Search Results (65)

Background: Human rhinoviruses (HRVs) exhibit a global circulation characterized by prolonged epidemics and a less concentrated seasonal distribution compared with other respiratory viruses. In this study, we describe the timing, amplitude and duration of HRV epidemics on a global scale, analyzing seasonal patterns in relation to geographic latitude. Methods: HRV surveillance data reported to WHO FluNet from 2016 to 2025 were analyzed. Epidemic peak timing, amplitude and duration were estimated as a function of geographic latitude using harmonic analyses, with a comparison between the pre-pandemic (2016–2019) and post-pandemic (2021–2025) periods. Results: During the study period, 432,399 HRV detections were reported to WHO FluNet across 50 countries. Among these, 24 countries met the predefined criteria for seasonal analysis. Epidemic peak timing showed differences consistent with latitude, with peaks occurring in late autumn and winter in the Northern Hemisphere, during the central months of the year in the Southern Hemisphere, and greater temporal variability in the intertropical belt. Peak amplitude showed marked heterogeneity across countries (median 68.2%, range 28.1–96.7%), while epidemic duration indicated prolonged circulation (median 31 weeks, range 5–48 weeks). A secondary seasonal peak was identifiable in most countries, further supporting the relatively diffuse seasonal profile of HRV circulation. Comparison between the pre- and post-pandemic periods showed largely stable peak timing in most countries, alongside heterogeneous changes in peak amplitude. Conclusions: HRV is characterized by prolonged and weakly concentrated seasonal activity, with epidemic circulation often extending over several months. Despite major epidemiological perturbations during the COVID-19 pandemic, the timing of seasonal peaks remained largely stable across countries, highlighting the epidemiological resilience of HRV and the need for continuous, pathogen-specific surveillance. Full article

Human rhinoviruses (HRVs) are the primary cause of the common cold, a highly contagious upper respiratory tract infection characterized by nasal congestion, sneezing, and sore throat. HRV replication depends on its 3C protease (HRV-3Cpro), a key enzyme that cleaves the viral polyprotein into functional proteins essential for viral maturation. Currently, no FDA-approved inhibitors specifically target HRV-3Cpro. While rupintrivir, a synthetic inhibitor, advanced to clinical trials, it ultimately failed due to limited efficacy. This study investigated the potential of Vitex negundo (or lagundi)—a medicinal plant traditionally used in the Philippines for treating colds and respiratory ailments—as a source of natural HRV-3Cpro inhibitors through in silico molecular docking and pharmacokinetic (ADMET) evaluation. Fifteen phytochemicals were screened, with five compounds exhibiting strong binding affinities exceeding that of the reference inhibitor rupintrivir (−6.1 kcal/mol): agnuside (−6.9 kcal/mol), luteolin 7-O-glucoside (−6.7 kcal/mol), 2′-p-hydroxybenzoyl mussaenosidic acid (−6.5 kcal/mol), 6′-(p-hydroxybenzoyl) mussaenosidic acid (−6.5 kcal/mol), and luteolin (−6.2 kcal/mol). Among these, luteolin emerged as a particularly promising lead compound, forming stable hydrogen bonding and hydrophobic interactions with HRV-3Cpro. Luteolin also demonstrates a favorable ADMET and safety profile, predicted to be non-mutagenic and non-hepatotoxic. These findings position luteolin as a potential plant-based HRV-3Cpro inhibitor, warranting further in vitro and in vivo studies to validate its antiviral efficacy and pharmacokinetic properties. Full article

Acute respiratory infections (ARIs) remain a common cause of morbidity and mortality in children, especially in sub-Saharan Africa, where countries such as Ghana are severely affected. This review presents recent data on ARI etiology, clinical burden, and antimicrobial resistance (AMR) from Ghana, spanning the pre-COVID-19 era (2010–2019) to the post-pandemic period (2020–2025). Before the COVID-19 pandemic, viral infections, such as respiratory syncytial virus (RSV), rhinoviruses, and influenza viruses, were the major contributors, along with established bacterial pathogens such as Streptococcus pneumoniae and Haemophilus influenzae. Social determinants, including undernutrition and indoor air pollution, also influenced these infections. In the COVID era, we have seen dramatic shifts in pathogen seasonality, the scaling of oxygen delivery systems, and the implementation of genomic surveillance for SARS-CoV-2, as well as new features such as maternal RSV vaccination and monoclonal antibody therapy. Despite its successes in vaccination coverage and health system strengthening, some challenges remain, including fluctuations in implementation and surveillance issues. The simultaneous challenges of pneumonia and hygiene will require integrated, coordinated, multisectoral responses that incorporate surveillance with antibiotic stewardship, sustainable oxygen systems, and interventions for nutrition and environmental health. The review also highlights research priorities and makes policy recommendations well aligned to support national ARI control efforts aimed at reducing child mortality due to ARI and achieving Sustainable Development Goals targets on child health. Full article

Background: Rhinovirus C (RV-C) is one of three species of rhinoviruses (RVs), which cause the common cold, preschool wheezing illnesses and exacerbations of asthma. RV-C types are more virulent, especially in children, but progress in developing treatments is limited by difficulties in generating high-titer virus preparations. The goals of this study were to optimize methods for large-scale production and purification of RV-C to facilitate structure and immune response studies. Methods: We optimized protocols for the propagation and purification of RV-C15a, a clinical isolate adapted to HeLa-E8 cells stably expressing virus receptor CDHR3. We compared virus yields in adherent and suspension cultures, evaluated the effects of calcium supplementation and infection timing, and tested multiple purification strategies, including ultracentrifugation, dialysis, and lipase treatment. Results: RV-C15a yields were significantly lower in suspension vs. adherent cultures despite comparable virus binding and entry, suggesting post-entry replication limitations in suspended cells. In adherent cultures, infecting soon after cell seeding and calcium supplementation reduced the time of virus production and modestly improved virus progeny yields. Surface CDHR3 expression declined over time, potentially restricting viral spread. Among purification methods, lipase treatment of infected cell lysates followed by ultracentrifugation produced highly pure and concentrated virus preparations suitable for structural and immunological applications, with high yields. Conclusions: We present a robust system for large-scale RV-C15a production in adherent HeLa-E8 cells and recommend a lipase-based purification method as a rapid and effective approach for producing high-quality viral preparations. These advances will support structural studies and accelerate the development of RV-C-targeted therapeutics and vaccines. Full article

Respiratory viruses such as SARS-CoV-2, influenzas A and B, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human parainfluenza virus type 3 (HPIV-3), and rhinoviruses remain major causes of global morbidity. Their rapid evolution, high transmissibility, and limited therapeutic options, together with the absence of approved vaccines for several pathogens, highlight the need for broad-acting and pathogen-independent antiviral strategies. Nitric oxide exhibits antiviral activity through redox-dependent mechanisms, including S-nitrosylation of cysteine-containing viral proteins and disruption of redox-sensitive structural domains. Clinical studies conducted during the SARS-CoV-2 pandemic demonstrated that a nitric oxide nasal spray (NONS) rapidly reduced nasal viral load and transmission. In this study, we evaluated the in vitro virucidal activity of the NONS against a panel of clinically relevant respiratory viruses representing four major virus families. Virus suspensions of approximately 10⁴ CCID₅₀ were exposed to a full-strength NONS for contact times ranging from 5 s to 2 min at room temperature, followed by neutralization and quantification of residual infectivity using endpoint dilution assays. The NONS rapidly reduced viral infectivity across all viruses tested, achieving >3 log₁₀ reductions within 2 min. SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, Omicron BA.1, and XBB 2.0 were reduced to levels at or below the assay detection limit within 30 s to 2 min. Influenza A and B viruses showed the fastest loss of infectivity, reaching detection limits within 10–15 s. RSV, hMPV, HPIV-3, and human rhinovirus 14 were similarly inactivated within 1–2 min. These findings demonstrate that the NONS exhibits rapid and broad-spectrum virucidal activity against diverse respiratory viruses and supports its potential role in pandemic preparedness but also seasonal use. Full article

This review highlights the role of temperature sensitivity, a common feature of attenuated virus vaccines, in mediating attenuation. Viral attenuation mechanisms were analyzed by comparing vaccine characteristics and genes with those of wild-type viruses. Development of varicella vaccines, particularly their attenuation and immunogenicity in immunocompromised children, provided key insights into these mechanisms. Temperature sensitivity leads to smaller viral microlesion formation than wild-type virus by impaired viral replication before recognition by the innate immune system, eliciting protective immunity without causing clinical symptoms. Vaccine candidates were selected based on their attenuation in humans and replication ability for mass production, with impaired growth and temperature sensitivity as common characteristics among many vaccines. Temperature-sensitive rhinoviruses replicate in the nasal mucosa at 33 °C but not in the lungs at 37 °C, demonstrating in vitro and in vivo temperature sensitivity. Similarly, vaccine-induced immunity arises from viral microlesions caused by impaired growth of temperature-sensitive strains; however, these lesions remain small and result in attenuated clinical symptoms. Because of this impaired growth, higher inoculation doses than those of wild-type strains are required to establish infection and elicit immunity. Therefore, clinical attenuation results from impaired viral replication due to temperature sensitivity, yet it induces protective immune responses. Full article

The Indo-Pacific region hosts several annual military exercises that involve the deployment of thousands of U.S. and partner-nation military personnel. Respiratory and diarrheal diseases pose a significant health risk to exercise participants and represent a substantial portion of medical encounters and lost duty days. We conducted surveillance for respiratory and diarrheal illness at the Cobra Gold and Balikatan military exercises in Thailand and the Philippines from 2023–2025. Through coordination with health providers in the field, military personnel that reported acute symptoms were asked to provide a nasopharyngeal swab or stool sample. These samples were transported to a field lab and tested by PCR for common respiratory and diarrheal pathogens. Follow-up analyses included bacterial culture, antimicrobial susceptibility testing, and viral whole-genome sequencing. From 84 respiratory and 61 diarrheal samples analyzed, we found that respiratory illness was primarily attributed to rhinoviruses/enteroviruses (23%), common coronaviruses (21%), and SARS-CoV-2 (11%) while diarrheal disease was attributed to a high rate of diarrheagenic E. coli (73%) and norovirus (20%), followed by Salmonella spp. (18%) and Campylobacter spp. (13%). Our findings highlight the distinct etiologies of respiratory and diarrheal disease in military field settings and demonstrate the feasibility of conducting real-time infectious disease surveillance in operational environments. Full article

Background: While rhinoviruses (RVs) typically cause mild respiratory infections, their persistence during the SARS-CoV-2 pandemic, particularly in Hong Kong’s strict zero-coronavirus disease 2019 policy, revealed unexpected epidemiological patterns. Two distinct RV surges emerged despite stringent public health measures, suggesting unique transmission advantages among circulating strains. We hypothesised that RV persistence during pandemic restrictions reflected strain-specific adaptations in respiratory tract replication efficiency and/or immune evasion. Methods: We analysed RV genotypes and conducted blinded clinical severity assessment for 96 paediatric hospitalisations during 2020–2021 outbreaks, compared with 180 age- and sex-matched control subjects from the corresponding weeks in pre-pandemic years (2018–2019). RV isolates from 2020 to 2021 outbreaks were characterised for their replication competence and transcriptomic responses in primary human nasal epithelial cell (HNEC) and environmental stability assays, using RV-A16 and RV-A1B as controls. Result: Minor group genotypes RV-A47 and RV-A49 were overrepresented during these two outbreaks. RV-A49 exhibited comparable replication efficiency to RV-A16 but induced significantly stronger transcriptomic responses, notably enhanced TNF and IL-1 signalling, in HNECs, alongside robust replication competence. Our data also suggests the association of RV-A49 with tachypnoea in 2021, particularly in younger males, though limited by a small sample size and single-centre design. Conclusion: The predominance of RV-A49 in hospitalised children during the SARS-CoV-2 pandemic potentially driven by its replication competence in HNECs and its capacity to enhanced inflammatory responses. The result is hypothesis-generating, warranting further studies with historical strains and broader populations to confirm strain-specific severity. Full article

Background/Objectives: Enterovirus-D68 (EV-D68) and rhinoviruses are major contributors to respiratory illnesses in children, presenting a spectrum of clinical manifestations ranging from asymptomatic cases to severe lower respiratory tract infections. No specific antiviral treatments are currently approved for these viruses. Method: We conducted a comprehensive literature review of antiviral agents investigated for EV-D68 and rhinovirus infections. Results: Several antiviral candidates are under investigation, each targeting distinct stages of the viral replicative cycle. Capsid-binding agents and monoclonal antibodies prevent viral attachment by blocking receptor-virus interactions. Inhibitors of viral replication proteins disrupt polyprotein processing and replication organelle biogenesis by targeting non-structural viral proteins. Host factor inhibitors impair viral attachment, replication organelle formation, or RNA replication by interfering with critical host pathways. Conclusions: While no specific antivirals are yet approved for EV-D68 and rhinovirus infections, emerging therapeutic candidates offer potential avenues for treatment. Continued preclinical and clinical investigation will be essential to validate these approaches and expand the available options for affected patients. Full article

Hospital-acquired infections (HAIs) previously focused mainly on multidrug-resistant (MDR) bacteria, with less attention on viruses. The COVID-19 pandemic highlighted the importance of controlling viral infections. Human rhinoviruses (HRVs) are among the viruses responsible for HAIs. HRVs are non-enveloped viruses that infect the upper airways after airborne or direct transmission. Due to their lack of a membrane envelope, HRVs exhibit moderate resistance to commonly applied alcoholic disinfectants. Therefore, there is a significant need to develop alternative disinfection and hand sanitation strategies to control HRV infections in healthcare settings without posing a risk to human health. The antimicrobial activity and safety of rhamnolipids and rhamnolipids nano-micelles (RMN) against MDR-bacteria and several viruses, including SARS-CoV-2, were confirmed recently. Also, we previously demonstrated the superior antimicrobial activity of RMN over rhamnolipids. In the current study, molecular docking demonstrated the weak interactions of rhamnolipids with HRV-1A (minor group) compared to HRV-14 (major group), suggesting a superior antiviral activity of rhamnolipids towards major group rhinoviruses. To biologically validate these data, RMN was prepared and characterized, and then antiviral activity against HRV-16 (major group) and HRV-1B (minor group) infection of HeLa cells was assessed. RMN showed a complete inhibition of HRV-16 infection with recovery of 100% of HeLa cell viability. In contrast, only partial inhibition of HRV-1B infection with approximately 50% protection against infection was observed. Therefore, RMN might be recommended as a disinfectant and/or a hand sanitizer component to control the spread of RVs in hospital care settings or elsewhere to reduce the incidence of respiratory infections. Full article

Background/Objectives: Pertussis remains a significant cause of respiratory illness in children, particularly in regions with suboptimal vaccination coverage. This retrospective study analyzes the clinical presentations, co-infections, treatment, and outcomes of pediatric patients diagnosed with Bordetella pertussis at the Constanța County Clinical Emergency Hospital “St. Apostle Andrew” between 1 January and 30 September 2024. Methods: Thirty-eight children, predominantly under the age of 3 years (81.58%), were included. Demographic data, clinical features, coinfecting pathogens, antimicrobial regimens, and hospital outcomes were reviewed. Results: Only 7 out of 38 children (18.42%) had received pertussis vaccination, and none benefited from maternal immunization. The highest incidence occurred in infants under 1 year (44.74%). Intensive care was required in 18.42% of cases, and macrolides were the most frequently used antibiotics (68.42%). Co-detection of respiratory pathogens—particularly Streptococcus pneumoniae, enteroviruses, and human rhinoviruses—was common. Severe cases often exhibited hyperleukocytosis, which was associated with complications such as heart failure. Conclusions: These findings underscore the need for timely recognition and management of pertussis and its complications. Although macrolides remain the first-line therapy, adjunctive treatments like leukoreduction may be considered in critical cases. The persistence of pertussis despite vaccination efforts highlights the challenges posed by waning immunity and diagnostic limitations, reinforcing the need for strengthened public health strategies. Full article

Influenza poses a serious threat to both individual and public health. This study aimed to investigate the virological and epidemiological characteristics of influenza infections and to explore the genetic diversity of the circulating influenza viruses. In total, 1886 nasopharyngeal specimens from patients with acute respiratory illnesses were tested against 13 respiratory viruses using a multiplex real-time PCR. Whole-genome sequencing, phylogenetic, and amino acid analyses of representative influenza strains were performed. At least one respiratory virus was detected in 869 (46.1%) patients; 87 (4.6%) were co-infected with two or three viruses. Influenza A(H1N1)pdm09 was the most prevalent virus (16.1%), followed by rhinoviruses (8.1%) and RSV (6.7%). Hemagglutinin (HA) genes of the 74 influenza A(H1N1)pdm09 viruses were categorized in subclades C.1.8, C.1.9, and C.1 within clade 5a.2a and D1, D.2, and D.3 within clade 5a.2a.1. The A(H3N2) viruses analyzed belonged to clade 2a.3a.1, subclades J.2 and J.1. The sequenced B/Victoria lineage viruses fell into clade V1A.3a.2, subclades C.5.6 and C.5.7. Amino acid substitutions in most viral proteins were identified compared with the vaccine strains, including in the HA antigenic sites. This study demonstrated the dominant distribution of the influenza A(H1N1)pdm09 virus among the respiratory viruses studied and the genetic diversity of the circulating influenza viruses. Full article

In an epidemiologic investigation of Enterovirus (EV) infections in a Verona hospital, September 2022–September 2024, we detected EV-C105 in six pediatric patients with upper respiratory symptoms between March and May 2023. The primary objective was to describe the local incidence of EV cases. The secondary objective was to perform Sanger’s genomic characterization and the whole-genome sequencing (WGS) of EV-C105. The proportion of positive EV results was calculated based on routine molecular method testing. An available cohort of 114 underwent Sanger sequencing, and the six EV-C105 were characterized with WGS. Overall, 96% EV results were from the upper respiratory tract. The total proportion of positives in children was 83%. Out of the typed 114, 90% were Rhinoviruses and 9%, EVs. Notably, six pediatric cases were EV-C105, placing together in a unique cluster with 99% of nucleotides belonging to the European lineage with the highest Average Nucleotide Identity, including EV-C104, EV-C109, and EV-C118. Our data describes the first cluster indicating that EV-C105 incidence may be higher than previously estimated. However, a limitation for affirming this hypothesis is the lack of a more in-depth epidemiological investigation on a larger case series with the possibility of including data from coordinated laboratories. Full article

Respiratory viral infections present significant global health challenges, causing substantial morbidity and mortality, particularly among highly susceptible components of the population. The emergence of pandemics and epidemics, such as those caused by influenza viruses and coronaviruses, emphasizes the urgent need for effective antiviral therapeutics. In this review, we explore the potential of broad-spectrum antiviral agents targeting respiratory RNA viruses, including influenza viruses, coronaviruses, respiratory syncytial virus, human metapneumovirus, human parainfluenza viruses, and rhinoviruses. Various broad-spectrum direct-acting and host-targeting antivirals are discussed, including monoclonal antibodies targeting conserved regions of viral surface proteins, molecules interfering with host cell receptors or viral replication machinery, viral protease inhibitors, siRNA therapies, ribonuclease, and 3D8 scFv. Advancements in host-targeting approaches to reduce resistance and RNA-based therapeutics offer significant potential for combating respiratory viral threats. Despite challenges, broad-spectrum antiviral agents represent a crucial strategy, particularly when specific viral pathogens are unidentified or rapid intervention is essential, such as during pandemics or outbreaks. Full article

Rhinoviruses and respiratory enteroviruses remain among the leading causes of acute respiratory infections, particularly in children. Little is known about the genetic diversity of enteroviruses and rhinoviruses in pediatric patients with acute respiratory infections in Russia. We assessed the prevalence of human rhinoviruses/enteroviruses (HRV/EV) in 1992 children aged 0 to 17 years hospitalized with acute respiratory infections during the 2023–2024 epidemic season using PCR. The detection rate of HRV/EV was 11% (220/1992). We performed typing of 58 HRV and 28 EV viruses by partial sequencing of the VP1 gene. Rhinovirus A was the most common among HRV, followed by rhinovirus C; rhinovirus B was detected in only three cases. Enteroviruses were represented by all four species, with the EV-D68 genotype being the most frequently detected. Phylogenetic analysis of the VP1 fragment of EV-D68 showed that all our sequences belonged to the B3 subclade. We identified the first case of EV-C105 infection in Russia in a two-year-old girl hospitalized with pneumonia. Phylogenetically, the Novosibirsk strain EV-C105 was closely related to a strain discovered in France in 2018. This research helped to fill a critical gap in understanding the epidemiological landscape of HRV/EV in pediatric populations within Russia. Full article