolimus target levels exhibited the highest TTVL. Patients whose TTVL 3-months post-transplant exceeded the currently proposed cutoff to predict infections within the first year post-transplant [6.2 log10] showed a trend towards a higher risk of being hospitalized with an infection in the following 9 months, albeit without being statistically significant (HR=1.642, P=0.07). Conclusions Higher TTVL reflects the greater immunosuppressive burden in immunological high-risk patients receiving intensive immunosuppression. The choice of induction agent and intensified immunosuppressive maintenance therapy notably affects TTVL at 3 months post-transplant and beyond, necessitating careful consideration when interpreting and applying TTVL cutoffs to monitor immunocompetence post-transplant.
View
Epidemiological and clinical overview of the 2024 Oropouche virus disease outbreaks, an emerging/ re-emerging neurotropic arboviral disease and global public health threat
Article
Full-text available
  • Sep 2024
In the context of rapid spread of Oropouche virus (OROV), an emerging/re-emerging neutronic arbovirus, from Central/South America to the Caribbean in 2024, this communication represents an alarming message to enhance the awareness of this global public health threat and highlight the importance of heightened vigilance for diagnosis, management, and prevention/control of this disease.
View
The interplay of co-infections in shaping COVID-19 severity: Expanding the scope beyond SARS-CoV-2
Article
Full-text available
  • Jun 2024
High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co-infections by other pathogens and their involvement in the severity of COVID-19. J o u r n a l P r e-p r o o f Interleukin; ILC2, Type 2 innate lymphoid cells; IRAK, Interleukin-1 receptor-associated kinase;
View
Cytomegalovirus Pneumonia in a Patient with Down Syndrome
Article
Full-text available
Down syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and they represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, when causing interstitial pneumonia, associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient with DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation, and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough, and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.
View
Analysis of a Cohort of 165 Pediatric Patients with Human Bocavirus Infection and Comparison between Mono-Infection and Respiratory Co-Infections: A Retrospective Study
Article
Full-text available
  • Jan 2024
Introduction: Human Bocavirus (HBoV) is mainly associated with respiratory tract infections. However, its role as respiratory pathogen is not fully understood for a high co-infection rate in symptomatic patients and a significant HBoV detection rate in asymptomatic subjects. This study aimed to describe a large cohort of children with HBoV infection and to compare HBoV mono-infection and co-infections. Methods: We retrospectively reviewed data from 165 children admitted to Meyer Children’s Hospital IRCCS from March 2022 to March 2023 with the diagnosis of HBoV infection, detected using Reverse Transcription qPCR from nasal swabs. Thereafter, we compared patients with HBoV mono-infection (Group A) and those with HBoV co-infections (Group B) in terms of disease severity, established by the length of stay (LOS), the requirement of Pediatric Intensive Care Unit (PICU), and advanced respiratory support (ARS). Results: The median age was 1.5 years; 80% of patients presented with respiratory symptoms. The discharge rate from the emergency department (ED) within 24 h was 42.4%. Most cases (57.6%) were hospitalized, and 7.3% were admitted to PICU due to respiratory failure. Group A comprised 69 patients, and Group B 96 children (95% viral co-infections, 2% bacterial, 3% viral and bacterial). Group A and Group B were similar in hospitalization rate but differed significantly in LOS (median 3 vs. 5 days) and requirement of PICU admission (0 vs. 12 patients, p < 0.001). Patients with a respiratory disease history (17.5%) showed significantly longer LOS and more necessity of inhaled bronchodilator therapy. Conclusions: HBoV should be considered a relevant respiratory pathogen especially in viral co-infections. Patients with HBoV co-infections have a higher risk of necessitating advanced respiratory support with more PICU admission and longer LOS; a previous respiratory disease puts them at a higher risk of longer hospitalization.
View
SCANellome: Analysis of the Genomic Diversity of Human and Non-Human Primate Anelloviruses from Metagenomics Data
Article
Full-text available
  • Jul 2023
Anelloviruses are extremely prevalent in the human population and are considered to be commensal parts of the human virome. The best-known member in humans is the Torque teno virus. Recent metagenomic next-generation sequencing investigations have helped reveal the considerable number of species and genotypes from the same genus that can be co-detected within a single individual and that this diversity increases as a function of age during the first months/years of life. As a result, to date, the bioinformatics analysis of this genetic diversity remains complex and constraining for researchers. Here, we present SCANellome, a user-friendly tool to investigate the anellome composition at the genus, species, and genotype levels of samples from metagenomics data generated by the Illumina and Nanopore platforms. SCANellome is based on an in-house up-to-date database that includes all human and non-human primate anellovirus reference sequences available on GenBank and meets the latest classification criteria established by the International Committee on Taxonomy of Viruses.
View