A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia

Baillie, Vicky L.; Moore, David P.; Mathunjwa, Azwifarwi; Morailane, Palesa; Simões, Eric A F; Madhi, Shabir A.

doi:10.1016/j.jcv.2020.104288

Cited by 13 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The serum viral load in HAdV-7 infection is notably high, which is consistent with our previous research on severe cases in children [13]. This observation aligns with studies that have shown an increased serum viral load in children infected with other respiratory viruses [11,37]. Not only did we detect a rise in the copy number of the HAdV-7 ber gene in mouse serum (Fig.…”

Section: Discussionsupporting

confidence: 93%

Human adenovirus type 7 (HAdV-7) infection induces damage to pulmonary vascular endothelial cells by activating autophagy in human lung microvascular endothelial cells

Chen,

Yang,

Rao

et al. 2024

Preprint

View full text Add to dashboard Cite

Background HAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous clinical studies have shown a significant increase in serum levels of vascular endothelial growth factor (VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to pulmonary vascular endothelial cells and increased vascular permeability. Further research is necessary to elucidate the underlying mechanism behind this finding. Methods The human lung microvascular endothelial cell line-5a (HULEC-5a) and human CD46 mice (hCD46) were utilized for in vitro and in vivo experiments, respectively. Correlative omics analysis was performed using gene set enrichment analysis (GSEA) and gene ontology (GO) enrichment analysis. Transmission electron microscope (TEM) was employed to observe cellular ultrastructure and virus particles, while immunofluorescence was used to detect the viral protein Hexon to investigate viral infection status. Various methods, including ELISAs for VEGF and other injury markers, qPCR for HAdV-7 fiber gene levels, the CCK8 assay for cell viability, and flow cytometry analysis for endothelial cell numbers, were employed to evaluate endothelial cell damage. Acute lung injury (ALI) severity was evaluated by scoring pathological inflammation and measuring pulmonary vascular permeability. Autophagy activation was assessed by observing autophagosomes and validating marker proteins. Results GSEA analysis revealed significant enrichment in gene sets associated with endothelial functions (barrier, defense, and regeneration) and ALI in the HAdV-7-infected group. GO analysis suggested an enrichment of autophagy-related pathways associated with cell death. Subsequently, successful signs of infection were observed in lung endothelial cells with HAdV-7, including intracellular virions in HULEC-5a cells and perivascular viral protein Hexon in mouse lungs. Lung endothelial cell injury was observed after HAdV-7 infection, showing cytopathic effects, mitochondrial damage, and elevated levels of endothelial injury markers such as sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, and IL1β. Furthermore, a decrease in the number of CD45-CD31+ endothelial cells was noted. Moreover, increased VEGF expression and HAdV-7 fiber gene copy number were detected in the cellular supernatant, mice blood, bronchoalveolar lavage fluid/lung tissue. Additionally, evidence of leaky lung blood vessels and ALI were observed, including progressive weight loss, elevated pulmonary vascular permeability, significant inflammatory cells infiltration, alveolar congestion, structural destruction, and lung consolidation. Furthermore, HAdV-7 infection induced autophagosome formation in endothelial cells and triggered complete cell autophagy. Importantly, inhibiting autophagic flux reduced VEGF levels and other markers of endothelial injury, decreased the copy number of the HAdV-7 fiber gene, improved cell survival rate, reduced pulmonary vessel leakage, and alleviated inflammation in lung tissue. Conclusions HAdV-7 infection induces damage to pulmonary endothelial cells, resulting in elevated VEGF levels, a high viral load, and ALI/ARDS. Activation of endothelial autophagy may be an important mechanism underlying these observations.Targeting autophagy could be a novel approach to rescue pulmonary endothelial cell damage and improve the poor prognosis in severe HAdV-7 infection.

show abstract

Section: Discussionsupporting

confidence: 93%

Human adenovirus type 7 (HAdV-7) infection induces damage to pulmonary vascular endothelial cells by activating autophagy in human lung microvascular endothelial cells

Chen,

Yang,

Rao

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Co-occurrence of bacteria and viruses was common in our study, as measured by either the higher (Ct-value <35) or the lower (Ct-value <30) detection level with rates of 72% and 33%, respectively. A similar rate (76%) of bacterial and viral co-occurrence was reported among the control children from the general population in the PERCH multi-center pneumonia study [ 6 , 29 ]. Variable rates of multiple pathogens have been described in Gambian infants (94%), in healthy Tanzanian children (83%) and in healthy children aged from 6 weeks to 24 months in the Netherlands (38%) [ 32 – 34 ].…”

Section: Discussionsupporting

confidence: 69%

“…Rhinovirus was found to be equally common in pneumonia cases as in control children in the Pneumonia Etiology Research and Child Health (PERCH) multi-center study performed in seven countries in Africa and Asia [ 6 ]. Also, in children from the Soweto township of Johannesburg in South Africa the prevalence of rhinovirus was similar among pneumonia cases and controls (23% versus 22%) with a much lower prevalence in the control group as compared to the findings of our study [ 29 ]. In Russia, rhinovirus was more frequently detected in healthy controls than in children with community-acquired pneumonia; the same was found in Tanzania for control children as compared to those with acute febrile illness[ 7 , 30 ].…”

Section: Discussionsupporting

confidence: 62%

High bacterial and viral load in the upper respiratory tract of children in the Democratic Republic of the Congo

et al. 2020

View full text Add to dashboard Cite

Background Respiratory pathogens including Streptococcus pneumoniae and Haemophilus influenzae , are implicated in the pathogenicity of acute lower respiratory infection (ALRI). These are also commonly found in both healthy and sick children. In this study, we describe the first data on the most frequent bacteria and viruses detected in the nasopharynx of children from the general population in the Eastern DR Congo. Methods From January 2014 to June 2015, nasopharyngeal samples from 375 children aged from 2 to 60 months attending health centres for immunisation or growth monitoring were included in the study. Multiplex real-time PCR assays were used for detection of 15 different viruses and 5 bacterial species and for determination of pneumococcal serotypes/serogroups in the nasopharyngeal secretions. Results High levels of S. pneumonia e were detected in 77% of cases, and H . influenzae in 51%. Rhinovirus and enterovirus were the most commonly found viruses, while respiratory syncytial virus (RSV) was rare (1%). Co-occurrence of both bacteria and viruses at high levels was detected in 33% of the children. The pneumococcal load was higher in those children who lived in a dwelling with an indoor kitchen area with an open fire, i.e. a kitchen with an open fire for cooking located inside the dwelling with the resultant smoke passing to the living room and/or bedrooms; this was also higher in children from rural areas as compared to children from urban areas or children not living in a dwelling with an indoor kitchen area with an open fire/not living in this type of dwelling. Immunization with 2–3 doses of PCV13 was associated with lower rates of pneumococcal detection. Half of the identified serotypes were non-PCV13 serotypes. The most common non-PCV13 serotypes/serogroups were 15BC, 10A, and 12F, while 5, 6, and 19F were the most prevalent PCV13 serotypes/serogroups. Conclusions The burden of respiratory pathogens including S. pneumonia e in Congolese children was high but relatively few children had RSV. Non-PCV13 serotypes/serogroups became predominant soon after PCV13 was introduced in DR Congo.

show abstract

“…Exacerbations of asthma and other pre-existing diseases such as chronic obstructive pulmonary disease and cystic fibrosis in both adults and children has furthermore been associated with lower respiratory infection with RV (Varkey and Varkey 2008, Stelzer-Braid, Liu et al 2017, Zheng, Wang et al 2018, Cafferkey, Coultas et al 2020, Michi, Love et al 2020, Ortega, Nickle et al 2020, Zhu, Mallia et al 2020. There is also increasing evidence to suggest RV-A and RV-C species may be associated with more severe disease compared to RV-B strains (Lee, Lemanske Jr et al 2012, Megremis, Niespodziana et al 2018, Ng, Oong et al 2018, Baillie, Moore et al 2020, and similar efforts have been made to examine the varied clinical manifestations between RV subtypes (Huang, Wang et al 2009, Moreira, Kamikawa et al 2011, Bruning, Thomas et al 2015, Martin, Kuypers et al 2015, Bergroth, Aakula et al 2020. In order to better understand potential associations between RV species and clinical features among paediatric cases, we aimed to integrate genetic and epidemiological data using Bayesian phylogenetic methods.…”

Section: Introductionmentioning

confidence: 99%

The Molecular Epidemiology and Clinical Phylogenetics of Rhinoviruses Among Paediatric Cases in Sydney, Australia

Adam

Chen

Scotch

et al. 2021

International Journal of Infectious Diseases

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia

Cited by 13 publications

References 28 publications

Human adenovirus type 7 (HAdV-7) infection induces damage to pulmonary vascular endothelial cells by activating autophagy in human lung microvascular endothelial cells

Human adenovirus type 7 (HAdV-7) infection induces damage to pulmonary vascular endothelial cells by activating autophagy in human lung microvascular endothelial cells

High bacterial and viral load in the upper respiratory tract of children in the Democratic Republic of the Congo

The Molecular Epidemiology and Clinical Phylogenetics of Rhinoviruses Among Paediatric Cases in Sydney, Australia

Contact Info

Product

Resources

About