Search Results (29)

Respiratory pathogens are significant causes of morbidity and mortality worldwide. Since the emergence of SARS-CoV-2 in 2019 and the mitigation measures implemented to control the pandemic, other respiratory viruses’ transmission and circulation patterns were substantially disrupted. We leveraged the influenza hospitalization surveillance in Tanzania to understand the distribution of respiratory viruses shortly after nonpharmaceutical interventions (NPIs) were lifted. A total of 475 samples that tested negative for SARS-CoV-2 and influenza from March through May 2022 were included in this study. The samples were tested for 16 virus targets using Anyplex II RV16 multiplex assays. The findings indicate that most hospitalizations (74%) were among children under 15 years, with human bocavirus (HBoV) being the most prevalent (26.8%), followed by rhinovirus (RV, 12.3%), parainfluenza viruses (PIVs1–4, 10.2%), respiratory syncytial virus (RSV, 8.7%), adenovirus (AdV, 4.3%), and metapneumovirus (MPV, 2.9%). Notably, 54% of respiratory hospitalizations had no viruses detected. The findings highlight the broad circulation of respiratory viruses shortly after NPIs were lifted in Tanzania. Surveillance for respiratory pathogens beyond influenza and SARS-CoV-2 can inform public health officials of emerging threats in the country and should be considered an important pandemic preparedness measure at a global level. Full article

Natural killer (NK) cell adoptive immunotherapy is a promising therapeutic approach in which NK cells perform targeted lysis of tumor cells. Oncolytic viruses are also effective cancer therapeutic agents due to their ability to selectively target and kill tumor cells. Combination therapies that integrate NK cells and oncolytic viruses have been shown to enhance tumor killing compared to individual treatment strategies alone. Using in vitro expanded human NK cells (PM21-NK cells), we tested the relative ability of tumor cells infected with WT parainfluenza virus 5 (PIV5), which is a poor inducer of type 1 interferon (IFN-I), versus PIV5 P/V gene mutant, which is a strong inducer of IFN-I synthesis, to modulate NK cell activities. Both WT and P/V mutant viruses were capable of infecting PM21-NK cells and caused extensive cytopathic effects. Co-culturing of PM21-NK cells with virus-infected tumor cells resulted in spread of WT PIV5 to naïve NK cells, but NK cells were protected from spread of the P/V mutant virus by IFN-I induction. Direct treatment of PM21-NK cells with IFN-I or media from P/V-virus-infected tumor cells enhanced NK cell cytotoxicity, at least in part due to upregulation of the death ligand, TRAIL. IFN-I-treated PM21-NK cells also showed a decrease in IFN-γ secretion, a cytokine we have previously shown to reduce PM21-NK cell tumor killing. Our results highlight multiple mechanisms by which an IFN-I-inducing oncolytic virus can enhance NK-cell-mediated killing of target virus-infected and uninfected tumor cells. Full article

Parainfluenza virus (PIV) infections contribute to the overall childhood morbidity from acute respiratory illness, yet virus-specific epidemiologic data are lacking across many regions globally. Here, we describe the clinical manifestations, seasonality, and meteorologic associations with PIV infections in Ecuadorian children. Between July 2018 and July 2023, we documented demographic and clinical information from children younger than 5 years seen in a single public health clinic with signs and symptoms consistent with an acute respiratory infection. Nasopharyngeal swabs collected at study enrollment underwent multiplex polymerase chain reaction-based diagnostic testing (Biofire FilmArray v. 1.7™). Regional meteorological data from the same period were provided by Ecuador’s Instituto Nacional de Meteorologia e Hidrologia. Parainfluenza viruses were detected in 9% of the 1251 enrolled subjects. PIVs were most frequently detected between March and July, with no change in seasonality following SARS-CoV-2 pandemic onset. Clinical manifestations of PIV infections included non-specific upper respiratory illness (82%), laryngotracheitis (3%), and bronchiolitis (11%). Events of PIV detection were negatively associated with ambient temperature and rainfall. Our findings highlight the contribution that PIVs play in the morbidity associated with pediatric medically attended outpatient respiratory tract infection and provide new insights into the seasonal epidemiology of PIV infections in coastal Ecuador. Full article

RNA viruses pose a significant global public health burden due to their high mutation rates, zoonotic potential, and ability to evade immune responses. A common aspect of their replication is the generation of defective interfering particles (DIPs), which contain truncated defective viral genomes (DVGs) that depend on full-length standard (STD) virus for replication. DVGs have gained recognition as they are increasingly detected in clinical samples from natural infections. While their role in modulating type I interferon (IFN-I) responses is well established, their impact on the complement (C′) system is not understood. In this study, we examined how DVGs influence C′-mediated lysis during parainfluenza virus 5 (PIV5) infection using real-time in vitro cell viability assays. Our results demonstrated that C′ effectively killed human lung epithelial cells infected with STD PIV5, whereas co-infection with DIP-enriched stocks significantly suppressed C′-mediated killing through mechanisms that were dependent on DVG replication but independent of IFN-I production. The titration of DI units in co-infection with STD PIV5 showed a strong linear relationship between DIP-mediated decreases in surface viral glycoprotein expression and the inhibition of C′-mediated lysis. Our findings reveal a previously unrecognized function of DVGs in modulating C′ pathways, shedding light on their potential role in viral persistence and immune evasion. Full article

Acute respiratory infections (ARIs) are a leading cause of death in children under five globally. The seasonal trends and profiles of respiratory viruses vary by region and season. Due to limited information and the population’s vulnerability, we conducted the hospital-based surveillance of respiratory viruses in Eastern Uttar Pradesh. Throat and nasal swabs were collected from outpatients and inpatients in the Department of Paediatrics, Baba Raghav Das (BRD) Medical College, Gorakhpur, between May 2022 and April 2023. A total of 943 samples from children aged 1 to 60 months were tested using multiplex real-time PCR for respiratory viruses in cases of ARI and SARI. Out of 943 samples tested, the highest positivity was found for parainfluenza virus [105 (11.13%) PIV-1 (79), PIV-2 (18), PIV-4 (18)], followed by adenovirus [82 (8.7%), RSV-B, [68 (7.21%)], influenza-A [46(4.9%): H1N1 = 29, H3N2 = 14), SARS CoV-2 [28 (3%)], hMPV [13(1.4%), RSV-A [4 (0.42%), and influenza-B (Victoria lineage) 1 (0.10%). The maximum positivity of respiratory viruses was seen in children between 1 to 12 months. The wide variation in prevalence of these respiratory viruses was seen in different seasons. This study enhances understanding of the seasonal and clinical trends of respiratory virus circulation and co-infections in Eastern Uttar Pradesh. The findings highlight the importance of targeted interventions to reduce the burden of respiratory infections in this region. Full article

Human parainfluenza viruses (hPIVs) are major contributors to respiratory tract infections in young children worldwide. Despite their global significance, genomic surveillance of hPIV1 and hPIV2 had not previously been conducted in Russia. This study aimed to develop a robust amplicon-based sequencing protocol for these viruses. The designed primer sets were tested on clinical samples containing hPIV RNA to evaluate their performance and efficiency. Sequencing results demonstrated high-quality genome data and efficient amplification across various Ct values. As a result, 41 hPIV1 and 13 hPIV2 near-complete genome sequences were successfully obtained from clinical specimens collected in Saint Petersburg (Russia). Phylogenetic analysis of the HN gene sequences showed that Russian hPIV1 strains clustered into clades II and III, while hPIV2 strains were distributed between clusters G1a and G3. The whole-genome-based trees confirmed the same distribution of the strains. These findings highlight the potential of our primer panels and contribute to a better understanding of the molecular characteristics and phylogenetic diversity of circulating hPIV strains. Notably, this study presents the first evolutionary analysis of hPIVs in Russia. Full article

The study highlights the significant changes in respiratory virus epidemiology following the lifting of COVID-19 restrictions. Method: In this single-centre retrospective study, the virological readouts of adenovirus (AdV), influenza virus A (IAV), influenza virus B (IBV), parainfluenza viruses (PIV) 1, 2, 3, 4, respiratory syncytial virus (RSV), and coupled enterovirus and rhinovirus (EV/RV) were extracted from the respiratory specimens of paediatric patients in Hong Kong from January 2015 to February 2024. The subjects were stratified into five age groups. Results: The study included 18,737 and 6001 respiratory specimens in the pre-COVID-19 and post-COVID-19 mask mandate period, respectively. The mean age of hospitalised patients increased from 3.49 y ± 0.03 y to 4.37 y ± 0.05 y after the COVID-19 lockdown. The rates of single-virus infection and co-infection were significantly higher in the post-COVID-19 mask mandate period. The odds ratio for AdV for all age groups (OR: 4.53, 4.03, 2.32, 2.46, 1.31) and RSV in older children from 3 years old and above (OR: 1.95, 3.38, p < 0.01) were significantly elevated after the COVID-19 outbreak. Conclusions: Our findings suggest that public health measures to contain COVID-19 may have unintended consequences on children’s natural exposure and immunity to other respiratory viruses, potentially increasing their morbidity in the post-pandemic era. Full article

The impact of common respiratory virus infections on adults and older individuals in the community is unclear, excluding seasonal influenza viruses. We examined FilmArray® tests performed on 1828 children aged <10 years and 10,803 adults, including cases with few respiratory symptoms, between January 2021 and June 2024. Approximately 80% of the children tested positive for ≥1 viruses, while 9.5% of the adults tested positive mostly for severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). Besides SARS-CoV-2 infection, 66 out of 97 patients (68.0%) aged >60 years with rhinovirus/enterovirus (RV/EV), respiratory syncytial virus (RSV), parainfluenza virus-3 (PIV-3), or human metapneumovirus (hMPV) infection required hospitalization, of whom seven died; 26 out of 160 patients (16.3%) aged <60 years required hospitalization mostly because of deterioration of bronchial asthma, with no reported deaths. In older patients with RV/EV infection, three with few respiratory symptoms died due to worsened heart failure. Although the frequency of common respiratory virus infections in older adults is low, it may be overlooked because of subclinical respiratory symptoms, and its clinical significance in worsening comorbidities in older adults should not be underestimated. Full article

Aim: Respiratory viruses significantly impact public health, contributing to high morbidity and mortality rates in both children and adults. This study evaluates the distribution and incidence of respiratory tract viruses in our hospital from 2019 to 2022, focusing on changes post-COVID-19 pandemic. Material and Methods: Utilizing molecular methods, we analyzed nasopharyngeal swabs with the FTD Respiratory Pathogens 21 kit and the QIAStat Dx Respiratory Panel kit at Istanbul Faculty of Medicine. A total of 1186 viruses were detected in 2488 samples (47.6% of the total) examined with the FTD Respiratory Pathogens 21 kit between 2019 and 2022. Results: It was determined that the detection rates were 52.8% in 2019, 44.3% in 2020, 50.0% in 2021, and 40.0% in 2022. Notable changes in prevalence were observed for pandemic influenza A (IAV-H1N1pdm2009), parainfluenza virus (PIV)-3, rhinovirus (RV), and respiratory syncytial virus (RSV)-A/B (p < 0.05). RV consistently showed the highest detection rates across all years (17.6% to 7.9%). Additionally, 1276 viruses were detected in 1496 samples using the QIAStat DX kit, with 91.3% positivity in 2021 and 78.6% in 2022, highlighting the kit’s effectiveness in rapid diagnosis. Conclusions: This study enhances understanding of respiratory virus epidemiology during and after the pandemic, emphasizing the need for ongoing surveillance and strategic public health measures to address the evolving landscape of respiratory infections. Full article

Background: After the removal of the three-year epidemic control restrictions, Chinese children were confronted with heightened risks of respiratory infections. We aimed to investigate the post-pandemic (2023) epidemiology of respiratory infections among pediatric inpatients in a tertiary hospital in Shanghai, China, and compare it with the pre-pandemic (2019) levels. Methods: A total of 2644 pediatric inpatients were enrolled based on discharge time and divided into group 2019 (n = 1442) and group 2023 (n = 1202). Information on the demographic characteristics, diagnoses, and pathogen test results (Mycoplasma pneumoniae, MP; Chlamydia pneumoniae, CP; Legionella pneumophila, LP; Influenza A, IFA; Influenza B, IFB; Parainfluenza virus, PIV; respiratory syncytial virus, RSV; Coxsackie virus, COX; Adenovirus, ADV; Epstein–Barr virus, EBV) was collected and analyzed. Results: Significant increases were found in the overall test positivity rates (64.6% vs. 46.7%), mixed infection rates (17.4% vs. 9%), and proportion of severe cases (25.5% vs. 3.7%) after the pandemic than those before it. Compared with 2019, the incidences of MP, IFA, LP, RSV, and ADV remarkably increased, while those of IFB and COX decreased, with no obvious differences noted for CP, PIV, and EBV in 2023. A significantly higher MP-positive detection rate was noticed in children aged 1–6 years in 2023 than in 2019. The incidence of RSV infection began to rise in August 2023, earlier than the conventional epidemic season. Conclusions: Compared with the pre-pandemic levels, the overall test positivity rates of atypical pathogens and viruses among pediatric inpatients significantly increased, and alterations in the disease spectrum, epidemic season, and age of prevalence were observed after the COVID-19 pandemic. Full article

Introduction: Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. Methods: We performed a retrospective analysis of results for 13,591 respiratory tract samples for human metapneumovirus (HMPV), influenza virus, parainfluenza virus (PIV) and respiratory syncytial virus (RSV) in immunocompetent and immunosuppressed patients. A seasonal pattern was aligned to the data of immunocompetent patients through a logistic regression model of positive and negative test results. Results: A narrow seasonal pattern (January to March) was documented for HMPV. Most RSV infections were detected in the winter and early spring months, from December to March, but occasional cases of RSV could be found throughout the year. The peak season for PIV-3 was during the summer months, and that for PIV-4 was mostly in autumn. A narrow seasonal pattern emerged for influenza virus as most infections were detected in the winter, in January and February. The seasonal patterns of HMPV, RSV, PIV, and influenza virus were similar for both immunocompetent and immunocompromised patients. Conclusions: We found no difference in the seasonality of HMPV, RSV, PIV, and influenza virus infections between immunosuppressed and immunocompetent hosts. Full article

Background. The emergence of the Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of December 2021 has drastically increased the number of infected children in Japan, along with the number of children with febrile convulsions, but its clinical impact is unclear. Materials and Methods. We compared the frequency of SARS-CoV-2 infection in children hospitalized with febrile convulsions with the frequency of SARS-CoV-2 infection in children with fever and respiratory symptoms without convulsions. Results. In 2021 and 2022, 49 and 58 children required emergency hospitalization for febrile convulsions (FC group) with status epilepticus or cluster spasms, in which 24 and 38 children underwent a Filmarray^® respiratory panel test (FA test), respectively, and others received a quantitative antigen test for SARS-CoV-2. In 2022, only six patients tested positive for SARS-CoV-2 (10.3%, 6/58). As a reference group, 655 children aged <10 years who underwent the FA test for fever and respiratory symptoms during the same period were investigated, and 4 (1.8%, 4/223) and 42 (9.7%, 42/432) tested positive for SARS-CoV-2 in 2021 and 2022, respectively. Rhinovirus/enterovirus (RV/EV) was the most frequently detected virus (40.3%, 264/655), followed by respiratory syncytial virus (RSV) (18.9%, 124/655) and parainfluenza virus 3 (PIV3) (7.8%, 51/655). There was no significant difference in the trend of detected viruses between the two groups. Conclusions. The frequency and severity of febrile convulsions requiring hospitalization associated with SARS-CoV-2 infection of the Omicron strain may be similar to that of other respiratory viruses in children. Full article

There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce³⁺ ↔ Ce⁴⁺) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors. Full article

Ectopic protein overexpression in immortalised cell lines is a commonly used method to screen host factors for their antiviral activity against different viruses. However, the question remains as to what extent such artificial protein overexpression recapitulates endogenous protein function. Previously, we used a doxycycline-inducible overexpression system, in conjunction with approaches to modulate the expression of endogenous protein, to demonstrate the antiviral activity of IFITM1, IFITM2, and IFITM3 against influenza A virus (IAV) but not parainfluenza virus-3 (PIV-3) in A549 cells. We now show that constitutive overexpression of the same IFITM constructs in A549 cells led to a significant restriction of PIV-3 infection by all three IFITM proteins. Variable IFITM mRNA and protein expression levels were detected in A549 cells with constitutive versus inducible overexpression of each IFITM. Our findings show that overexpression approaches can lead to levels of IFITM1, IFITM2, and IFITM3 that significantly exceed those achieved through interferon stimulation of endogenous protein. We propose that exceedingly high levels of overexpressed IFITMs may not accurately reflect the true function of endogenous protein, thus contributing to discrepancies when attributing the antiviral activity of individual IFITM proteins against different viruses. Our findings clearly highlight the caveats associated with overexpression approaches used to screen cellular host proteins for antiviral activity. Full article

RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses. Full article