Parainfluenza Research Articles

The Distribution of Respiratory Viral Pathogens Among the Symptomatic Respiratory Tract Infection Patients From Dhaka City in the Pre-COVID-19 Pandemic Era.

Rapid and accurate diagnosis is crucial for determining the etiology and, perhaps, effectively treating and preventing viral respiratory infections. A multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay⁠⁠⁠⁠⁠⁠⁠ was utilized to determine the prevalence of viral etiology in cases of acute respiratory tract infections (ARTIs). Outpatient department (OPD) and intensive care unit (ICU) patients with fever and respiratory symptoms were enrolled from December 2018 to April 2020. Nucleic acids were extracted from the respiratory tract samples using the SV Total RNA Isolation System (Promega Corporation, Madison, WI), and virus identification was performed using qRT-PCR assay (Fast Track Diagnostics {FTD} Respiratory Pathogens, Esch-sur-Alzette, Luxembourg). A total of 152 samples were collected from OPD and ICU. Among them, 32.23% (n = 49) of the patients were positive for at least one respiratory virus. From 49 infected cases, 42 had only a single viral pathogen, whereas seven had co-infections. Of the patients, 32.25% (30) in the OPD and 32.20% (19) in the ICU tested positive for the respiratory viral pathogen. Among the OPD patients, human coronaviruses (HCoVs) OC43, 229E, NL63, and HKU1were detected as predominant viruses (10.75%), followed by influenza virus (IFV) (8.6%), human rhinoviruses (HRVs) (6.45%), human parainfluenza viruses (HPIVs) (6.45%), respiratory syncytial virus (RSV) (3.22%), and adenovirus (2.15%). In ICU cases, HPIV and HRV were detected as predominant viruses (8.47% each), followed by HCoV (5.08%), human metapneumovirus (HMPV) (5.08%), influenza A virus (IAV) (3.38%), adenovirus (3.38%), and RSV (1.69%). This study highlighted the prevalence of respiratory viruses in both the community and hospital settings during pre-COVID-19, indicating a significant presence among patients in these environments.

Seasonality and Co-Detection of Respiratory Viral Infections Among Hospitalised Patients Admitted With Acute Respiratory Illness-Valencia Region, Spain, 2010-2021.

Respiratory viruses are known to represent a high burden in winter, yet the seasonality of many viruses remains poorly understood. Better knowledge of co-circulation and interaction between viruses is critical to prevention and management. We use > 10-year active surveillance in the Valencia Region to assess seasonality and co-circulation. Over 2010-2021, samples from patients hospitalised for acute respiratory illness were analysed using multiplex real-time PCR to test for 9 viruses: influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV), rhino/enteroviruses (HRV/ENV), metapneumovirus (MPV), bocavirus, adenovirus, SARS-CoV-2 and non-SARS coronaviruses (HCoV). Winter seasonal patterns of incidence were examined. Instances of co-detection of multiple viruses in a sample were analysed and compared with expected values under a crude model of independent circulation. Most viruses exhibited consistent patterns between years. Specifically, RSV and influenza seasons were clearly defined, peaking in December-February, as did HCoV and SARS-CoV-2. MPV, PIV and HRV/ENV showed less clear seasonality, with circulation outside the observed period. All viruses circulated in January, suggesting any pair had opportunity for co-infection. Multiple viruses were found in 4% of patients, with more common co-detection in children under 5 (9%) than older ages. Influenza co-detection was generally observed infrequently relative to expectation, while RSV co-detections were more common, particularly among young children. We identify characteristic patterns of viruses associated with acute respiratory hospitalisation during winter. Simultaneous circulation permits extensive co-detection of viruses, particularly in young children. However, virus combinations appear to differ in their rates of co-detection, meriting further study.

Changes in the Antimicrobial Resistance and Bacterial Epidemiology of Moraxella catarrhalis from Pediatric Community-Acquired Pneumonia Patients During the COVID-19 Pandemic: A 5-Year Study at a Tertiary Hospital of Southwest China.

This study aimed to assess the impact of the COVID-19 pandemic on Moraxella catarrhalis infections in pediatric patients hospitalized with community-acquired pneumonia (CAP). The epidemiological features and antimicrobial resistance (AMR) patterns of M. catarrhalis were compared between the pre-pandemic period (2018-2019) and during the pandemic (2020-2022). The results revealed a marked increase in the positivity rate of M. catarrhalis in 2020 and 2021 compared with the pre-pandemic years. The median age of the patients increased significantly in 2021 and 2022, while the proportion of male patients decreased substantially from 2019 to 2021. In addition, there were notable changes in the co-infections of Haemophilus influenzae, parainfluenza virus, and respiratory syncytial virus during the COVID-19 pandemic. The AMR profile of M. catarrhalis also changed significantly, showing increased resistance to ampicillin, but decreased resistance to trimethoprim-sulfamethoxazole and ofloxacin, and a lower proportion of multidrug-resistant isolates. Notably, ampicillin resistance increased among β-lactamase-producing isolates. Before the pandemic, the number and detection rate of isolates, along with resistance to ampicillin and trimethoprim-sulfamethoxazole, were seasonally distributed, peaking in autumn and winter. However, coinciding with local COVID-19 outbreaks, these indices sharply fell in February 2020, and the number of isolates did not recover during the autumn and winter of 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection landscape of M. catarrhalis in pediatric CAP patients, as evidenced by shifts in the detection rate, demographic characteristics, respiratory co-infections, AMR profiles, and seasonal patterns.

Spectrum of respiratory viruses identified from SARS-CoV-2-negative human respiratory tract specimens in Watansoppeng, Indonesia.

Respiratory infections account for millions of hospital admissions worldwide. The aetiology of respiratory infections can be attributed to a diverse range of pathogens including viruses, bacteria and fungi. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-negative specimens from Wattansoppeng city, South Sulawesi, were analysed to study the spectrum of respiratory viruses. Samples were screened for influenza virus, enterovirus, Paramyxoviridae, Nipah virus, Coronaviridae and Pneumoviridae. Of 210 specimens, 19 were positive for respiratory syncytial virus (RSV)-A, RSV-B, human parainfluenza virus type 1 (HPIV-1), HPIV-2, human rhinovirus (HRV)-A, HRV-B, HRV-C, human metapneumovirus (HMPV), influenza A virus (IAV) and coxsackievirus A6 (CV-A6). Influenza virus was of seasonal H3N2 subtype. The HMPVs were of genotypes B1 and A2a, while one RSV-A was of the ON-1 genotype. The viruses mostly affected children with unknown severity.

Molecular Investigation of Seven Respiratory Viruses in Patients with Acute Respiratory Tract Infections

Introduction: Respiratory tract infection (RTI) is among the important factors that can threaten human health and is one of the most prevalent etiological agents of death, especially in young children. Viruses account for approximately 80% of various RTIs worldwide. Our study aimed to investigate the molecular prevalence of seven respiratory viruses in RTI. Our results can help develop appropriate public health strategies and treatment management of RTIs. Materials and Methods: 120 respiratory samples were obtained from patients with flu-like manifestations from hospitals referred to the Iran University of Medical Sciences during 2020-2022. Nucleic acid extraction was performed, and then real-time polymerase chain reaction was performed to analyze the specimens to investigate seven respiratory viruses. Results: Of the 120 respiratory specimens collected from patients with RTI, viruses were identified in 41 (34.16%) samples, encompassing 24 (40.7%) females and 17 (27.9%) males. SARS-CoV-2 (n = 22, 18.3%) and Parainfluenza virus (n=18, 15%) were the predominant detected viruses in the present study, followed by respiratory syncytial viruses (n=1, 0.8%). Other viruses like Metapneumovirus, Adenovirus, Bocavirus, and Rhinovirus were not found in our study. We could not detect any co-infection in our analysis. Conclusion: SARS-CoV-2 and Parainfluenza-virus were the predominant viruses detected in our study, followed by respiratory syncytial viruses. Other viruses, such as Metapneumovirus, Adenovirus, Bocavirus, and Rhinovirus, have not been found in our study. We could not detect any co-infection in our consideration. This result can help develop appropriate public health strategies, targeting prevention and avoiding inappropriate treatment such as using unnecessary antibiotics.

Viral etiology of febrile respiratory syndrome among patients in Liaoning Province, China

BackgroundFebrile respiratory syndrome (FRS) is often associated with viral infections. The aim of this study was to identify the viral pathogens responsible for FRS in Liaoning Province, China.MethodsWe tested eight respiratory viruses, namely, influenza virus (IFV), rhinovirus (RV), human adenovirus (HAdV), human bocavirus (HBoV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV), using reverse transcription-polymerase chain reaction (RT-PCR). Statistical analyses were performed using SPSS version 25.0, and the data were plotted using RStudio 4.2.1 software.ResultsIFV was the most frequently identified pathogen, followed by RV, HAdV, HBoV, HPIV, HCoV, RSV, and HMPV. RSV/HBoV coinfection occurred most frequently among the mixed cases. The rate of respiratory virus detection was highest in children under one year of age and decreased significantly with age. Seasonal trends showed a peak in virus detection during the winter months.ConclusionsIFV is the leading cause of FRS in Liaoning Province, China, with single-virus infections prevailing over coinfections. Observations indicate a differential virus detection rate across age groups and seasons, highlighting the need for focused preventive strategies to mitigate the transmission of respiratory viruses, particularly among susceptible populations in the colder season.

Effect of Universal Masking on Non-Severe Acute Respiratory Syndrome Coronavirus 2 Healthcare-Associated Respiratory Viral Infections.

Respiratory viral infections are common and are a major cause of morbidity and mortality. We evaluated the impact of universal masking implemented during the coronavirus disease 2019 (COVID-19) pandemic on other healthcare-associated respiratory viral infections (HA-RIs) in an academic medical center. A retrospective cohort study was performed among all inpatients aged ≥18 years admitted between 1 May 2019 and 30 June 2022. Universal masking was implemented in May 2020 at our hospital and state-level mask mandates had been lifted by May 2021. We evaluated and compared the HA-RI rates, adjusted for monthly community-onset viral infections, during the premasking period, universal masking period, and post-community mandate period. We identified 3015 patients (median age, 58 years; 48.0% males) with a positive respiratory viral test within 14 days prior to, or during, their hospitalization; 441 (14.6%) patients had an HA-RI. Rhinovirus/enterovirus (51.0%), parainfluenza virus (14.3%), coronaviruses (229E, OC43, HKU1, and NL63; 13.2%) and influenza (10.0%) were the predominant HA-RI viruses detected. The monthly HA-RI rate decreased 34.9% (95% confidence interval, 8.8%-51.8%) after the implementation of universal masking (0.71 premasking period vs 0.19 universal masking period vs 0.35 infections per 1000 patient-days in the post-community mandate period) while accounting for a drop in the community-onset respiratory viral infections using a structural time-series model analysis (P < .001), with no significant change in HA-RI rates with the relaxation of community masking mandate. Implementation of universal masking at our hospital was associated with a significantly reduced incidence of HA-RIs.

Similarity analyses of causative viruses for chronic obstructive pulmonary disease and asthma exacerbations

BackgroundThe representativeness of cohort studies compared to nationwide data is a major concern. This study evaluated the similarity and seasonality of causative respiratory viruses for chronic obstructive pulmonary disease (COPD) and asthma exacerbations between retrospective multicenter cohort study and nationwide data.MethodsWe compared data from the retrospective multicenter cohort study with Korean Influenza and Respiratory Surveillance System data between 2015 and 2018. Correlation, dynamic time warping (DTW), and seasonal autoregressive integrated moving average (SARIMA) analyses were performed.ResultsSpearman correlation coefficients [ρ] indicated very strong (respiratory syncytial virus [RSV] [ρ = 0.8458] and influenza virus [IFV] [ρ = 0.8272]), strong (human metapneumovirus [HMPV] [ρ = 0.7177] and parainfluenza virus [PIV] [ρ = 0.6742]), and moderate (rhinovirus [RV] [ρ = 0.5850] and human coronavirus [HCoV] [ρ = 0.5158]) correlations. DTW analyses showed moderate (PIV) and high (IFV, RSV, and HMPV) synchronicity between the two datasets, while RV and HCoV showed low synchronicity. SARIMA analyses revealed 12-month seasonality for IFV, RSV, PIV, and HMPV. The peak season was winter for RSV and IFV, spring to summer for PIV, and spring for HMPV.ConclusionsThis was the first study to report the synchronicity between a retrospective multicenter cohort study of viruses that can cause COPD or asthma exacerbations and nationwide surveillance system data.

Analysis of neuraminidase activity of human parainfluenza viruses using enzyme-linked lectin assay and BTP3-Neu5Ac assay.

Human parainfluenza viruses (hPIVs) are causative agents of upper and lower respiratory tract infections and they have four serotypes. The virion surface displays hemagglutinin-neuraminidase (HN), having hemagglutinating (HA) and neuraminidase (NA) activities in a single molecule. The HA activity binds the virion to sialic acid on the viral receptor on host cells and the NA releases the progeny viruses from the cell surface. There are several methods for assaying viral NA activity, such as the thiobarbituric acid assay, 4-methylumbelliferyl-N-acetyl-α-d-neuraminic acid assay, NA-Star assay, and enzyme-linked lectin assay (ELLA). However, these are mainly used for influenza viruses and not for hPIVs. A fluorescent-based cytochemical NA assay using BTP3-Neu5Ac as the substrate was recently developed and used for orthomyxo- and paramyxoviruses, including types 1 and 3 hPIVs. In this study, we used the ELLA, and BTP-Neu5Ac assay for 14 field isolate strains of hPIVs including all four serotypes. The reaction in ELLA at pH 6.5 using peanut agglutinin (PNA) as a lectin was very low for all tested viruses except a type 3 virus strain with the maximum reaction at pH 6.5 and the acidic conditions did not enhance the reaction. ELLA with another lectin, Erythrina cristagalli agglutinin exhibited significant and stronger reactions than with PNA in some strains of types 1 and 3 viruses. The BTP3-Neu5Ac assay showed a fluorescent signal on cells infected with all the viruses except the hPIV1/Sendai/713/2018 strain in LLC-MK2 and/or MNT-1. The signal was detected in cell-free virus, as well, in all the viruses except the hPIV4a/Sendai/3935/2003 strain. The strength of the signal varied among viral strains but it was stronger in the reaction at pH 4.0 than pH 7.0 and strongest in type 2 hPIVs.

Respiratory viral infections in bone marrow transplant patients: insights from a tertiary care hospital in Rawalpindi, Pakistan.

To determine the incidence of respiratory viral infections in bone marrow transplant patients. The prospective, descriptive, cross-sectional study was conducted at a tertiary care hospital in Rawalpindi, Pakistan, from September 2019 to August 2020, and comprised respiratory specimens from recipients of haematopoietic stem cell transplant. The specimens were collected in viral transport medium, and were then taken to the Department of Virology. Multiplex polymerase chain reaction was performed on the specimens to ascertain the incidence and prevalence of respiratory viruses. Data was analysed using SPSS 24. Of the 85 subjects, 53(62.35%) were males and 32(37.65%) were females. The overall median age was 20.0 years (interquartile range: 11.0-32.0 years). Respiratory viral infections were detected in 31(36.4%) specimens. Among them, human rhinovirus was detected in 12(38.7%) cases, respiratory syncytial virus in 5(16.1%), influenza A/H3 in 4(13%), human parainfluenza virus-1 in 3(9.7%), adenovirus in 2(6.4%), human parainfluenza virus-3 in 1(3.2%), human parainfluenza virus-4 in 1(3.2%) and human metapneumovirus in 1(3.2%) case. There were 2(6.4%) cases of co-infection. More than one-third recipients of haematopoietic stem cell transplant were found to have respiratory viral infections, highlighting the importance of employing multiplex respiratory polymerase chain reaction in early diagnosis and treatment of such infections.

Post-Pandemic Epidemiology of Respiratory Infections among Pediatric Inpatients in a Tertiary Hospital in Shanghai, China.

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. 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. 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. 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.

Epidemiology of respiratory viruses before and during the COVID-19 pandemic in a tertiary care hospital in Southern Brazil

BackgroundRespiratory viral infections affect millions of people worldwide and are life threatening for many of them. The viral seasonality leads to changes in the dynamics of respiratory infections and the importance of monitoring and surveillance of respiratory viruses becomes clearer. ObjectivesThis study aims to analyze data from respiratory virus testing at the Hospital de Clínicas de Porto Alegre (HCPA) to evaluate their epidemiology from 2018 to 2021, observing their occurrence and seasonality before and after the onset of the SARS-CoV-2 pandemic. Study designIn this study, data analysis was divided into four time periods, corresponding to 2018 to 2021. Anonymized patients diagnosed with influenza virus (FLU), human parainfluenza virus (HPIV), human respiratory syncytial virus (HRSV), SARS-CoV-2 virus, or human adenovirus (HAdV) were included. We conducted chi-square goodness-of-fit tests for each virus by year, and a p-value of <0.05 was considered statistically significant. ResultsAll analyzed respiratory viruses presented reduced case numbers during the COVID-19 pandemic, except FLU, which showed an increase of four cases in 2021 compared to 2019. For most viruses, the lowest incidence of confirmed cases was found in 2020. Furthermore, when excluding SARS-CoV-2, HRSV presented the most positive cases during the studied period, except in 2020. Besides SARS-CoV-2, the FLU was the only other respiratory virus that recorded deaths. It was also possible to observe that the number of SARS-CoV-2 cases reduced from April 2021. ConclusionsWe observed that most respiratory tract viral infections decreased during the COVID-19 pandemic, and this result may be associated with the public interventions for containing the COVID-19 pandemic. Moreover, the reduction of these other viruses may have resulted from the measures for prevention conducted by HCPA.

STING Agonist Induced Innate Immune Responses Drive Anti-Respiratory Virus Activity In Vitro with Limited Antiviral Efficacy In Vivo.

The emergence of SARS-CoV-2 and seasonal outbreaks of other respiratory viruses highlight the urgent need for broad-spectrum antivirals to treat respiratory tract infections. Stimulator of interferon genes (STING) is a key component of innate immune signaling and plays a critical role in protection of the host against viral infections. Previously the STING agonist diABZI-4, a diamidobenzimidazole-based compound, demonstrated protection against SARS-CoV-2 both in vitro and in vivo. However, its broad-spectrum antiviral activity against other respiratory viruses in human airway epithelial cells, which are the primary targets of these infections, is not well established. In this study, we demonstrated that diABZI-4 stimulated robust innate immune responses protecting lung cells against a wide range of respiratory viruses, including influenza A virus (IAV), common cold coronaviruses, SARS-CoV-2, human rhinovirus (HRV), and human parainfluenza virus. diABZI-4 was highly active in physiologically relevant human airway epithelial tissues grown at the air-liquid interface, blocking replication of IAV, SARS-CoV-2, and HRV in these tissues. Furthermore, treatment of macrophages with diABZI-4 resulted in the secretion of cytokines that protected the primary airway epithelial cells from IAV infection. Despite the promising in vitro pan-antiviral activity, intranasal administration of diABZI-4 in mice provided early, but not sustained, inhibition of IAV replication in the lungs. These data highlight the complexities of the relationship between timing of STING agonist-driven inflammatory responses and viral replication dynamics, emphasizing the development challenge posed by STING agonists as potential therapeutics against respiratory viruses.

The role of respiratory infections in the formation of airway hyperresponsiveness in children

Airway hyperresponsiveness (AHR) is a heterogeneous and complex disorder characterized by excessive narrowing of the airways in response to various exogenous and endogenous stimuli. This article presents information from the last five years, including 50 publications from PubMed and Google Scholar, on the most common viruses that provoke the development of airway hyperresponsiveness in children, including respiratory syncytial virus, rhinovirus, metapneumovirus, influenza and parainfluenza viruses, SARS-CoV-2 coronavirus, adenovirus, and bocavirus. It describes a number of pathophysiological mechanisms by which viruses damage the respiratory epithelium and lead to the formation of infectious and post-infectious bronchial hypersensitivity. The role of hyperexpression of cytokines and inflammatory mediators in the development of AHR, especially in early childhood, is emphasized. It is shown that the inflammatory process and a balanced immune response are crucial for mitigating the severity of the disease caused by viruses. Understanding the molecular mechanisms of inflammatory reactions and the immune response to acute respiratory viral infections can help develop more effective methods for the prevention and treatment of respiratory diseases in children.

A robust mouse model of HPIV-3 infection and efficacy of GS-441524 against virus-induced lung pathology

Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory tract infections. There are no convenient small-animal infection models. Here, we show viral replication in the upper and lower airways of AG129 mice (double IFNα/β and IFNγ receptor knockout mice) upon intranasal inoculation. By multiplex fluorescence RNAscope and immunohistochemistry followed by confocal microscopy, we demonstrate viral tropism to ciliated cells and club cells of the bronchiolar epithelium. HPIV-3 causes a marked lung pathology. No virus transmission of the virus was observed by cohousing HPIV-3-infected AG129 mice with other mice. Oral treatment with GS-441524, the parent nucleoside of remdesivir, reduced infectious virus titers in the lung, with a relatively normal histology. Intranasal treatment also affords an antiviral effect. Thus, AG129 mice serve as a robust preclinical model for developing therapeutic and prophylactic strategies against HPIV-3. We suggest further investigation of GS-441524 and its prodrug forms to treat HPIV-3 infection in humans.

Epidemiology and genetic characterization of human parainfluenza virus-1 infection in pediatric patients from Hangzhou China, 2021–2022

BackgroundHuman parainfluenza virus-1 (HPIV-1) is a notable pathogen instigating acute respiratory tract infections in children. The article is to elucidate the epidemiological and genetic characteristics of HPIV-1 circulating in Hangzhou during the period of 2021–2022.MethodsA cohort of 2360 nasopharyngeal swabs were amassed and subsequently examined via RT-PCR, with HPIV-1 positive samples undergoing P gene sequencing.ResultsThe highest HPIV-1 infection rates were found in children aged between 3 and 6 years. A pronounced positive rate persisted through the latter half of 2021, with a notable decline observed in the initial half of 2022. All HPIV-1 strains could be clustered into 2 groups: Cluster 1, with strains similar to those found in Japan (LC764865, LC764864), and Cluster 2, with strains similar to the Beijing strain (MW575643).ConclusionIn conclusion, our study contributes to the comprehensive data on the epidemiological and genetic characteristics of HPIV-1 in pediatric patients from Hangzhou, post the COVID-19 peak.

Respiratory Viral Testing Rate Patterns in Young Children Attending Tertiary Care Across Western Australia: A Population-Based Birth Cohort Study.

An understanding of viral testing rates is crucial to accurately estimate the pathogen-specific hospitalisation burden. We aimed to estimate the patterns of testing for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV) and human metapneumovirus (hMPV) by geographical location, age and time in children <5 years old in Western Australia. We conducted a population-based cohort study of children born between 1 January 2010 and 31 December 2021, utilising linked administrative data incorporating birth and death records, hospitalisations and respiratory viral surveillance testing records from state-wide public pathology data. We examined within-hospital testing rates using survival analysis techniques and identified independent predictors of testing using binary logistic regression. Our dataset included 46,553 laboratory tests for RSV, influenza, PIV, or hMPV from 355,021 children (52.5% male). Testing rates declined in the metropolitan region over the study period (RSV testing in infants: from 242.11/1000 child-years in 2012 to 155.47/1000 child-years in 2018) and increased thereafter. Conversely, rates increased in non-metropolitan areas (e.g., RSV in Goldfields: from 364.92 in 2012 to 504.37/1000 child-years in 2021). The strongest predictors of testing were age <12 months (adjusted odds ratio [aOR] = 2.25, 95% CI 2.20-2.31), preterm birth (<32 weeks: aOR = 2.90, 95% CI 2.76-3.05) and remote residence (aOR = 0.77, 95% CI 0.73-0.81). These current testing rates highlight the potential underestimation of respiratory virus hospitalisations by routine surveillance and the need for estimation of the true burden of respiratory virus admissions.

Analyzing infections caused by 11 respiratory pathogens in children: Pre‐ and post‐COVID‐19 pandemic trends in China

AbstractWith the lifting of coronavirus disease 2019 (COVID‐19) restrictions in December 2022 in China, the population was widely infected with COVID‐19. We aim to analyzed changes in the epidemiological characteristics of other respiratory pathogens in children before and after the COVID‐19 pandemic. We conducted a retrospective analysis of 44 704 children with acute respiratory infections who underwent 11 respiratory pathogen tests based on multiplex polymerase chain reaction between February and December in both 2022 and 2023. The total pathogen detection rate (24861, 74.80% vs. 6423, 56.01%; p = 0.000) and detection rates of coinfection (4059, 12.21% vs. 676, 5.89%; p = 0.000) in 2023 was significantly higher than that in 2022. The detection rates of influenza A (2567, 7.72% vs. 222, 1.94%; p = 0.000), influenza B (383, 1.15% vs. 37, 0.32%; p = 0.000), human parainfluenza virus (2175, 6.54% vs. 602, 5.25%; p = 0.000), human metapneumovirus (1354, 4.07% vs. 346, 3.01%; p = 0.000), respiratory syncytial virus (3148, 9.47% vs. 870, 7.59%; p = 0.000), and Mycoplasma pneumonia (MP; 9494, 28.56% vs. 1790, 15.61%; p = 0.000) in 2023 were significantly higher than those in 2022, whereas the detection rates of human adenovirus (1124, 3.38% vs. 489, 4.26%; p = 0.000) and human bocavirus (629, 1.89% vs. 375, 3.27%; p = 0.000) were significantly lower than those in 2022. Chlamydia, human rhinovirus, and human coronavirus showed similar detection rates between 2023 and 2022. In 2023, the influenza virus and human parainfluenza virus regained seasonal characteristic, an outbreak of MP infection occurred, the epidemic season of respiratory syncytial virus changed, and the proportion of children with acute respiratory infection aged 0–28 days and over 3 years old increased. Influenza B, metapneumovirus, and human bocavirus were detected in children aged 0–28 days in 2023, but not in 2022. After the COVID‐19 pandemic, we should be alert to the increase of respiratory diseases and the change of epidemic season and susceptible age.

Comparison of clinical characteristics and severity of COVID-19 with or without viral co-infection in hospitalized children

BackgroundCo-infection with other pathogens can alter the severity and clinical outcomes of viral infections. However, the information regarding viral co-infections in pediatric coronavirus disease 2019 (COVID-19) cases is still limited. MethodsThis is a nationwide, retrospective cohort study using the data from the COVID-19 Registry Japan. The pediatric (<18 years), laboratory confirmed, hospitalized COVID-19 patients in the Omicron variant of concern predominant period (January 2022 to January 2024) were included. Co-infection was investigated by multiplex PCR. We compared clinical characteristics, symptoms, severity, and outcomes between children with and without co-infection. ResultsAmong 245 hospitalized pediatric COVID-19 patients, 78 (31.8 %) had co-infections. The patient backgrounds of the “co-infection” and “SARS-CoV-2 alone” groups were similar, although age distribution was different, with a lower number of patients over 12 years in the co-infection group (n = 2, 2.6 % vs. n = 29, 17.4 %; P < 0.001). Among the patients with co-infection, the most common pathogen was enterovirus/rhinovirus (51.3 %), followed by parainfluenza virus (23.1 %) and adenovirus (12.8 %). Patients with co-infection more commonly had respiratory symptoms, including SpO2 < 96 %, shortness of breath, runny nose, and wheezing. Requirement of non-invasive oxygen support was higher in the co-infection group (n = 27, 34.6 % vs. n = 28, 16.8 %, P = 0.006). By multivariable logistic regression analysis, co-infection and presence of any comorbidity were identified as significant risk factors for necessity of oxygen therapy (odds ratio [95 % confidence interval] 2.44 [1.29–4.63] and 3.99 [2.07–7.82], respectively). ConclusionsViral co-infection may increase the risk of respiratory distress in pediatric COVID-19 patients.

Liquid-liquid phase inclusion bodies in acute and persistent parainfluenaza virus type 5 infections.

Cytoplasmic inclusion bodies (IBs) are a common feature of single-stranded, non-segmented, negative-strand RNA virus (Mononegavirales) infections and are thought to be regions of active virus transcription and replication. Here we followed the dynamics of IB formation and maintenance in cells infected with persistent and lytic/acute variants of the paramyxovirus, parainfluenza virus type 5 (PIV5). We show that there is a rapid increase in the number of small inclusions bodies up until approximately 12 h post-infection. Thereafter the number of inclusion bodies decreases but they increase in size, presumably due to the fusion of these liquid organelles that can be disrupted by osmotically shocking cells. No obvious differences were observed at these times between inclusion body formation in cells infected with lytic/acute and persistent viruses. IBs are also readily detected in cells persistently infected with PIV5, including in cells in which there is little or no ongoing virus transcription or replication. In situ hybridization shows that genomic RNA is primarily located in IBs, whilst viral mRNA is more diffusely distributed throughout the cytoplasm. Some, but not all, IBs show incorporation of 5-ethynyl-uridine (5EU), which is integrated into newly synthesized RNA, at early times post-infection. These results strongly suggest that, although genomic RNA is present in all IBs, IBs are not continuously active sites of virus transcription and replication. Disruption of IBs by osmotically shocking persistently infected cells does not increase virus protein synthesis, suggesting that in persistently infected cells most of the virus genomes are in a repressed state. The role of IBs in PIV5 replication and the establishment and maintenance of persistence is discussed.