Lili Xu

Human adenovirus type 7 (HAdV-7) is a significant pathogen responsible for viral community-acquired pneumonia in children. To date, no specific antiviral agents have been approved for clinical use against HAdV infections. Traditional Chinese medicine (TCM) mixtures have shown promising potential in managing viral pneumonia. This study aimed to evaluate the antiviral activity of Yuanzhixingrenheji (YZ), a hospital-prepared TCM formulation from Beijing Children’s Hospital, against HAdV-7. Initial screening of four hospital formulations (Feiyanheji, Qingjieheji, Yindaizhikeheji, and Yuanzhixingrenheji) using a CCK-8 assay revealed that YZ exhibited the lowest cytotoxicity. In vitro, YZ pretreatment and post-infection treatment exhibited dose-dependent antiviral activity against HAdV-7 in A549 cells, significantly suppressing the DBP mRNA level and protein expression while reducing viral genome copies, HAdV-7-GFP fluorescence, hexon fluorescence, and DBP nuclear localization. In the hDSG2^+/+ C57BL/6 mouse model of HAdV-7 infection, YZ effectively mitigated infection-induced body weight loss and substantially reduced viral loads in lung tissue. Furthermore, a clinical retrospective analysis indicated that YZ treatment significantly decreased post-hospitalization serum C-reactive protein levels of pediatric patients with HAdV infection in various disease severities. Compared with conventional treatment, YZ treatment also significantly reduced peak temperature and shortened the duration of fever in children with HAdV infection, supporting its therapeutic potential. In summary, this study provides the first integrated evidence from in vitro, in vivo, and clinical retrospective investigations, demonstrating that the TCM mixture YZ has significant anti-HAdV-7 activity and clinical efficacy. Characterized by a favorable safety profile and low economic burden, YZ is a promising candidate for the treatment of pediatric adenovirus pneumonia.

Scrub typhus, a zoonosis caused by Orientia tsutsugamushi ( O. tsutsugamushi ), remains a significant public health threat in the Asia-Pacific region. This disease is transmitted through the bite of infected trombiculid mite larvae (chiggers) and typically manifests as acute undifferentiated fever during the early stage. Despite the availability of targeted antibiotic therapies, delayed diagnosis frequently leads to severe complications and fatal outcomes. Here, we report a severe imported paediatric case in Beijing, a city in China's temperate zone, involving a 12-year-old girl with a recent travel history to Yunnan Province. The patient presented with fever, characteristic eschar, regional lymphadenopathy, and septic shock, ultimately progressing to multiorgan dysfunction syndrome. Whole-genome metagenomic next-generation sequencing (mNGS) of blood, cerebrospinal fluid (CSF), and sputum samples revealed O. tsutsugamushi with high sequence read counts, whereas blood cultures remained negative for other bacterial pathogens. Subsequent PCR amplification and Sanger sequencing confirmed the mNGS findings. Phylogenetic analysis of the TSA56 gene classified the strain within the Karp cluster. Serological analysis revealed the presence of O. tsutsugamushi -specific IgM and IgG antibodies. This severe paediatric case highlights the importance of considering travel-associated scrub typhus in the differential diagnosis of febrile illnesses in non-endemic regions. This is particularly relevant for patients with a history of insect bites in areas known to be endemic for O. tsutsugamushi .

Human metapneumovirus (hMPV) is a prevalent respiratory virus in children with acute lower respiratory tract infections that is highly homologous with respiratory syncytial virus (RSV), the primary etiological agent of pediatric upper and lower respiratory tract infections. Although hMPV and RSV are the only human pathogens within the Pneumoviridae family and share similar clinical manifestations, the mechanisms underlying their divergent pathogenicity remain poorly understood. In this study, we performed transcriptomic analysis on clinical respiratory samples collected between 2017 and 2019 from 61 children: including hMPV-infected, RSV-infected and healthy controls. This analysis revealed a shared upregulation of antiviral response pathways, including neutrophil activation and signaling mediated by interferons and interleukins. Conversely, cilium organization and assembly pathways were commonly downregulated in both infections. hMPV infection uniquely upregulated pathways associated with extracellular component activity, ion channel complexes, and neuroactive ligand‒receptor interactions. In contrast, pathways related to membrane rafts and membrane microdomains were uniquely downregulated in hMPV-infected patients. Analysis of differentially expressed immune-related and interferon-stimulated genes revealed significant hMPV-specific increases in EGF and FCGR1A, alongside decreased EPAS1 expression. The genes that were uniquely upregulated during hMPV infection were enriched in cytokine production regulation, cytokine‒cytokine receptor interactions, and PI3K/AKT signaling, whereas those that were uniquely downregulated involved the viral entry and endocytic vesicle pathways. Both hMPV infection and RSV infection significantly increased the proportions of M1 macrophages and neutrophils but decreased the proportions of M0 and M2 macrophages. Notably, hMPV infection resulted in a significant increase in monocytes and activated NK cells coupled with a decrease in resting memory CD4⁺ T cells, compared with RSV infection. The results also revealed a significantly greater relative abundance of Prevotella salivae in the hMPV infection group, whereas Streptococcus salivarius and Streptococcus mitis were enriched in the RSV group. These distinct immune and microbial signatures provide novel insights into the pathogenesis of pediatric hMPV and RSV infections.

Respiratory viruses impose a substantial health burden worldwide, with viral internalization into host cells being the initial step for infection establishment. This process is tightly regulated by the host cellular machinery through two major pathways: receptor-mediated endocytosis and direct membrane fusion. To clarify the role of host factors in these steps, we present human adenovirus and respiratory syncytial virus as representative non-enveloped and enveloped viruses, respectively, as models to elucidate their life cycles, focusing on how host factors mediate their distinct internalization processes. We further categorized the host factors involved in the internalization of other common respiratory viruses, including coronaviruses, influenza A virus, and human metapneumovirus. By analyzing the virus–host interaction mechanisms underlying these processes, this review provides critical insights for developing broad-spectrum antiviral therapies targeting conserved host factors that govern viral internalization.

Human bocavirus (HBoV) is an emerging pathogen associated with pediatric respiratory and gastrointestinal infections, yet its genetic diversity remains understudied. The aberrant global resurgence of other respiratory viruses after the COVID-19 pandemic has raised concerns regarding significant evolutionary shifts in viral genetic profiles. Accordingly, this study characterized HBoV isolates that circulated in Beijing during 2023 by analyzing 1,442 pediatric respiratory samples associated with acute respiratory tract infections. Among 43 HBoV-positive cases with a 2.98% detection rate, 11 complete genomes were sequenced and classified as HBoV1 through phylogenetic analysis. Amino acid substitutions in VP1, including the prevalent N474S mutation (95.3% frequency in GenBank), were predicted via structural modeling to alter hydrogen-bonding networks, potentially enhancing viral stability. Entropy analysis confirmed the high variability of VP1, whereas selective pressure analysis revealed conserved sites under purifying selection in the NP1 and VP1 proteins. Notably, the S79N substitution in NP1 introduced a putatively N-glycosylation site while a putatively O-glycosylation site was lost in four isolates, may suggesting functional implications. No recombination events were detected. These findings provide critical insights into the molecular evolution of HBoV1 and inform future research on antiviral strategies.

Human metapneumovirus (hMPV) is a significant global pathogen that causes acute respiratory tract infections, especially in infants, young children, the elderly, and immunocompromised individuals. Despite its increasing prevalence, there are currently no vaccines or effective treatments available for hMPV. The pathogenesis of hMPV infection is a complex process involving a multitude of host factors and viral receptors. These interactions determine the virus ability to enter host cells, replicate, and evade the immune response. This review is the first to provide a comprehensive overview of the current understanding of host–virus interactions in hMPV pathogenesis. By elucidating these mechanisms, we can identify potential targets for antiviral drugs and improve the management of hMPV infections.

Respiratory syncytial virus (RSV) is one of the most common viruses leading to lower respiratory tract infections (LRTIs) in children and elderly individuals worldwide. Although significant progress in the prevention and treatment of RSV infection was made in 2023, with two anti-RSV vaccines and one monoclonal antibody approved by the FDA, there is still a lack of postinfection therapeutic drugs in clinical practice, especially for the pediatric population. In recent years, with an increasing understanding of the pathogenic mechanisms of RSV, drugs and drug candidates, have shown great potential for clinical application. In this review, we categorize and discuss promising anti-RSV drug candidates that have been in preclinical or clinical development over the last five years.

Background: Human rhinoviruses (HRVs) are among the most common pathogens of upper respiratory infections, and they are responsible for the common cold. An increasing number of studies have shown that HRV is associated with more severe illness. However, HRV-associated fulminant myocarditis has rarely been reported.Patient presentation: A previously healthy 8-year-old boy developed fever, fatigue, and vomiting for 3 days, with a subsequent exacerbation accompanied by confusion lasting for 9 h. The day before admission, the patient presented with oliguria, confusion, and hypotension, and he was suspected of having myocarditis. The patient was transferred to our hospital for further diagnosis and treatment. On admission, rough and moist rales were detected, and the heart sounds were muffled, accompanied by an irregular heart rhythm and a gallop. An electrocardiogram (EKG) revealed a wide QRS complex, ST-segment depression, premature ventricular contractions, and complete right bundle branch block. Laboratory tests revealed that brain natriuretic peptide (BNP), N-terminal pro BNP (NT-pro BNP), and cardiac biomarkers, such as troponin I, creatinine kinase (CK), and creatinine kinase-MB (CK-MB) were elevated. Additionally, echocardiography revealed an ejection fraction of approximately 28%. The child developed severe cardiac dysfunction and tissue hypoperfusion, and the cardiogenic shock could not be corrected despite active drug therapy. He had indications for ECMO implantation. A rarely reported rhinovirus, namely, A66, was detected in his bronchoalveolar lavage fluid and oropharyngeal swabs via metagenomic next-generation sequencing and a PCR assay. Bacterial culture of all the samples yielded negative results.Conclusions: This case presents a patient with severe human rhinovirus A66 infection, which is likely responsible for fulminant myocarditis. This report facilitates prompt diagnosis and treatment of fulminant myocarditis. Clinicians should consider rhinovirus as a possible pathogen of fulminant myocarditis, especially when patients present with symptoms or signs of heart involvement.

Human adenoviruses (HAdVs) are important pathogens responsible for respiratory infections. In children and immunocompromised patients, respiratory infections can cause considerable morbidity and mortality. Currently, there are no approved effective and safe antiviral therapeutics for the clinical treatment of HAdV infections, even those that have undergone preclinical/clinical trials. However, many compounds and molecules with anti-HAdV activity have been explored, and some candidates are undergoing clinical development. Here, we reviewed the reported in vitro and in vivo efficacies, as well as the therapeutic potential of these antiviral compounds, providing an overview and a summary of the current status of anti-HAdV drug development.

The common human coronaviruses (HCoVs) HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 which are members of the coronavirus family are long co-existed with humans and widely distributed globally. Common HCoVs usually cause mild, self-limited upper respiratory tract infections (URTI), and also associated with lower respiratory tract infections (LRTI), especially in children. However, there are little multicentre studies have been conducted in children of several different areas in China, and the epidemic potential of common HCoVs remains unclear. Understanding of the common HCoVs is valuable for clinical and public health. Herein, we retrospectively analysed the medical records of children with acute lower respiratory tract infection admitted to 9 hospitals from different regions in China from 2014 to 2019. Of the 124 patients who tested positive for coronaviruses, OC43 was the predominant type, accounting for 36.3% (45/124) of the detections. Children aged ≤ 6 months and 12–23 months had the highest detection rate of common HCoVs, and the detection rate gradually declined after 2 years old. These four HCoVs could be detected all year round. Among the areas of our study, the overall positive rate was higher in southern China, especially in Guangzhou (29/124, 23.4%). Moreover, common HCoV-positive patients were codetected with 9 other common respiratory pathogens. 229E (11/13, 84.6%) was the most frequently associated with codetection, with EV/RhV was the most frequently codetected virus. Cough (113/124, 91.1%) and fever (73/124, 58.9%) were the most common symptoms of common HCoVs infection.