Investigating epidemiological distribution (temporality and intensity) of respiratory pathogens following COVID-19 de-escalation process in Catalonia, September 2016-June 2021: Analysis of regional surveillance data.

BACKGROUND: Following the low incidence rates of non-SARS-CoV-2 respiratory viruses registered during the strict lockdown enforced in the pandemic, a resurgence of several endemic viruses in Catalonia (Spain) was noted during the early summer of 2021. OBJECTIVES: In this study, we investigated whether the circulation of non-SARS-CoV-2 respiratory viruses in Catalonia, assessed by Microbiological Reporting System of Catalonia (MRSC) and the Epidemiological Surveillance Network of Catalonia, was affected by the strict lockdown measures, as well as, the implication of the Coronavirus Disease 19 (COVID-19) de-escalation process in the late season outbreaks registered during the 2020-2021 season. STUDY DESIGN: A retrospective comparison of epidemic patterns in the respiratory viruses' incidence, using regional public health surveillance data from MRSC, was performed between weeks 26/2016 to week 27/2021. Data were expressed as the weekly total number of test positivity for individual viruses. A segmented negative binomial regression model was conducted, with two parameters included (level and trend) for each segment of the time series (2020 pre-lockdown, 2020 post-lockdown and 2021). Results were reported as a unit changed in the strict lockdown. RESULTS: A total of 51588 confirmed cases of the different respiratory viruses were included in the analysis, the majority were influenza cases (63.7%). An immediate reduction in the weekly number of cases was observed in 2020 after the COVID-19 outbreak for human adenovirus virus (HAdV) (ß2 = -2.606; P <0.01), human parainfluenza virus (HPIV) (ß2 = -3.023; P <0.01), influenza virus (IFV) (ß2 = -1.259; P <0.01), but not for respiratory syncytial virus (RSV), where the number of cases remained unchanged. During 2020, a significant negative trend was found for RSV (ß3 = -0.170, P <0.01), and a positive trend for HAdV (ß3 = 0.075, P <0.01). During 2021, a significant reduction in the weekly number of cases was also observed for all respiratory viruses, and a borderline non-significant reduction for HPIV (ß3 = -0.027; P = 0.086). Moreover, significant positive trends were found for each viral pathogen, except for influenza during 2020-2021 season, where cases remained close to zero. The respiratory viruses increased activity and their late season epidemic start particularly affected children under 6 years old. CONCLUSIONS: Our data not only provides evidence that occurrence of different respiratory virus infections was affected by the strict lockdown taken against SARS-CoV-2 but it also shows a late resurgence of seasonal respiratory viruses' cases during the 2020-2021 season following the relaxation of COVID-19-targeted non-pharmaceutical interventions.

Genetic analysis of human parainfluenza type 2 virus in Riyadh, Saudi Arabia.

The extensive mass gathering of pilgrims from all over the world, as well as the constant flow of foreign workers via country entry crossings, raises the likelihood of respiratory virus outbreaks spreading and evolving in Saudi Arabia. Here, we report the sequence and phylogenetic analysis of the human parainfluenza type-2 (HPIV-2) in nasopharyngeal aspirates (NPAs) collected from Riyadh, Saudi Arabia, from 2020/21 to 2021/22 seasons. RNA was extracted from the clinical samples and subjected to RT-PCR analysis for the detection of IAV and IBV. The full-length HN gene of HPIV-2 was amplified and sequenced. Multiple sequence alignments (both nucleotides and deduced amino acids) were aligned using Clustal W, MegAlign program of Lasergene software, and MEGA 7.0. HPIV-2 was found in (4; 2% of 200) NPAs. Sequence and phylogenetic analysis results showed that indicated a genotype shifting from G3 to G4a with 83% sequence homology 62-M786 from Japan, which was prominent throughout the winter seasons of 2008/09. Multiple amino acid sequence alignment revealed 25 sites of possible difference between G3 genotypes and G4a. A total of twenty- two of these locations were shared by the other G4a genotypes, whereas three positions, 67 V, 175 S, and 377Q, were exclusively shared by G3. Only eight conserved N-glycosylation sites were found at amino acids 6(NLS), 286(NTT), 335(NIT), 388(NNS), 498(NES), 504(NPT), 517(NTT), and 539(NGT) in four Riyadh isolates. Our findings also revealed that the G4a genotype of HPIV-2 predominated in our samples population during the winter seasons of 2020/21 and 2021/22. Further research with a larger sample size covering numerous regions of Saudi Arabia throughout different epidemic seasons is needed to achieve an improved knowledge of HPIV-2 circulation.

[Analysis of parainfluenza virus infection in acute respiratory tract infection adult cases in Shanghai, 2015-2021].

Objective: To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV. Methods: Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR. Results: A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant (χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions: There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.

Clinical impact of human parainfluenza virus infections before and during the COVID-19 pandemic in Southern China.

Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory tract infections (ARTIs). Non-pharmaceutical interventions (NPIs) were widely administered to combat the pandemic of the coronavirus disease 2019 (COVID-19). Respiratory specimens were obtained from 10,454 hospitalized children with ARTIs to detect HPIV. We investigated differences in epidemiological and clinical characteristics of HPIV infections before (2017-2019) and during the COVID-19 pandemic (2020-2022). HPIVs were detected in 392 (3.75%, 392/10,454) patients, of whom 70 (17.86%), 48 (12.24%), and 274 (69.90%) were positive for HPIV1, HPIV2, and HPIV3, respectively. Detection rates of HPIV3 were higher in 2020-2022 than in 2017-2019 (3.38% vs. 2.24%). The seasonal distribution of HPIV1 showed no difference, but HPIV3 peaked between September and December during the COVID-19 pandemic, which differed from previous epidemiological patterns. Compared to the period before the COVID-19 pandemic, there has been a noticeable decrease in the incidence of asthma, moist rales, and emesis in patients infected with HPIV1 and in asthma, expectoration, and severe pneumonia in patients infected with HPIV3 during 2020-2022. The detection rates of HPIV increased in Southern China during the COVID-19 outbreak, which underlines the importance of continuous surveillance of HPIV in the next epidemic season.

Structure-based design of a single-chain triple-disulfide-stabilized fusion-glycoprotein trimer that elicits high-titer neutralizing responses against human metapneumovirus.

The Pneumoviridae family of viruses includes human metapneumovirus (HMPV) and respiratory syncytial virus (RSV). The closely related Paramyxoviridae family includes parainfluenza viruses (PIVs). These three viral pathogens cause acute respiratory tract infections with substantial disease burden in the young, the elderly, and the immune-compromised. While promising subunit vaccines are being developed with prefusion-stabilized forms of the fusion glycoproteins (Fs) of RSV and PIVs, for which neutralizing titers elicited by the prefusion (pre-F) conformation of F are much higher than for the postfusion (post-F) conformation, with HMPV, pre-F and post-F immunogens described thus far elicit similar neutralizing responses, and it has been unclear which conformation, pre-F or post-F, would be the most effective HMPV F-vaccine immunogen. Here, we investigate the impact of further stabilizing HMPV F in the pre-F state. We replaced the furin-cleavage site with a flexible linker, creating a single chain F that yielded increased amounts of pre-F stabilized trimers, enabling the generation and assessment of F trimers stabilized by multiple disulfide bonds. Introduced prolines could increase both expression yields and antigenic recognition by the pre-F specific antibody, MPE8. The cryo-EM structure of a triple disulfide-stabilized pre-F trimer with the variable region of antibody MPE8 at 3.25-Å resolution confirmed the formation of designed disulfides and provided structural details on the MPE8 interface. Immunogenicity assessments in naïve mice showed the triple disulfide-stabilized pre-F trimer could elicit high titer neutralization, >10-fold higher than elicited by post-F. Immunogenicity assessments in pre-exposed rhesus macaques showed the triple disulfide-stabilized pre-F could recall high neutralizing titers after a single immunization, with little discrimination in the recall response between pre-F and post-F immunogens. However, the triple disulfide-stabilized pre-F adsorbed HMPV-directed responses from commercially available pooled human immunoglobulin more fully than post-F. Collectively, these results suggest single-chain triple disulfide-stabilized pre-F trimers to be promising HMPV-vaccine antigens.

Influence of COVID-19 pandemic on the virus spectrum in children with respiratory infection in Xuzhou, China: a long-term active surveillance study from 2015 to 2021.

BACKGROUND: To investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the prevalence of respiratory viruses among pediatric patients with acute respiratory infections in Xuzhou from 2015-2021. METHODS: Severe acute respiratory infection (SARI) cases in hospitalized children were collected from 2015-2021 in Xuzhou, China. Influenza virus(IFV), respiratory syncytial virus (RSV), human parainfluenza virus type 3(hPIV-3), human rhinovirus (hRV), human adenovirus(hAdV), human coronavirus(hCoV) were detected by real-time fluorescence polymerase chain reaction(RT-qPCR), and the results were statistically analyzed by SPSS 23.0 software. RESULTS: A total of 1663 samples with SARI were collected from 2015-2021, with a male-to-female ratio of 1.67:1 and a total virus detection rate of 38.5% (641/1663). The total detection rate of respiratory viruses decreased from 46.2% (2015-2019) to 36% (2020-2021) under the control measures for COVID-19 (P < 0.01). The three viruses with the highest detection rates changed from hRV, RSV, and hPIV-3 to hRV, RSV, and hCoV. The epidemic trend of hPIV-3 and hAdV was upside down before and after control measures(P < 0.01); however, the epidemic trend of RV and RSV had not changed from 2015 to 2021(P > 0.05). After the control measures, the detection rate of hPIV-3 decreased in all age groups, and the detection rate of hCoV increased in all except the 1 ~ 3 years old group. CONCLUSIONS: Implementing control measures for COVID-19 outbreak curbed the spread of respiratory viruses among children as a whole. However, the epidemic of RV and RSV was not affected by the COVID-19 control policy.

Dynamics of parainfluenza virus among hospitalized children with acute respiratory tract infection under two-child policy and COVID-19 pandemic in Hubei Province, China, 2014-2022.

To analyze changes in the detection of parainfluenza virus (PIV) in children hospitalized with acute respiratory tract infection (ARTI) during 2014-2022 in Hubei Province, and explore the impact of the universal two-child policy and the public health measures against COVID-19 epidemic on the prevalence of PIV in China. The study was conducted at the Maternal and Child Health Hospital of Hubei Province. Children aged <18 years with ARTI admitted from January 2014 to June 2022 were enrolled. The infection of PIV was confirmed by the direct immunofluorescence method in nasopharyngeal specimens. Adjusted logistic regression models were used to analyze the influence of the universal two-child policy implementation and public health measurements against COVID-19 on PIV detection. Totally 75 128 inpatients meeting the criteria were enrolled in this study from January 2014 to June 2022 with an overall PIV positive rate of 5.5%. The epidemic seasons of PIV prevalence lagged substantially in 2020. A statistically significant higher positive rate of PIV was observed in 2017-2019 compared to that in 2014-2015 (6.12% vs 2.89%, risk ratio = 2.12, p < 0.001) after the implementation of the universal two-child policy in 2016. A steep decline occurred in PIV positive rate during the COVID-19 epidemic in 2020 (0.92% vs 6.92%, p < 0.001) and it rebounded during the regular epidemic prevention and control period in 2021-2022 (6.35%, p = 0.104). In Hubei Province, the implementation of the universal two-child policy might have led to an increase of PIV prevalence, and public health measures during the COVID-19 epidemic might have influenced the fluctuation in PIV detection since 2020.

Clinical characteristics of hospitalized children with community-acquired pneumonia and respiratory infections: Using machine learning approaches to support pathogen prediction at admission.

BACKGROUND: Acute respiratory infections (ARIs) are common in children. We developed machine learning models to predict pediatric ARI pathogens at admission. METHODS: We included hospitalized children with respiratory infections between 2010 and 2018. Clinical features were collected within 24 h of admission to construct models. The outcome of interest was the prediction of 6 common respiratory pathogens, including adenovirus, influenza virus types A and B, parainfluenza virus (PIV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP). Model performance was estimated using area under the receiver operating characteristic curve (AUROC). Feature importance was measured using Shapley Additive exPlanation (SHAP) values. RESULTS: A total of 12,694 admissions were included. Models trained with 9 features (age, event pattern, fever, C-reactive protein, white blood cell count, platelet count, lymphocyte ratio, peak temperature, peak heart rate) achieved the best performance (AUROC: MP 0.87, 95% CI 0.83-0.90; RSV 0.84, 95% CI 0.82-0.86; adenovirus 0.81, 95% CI 0.77-0.84; influenza A 0.77, 95% CI 0.73-0.80; influenza B 0.70, 95% CI 0.65-0.75; PIV 0.73, 95% CI 0.69-0.77). Age was the most important feature to predict MP, RSV and PIV infections. Event patterns were useful for influenza virus prediction, and C-reactive protein had the highest SHAP value for adenovirus infections. CONCLUSION: We demonstrate how artificial intelligence can assist clinicians identify potential pathogens associated with pediatric ARIs upon admission. Our models provide explainable results that could help optimize the use of diagnostic testing. Integrating our models into clinical workflows may lead to improved patient outcomes and reduce unnecessary medical costs.

The epidemiological features of respiratory tract infection using the multiplex panels detection during COVID-19 pandemic in Shandong province, China.

Respiratory tract infection is one of the most common reasons for both morbidity and mortality worldwide. High attention has been paid to the etiological tracing of respiratory tract infection since the advent of COVID-19. In this study, we aimed to evaluate the epidemiological features of pathogens in respiratory tract infection, especially during COVID-19 pandemic. A total of 7668 patients with respiratory tract infection who admitted to Qilu Hospital of Shandong University from March 2019 to Dec 2021 were retrospectively included. The respiratory tract specimens were detected using a commercial multiplex PCR-based panel assay for common respiratory pathogens including influenza A virus (Flu-A), influenza A virus H1N1 (H1N1), influenza A virus H3N2 (H3N2), influenza B virus (Flu-B), parainfluenza virus (PIV), respiratory syncytial virus (RSV), adenovirus (ADV), Boca virus (Boca), human Rhinovirus (HRV), Metapneumovirus (MPV), Coronavirus (COV), Mycoplasma pneumoniae (MP), and Chlamydia (Ch). The positive rates were compared using a chi-square test. Compared with 2019, the positive rate of pathogen detection during from January 2020 to December 2021 was significantly lower, especially the detection of Flu-A. The positive rate of respiratory pathogen strains was 40.18% during COVID-19 pandemic, and a total of 297 cases (4.69%) of mixed infection with two or more pathogens were detected. There was no statistical difference in the positive rate between male and female patients. However, the positive rates of infection were different among different age groups, with higher incidence of RSV in infancy and toddler group, and MP infection in children and teenager group. While, HRV was the most common pathogen in the adult patients. Moreover, Flu-A and Flu-B were higher in winter, and MP and RSV were higher in spring, autumn and winter. The pathogens such as ADV, BOCA, PIV, and COV were detected without significant seasonal distribution. In conclusion, respiratory pathogen infection rates may vary by age and season, regardless of gender. During the COVID-19 epidemic, blocking transmission routes could help reduce the incidence of respiratory tract infection. The current prevalence of respiratory tract infection pathogens is of great significance for clinical prevention, diagnosis and treatment.

Characterization of viral pathogens associated with symptomatic upper respiratory tract infection in adults during a low COVID-19 transmission period.

Background: The epidemiology of respiratory tract infections (RTI) has dramatically changed over the course of the COVID-19 pandemic. A major effort in the clinical management of RTI has been directed toward diagnosing COVID-19, while the causes of other, common community RTI often remain enigmatic. To shed light on the etiological causes of RTI during a low COVID-19 transmission period in 2021, we did a pilot study using molecular testing for virologic causes of upper RTI among adults with respiratory symptoms from Almaty, Kazakhstan. Methods: Adults presenting at two public hospitals with respiratory symptoms were screened using SARS-CoV-2 PCR on nasopharyngeal swabs. A subset of RTI+, COVID-19-negative adults (n = 50) was then tested for the presence of common RTI viruses and influenza A virus (IAV). Next generation virome sequencing was used to further characterize the PCR-detected RTI pathogens. Results: Of 1,812 symptomatic adults, 21 (1.2%) tested SARS-CoV-2-positive. Within the COVID-19 negative outpatient subset, 33/50 subjects (66%) had a positive PCR result for a common community RTI virus, consisting of human parainfluenza virus 3-4 (hPIV 3-4) in 25/50 (50%), rhinovirus (hRV) in 2 (4%), hPIV4-hRV co-infection in four (8%) and adenovirus or the OCR43/HKU-1 coronavirus in two (4%) cases; no IAV was detected. Virome sequencing allowed to reconstruct sequences of most PCR-identified rhinoviruses and hPIV-3/human respirovirus-3. Conclusions: COVID-19 was cause to a low proportion of symptomatic RTI among adults. Among COVID-negative participants, symptomatic RTI was predominantly associated with hPIV and hRV. Therefore, respiratory viruses other than SARS-CoV-2 should be considered in the clinical management and prevention of adult RTI in the post-pandemic era.

Evaluation of a Live-Attenuated Human Parainfluenza Virus Type 2 Vaccine in Adults and Children.

We conducted a phase I clinical trial of the live-attenuated recombinant human parainfluenza virus type 2 (HPIV2) vaccine candidate rHPIV2-15C/948L/∆1724 sequentially in adults, HPIV2-seropositive children, and HPIV2-seronegative children, the target population for vaccination. rHPIV2-15C/948L/∆1724 was appropriately restricted in replication in adults and HPIV2-seropositive children but was overattenuated for HPIV2-seronegative children.

In Vitro Potential Virucidal Effect Evaluation of Xibornol on Human Adenovirus Type 5, Human Rhinovirus Type 13, Human Coronavirus 229E, Human Parainfluenza Virus Type 1, and Human Respiratory Syncytial Virus.

The availability of virucidal compounds to reduce the impact of respiratory viruses is a relevant topic for public health, especially during the recent coronavirus disease (COVID-19) pandemic. Antimicrobial properties of Xibornol are known since the 1970s, but its activity on viruses is currently little explored. In this study, Xibornol activity at a fixed concentration of 0.03 mg/100 ml has been evaluated on five respiratory viruses (Human Adenovirus 5, Human Rhinovirus type 13, Human Coronavirus 229E, Human Parainfluenza Virus type 1, and Human Respiratory Syncytial Virus) through in vitro experiments based on adapted European standard UNI EN 14476-20019. The experiments were carried out under two different environmental conditions, one with the addition of fetal bovine serum to simulate an in vivo condition (dirty condition) and the other without the addition of any organic substances (clean condition). The viral abatement of Xibornol (expressed as Log10 reduction - LR) was statistically significant under both clean and dirty environmental conditions. Namely, in clean condition, LR ranged from 2.67 to 3.84, while in the dirty one the abatement was slightly lower (from 1.75 to 3.03). Parainfluenza Virus and Human Adenovirus were most resistant compared to the other viruses. The obtained data confirmed Xibornol activity and its use as topic substance for viral inactivation to prevent upper respiratory tract disease.

Recent increase in the detection of human parainfluenza virus during the coronavirus disease-2019 pandemic in the Republic of Korea.

BACKGROUND: Since the onset of the coronavirus disease-2019 (COVID-19) pandemic, the prevalence of respiratory infectious diseases, particularly, the flu epidemic, has considerably decreased. The low detection rate and decreased number of specimens have hindered the implementation of the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS), a sentinel surveillance system. Most patients with influenza-like illness visit the COVID-19 screening clinic; therefore, the number of samples collected in sentinel surveillance has decreased by more than 50%. Thus, the Korea Disease Control and Prevention Agency supplemented sentinel surveillance with non-sentinel surveillance by private medical diagnostic centers. We report here a delayed and unprecedented high detection of human parainfluenza virus (hPIV) in the Republic of Korea during the COVID-19 pandemic through sentinel and non-sentinel surveillance. We also examined the causes and implications of the changes in prevalence of hPIV.l METHODS: We collected data for 56,984 and 257,217 samples obtained through sentinel and non-sentinel surveillance, respectively. Eight viruses were confirmed using real-time reverse transcription-polymerase chain reaction (PCR) or real-time PCR. Some specimens from the sentinel surveillance were used for genetic characterization of hPIV type 3. RESULTS: In 2020, hPIV was rarely detected; however, it was detected in August 2021. The detection rate continued to increase considerably in September and reached over 70% in October, 2021. The detection rate of hPIV3 was significantly higher in infants and preschoolers aged 0-6 years in both sentinel and non-sentinel surveillance. Detection of hPIV was delayed in metropolitan areas compared to that in suburban regions. The hemagglutinin-neuraminidase sequences of hPIV3 generated in 2021 were not distinct from those detected prior to the COVID-19 pandemic. CONCLUSIONS: The operation of non-sentinel and sentinel surveillance to monitor respiratory viruses could sensitively detect an unprecedented revival of hPIV in the Republic of Korea during the COVID-19 pandemic.

Characterization of Human Parainfluenza Virus Receptor Using Terminal Sialic Acid Linkage-Modified Cells.

Human parainfluenza virus type 1 (hPIV1) and type 3 (hPIV3) are respiratory pathogen viruses that bind to terminal sialic acids of glycoconjugates on the cell surface hemagglutinin-neuraminidase glycoprotein. Sialic acid residues are linked to the galactose residue primarily by α2,3 or α2,6 linkages on the terminal of glycoprotein or glycolipids. One of the major determinants of pathogenicity or tissue tropism is virus binding or infection specificity for each sialyl linkage. Sialic linkage-modified human blood cells or mammalian cells that mainly have α2,3- or α2,6-linked sialic acid residues on the surface can be prepared by treatment with linkage-specific sialidases or sialyltransferases. These linkage-modified cells can be used in hemagglutination assays to estimate virus particles' binding specificity, hemadsorption assays to estimate virus glycoproteins' binding specificity, and virus infectivity assays. These methods contribute to identifying the specificity of sialic acid lineage recognition of the hPIV or other sialic acid-binding viruses.

Seasonal epidemiological and clinical characteristics of pediatric patients with human parainfluenza virus infection by serotype: a retrospective study.

BACKGROUND: The development of the polymerase chain reaction (PCR) test promoted the evaluation of the epidemiological and clinical characteristics of human parainfluenza virus (HPIV) type 4, which has been rarely studied using conventional diagnostic methods. This study aimed to determine the seasonal epidemiological and clinical characteristics of all four HPIV serotypes (HPIV-1, HPIV-2, HPIV-3, and HPIV-4) during the era of PCR testing. METHODS: The medical records of hospitalized pediatric patients diagnosed with HPIV infections by a multiplex PCR test between 2015 and 2021 were retrospectively reviewed to determine the seasonal distributions of each HPIV serotype. For patients with a single HPIV infection, the clinical characteristics of each HPIV serotype were evaluated and compared with one another. RESULTS: Among the 514 cases of HPIV infection, HPIV-1, HPIV-2, HPIV-3, and HPIV-4 were identified in 27.2%, 11.9%, 42.6%, and 18.3% of cases, respectively. HPIV-3 was most prevalent in spring, and the other three serotypes were most prevalent in autumn. For patients with a single HPIV infection, those infected by HPIV-1 and HPIV-3 were younger than those infected by HPIV-2 and HPIV-4 (P < 0.001). Croup and lower respiratory tract infection (LRI) were most frequently diagnosed in patients infected by HPIV-1 (P < 0.001) and HPIV-4 (P = 0.002), respectively. During 2020-2021, HPIV-3 was most prevalent in autumn and caused fewer LRIs (P = 0.009) and more seizures (P < 0.001) than during 2015-2019. CONCLUSIONS: Each HPIV serotype exhibited a distinct seasonal predominance, and some differences in the clinical characteristics of the HPIV serotypes were observed. HPIV-4 acted as an important cause of LRI. Considering the recent changes in the epidemiological and clinical characteristics of HPIV-3, more time-series analyses should be conducted.

Epicatechin analogues may hinder human parainfluenza virus infection by inhibition of hemagglutinin neuraminidase protein and prevention of cellular entry.

Human parainfluenza viruses (HPIVs) are ( -)ssRNA viruses belonging to Paramyoviridaie family. They are one of the leading causes of mortality in infants and young children and can cause ailments like croup, bronchitis, and pneumonia. Currently, no antiviral medications or vaccines are available to effectively treat parainfluenza. This necessitates the search for a novel and effective treatment. Computer-aided drug design (CADD) methodology can be utilized to discover target-based inhibitors with high accuracy in less time. A library of 45 phytocompounds with immunomodulatory properties was prepared. Thereafter, molecular docking studies were conducted to characterize the binding behavior of ligand in the binding pocket of HPIV3 HN protein. The physicochemical properties for screened compounds were computed, and the top hits from docking studies were further analyzed and validated using molecular dynamics simulation studies using the Desmond module of Schrodinger Suite 2021-1, followed by MM/GBSA analysis. The compounds CID:72276 (1) and CID:107905 (2) emerged as lead compounds of our in silico investigation. Further in vitro studies will be required to prove the efficacy of lead compounds as inhibitors and to determine the exact mechanism of their inhibition. Computational studies predict three natural flavonoids to inhibit the HN protein of HPIV3.

Human parainfluenza 2 & 4: Clinical and genetic epidemiology in the UK, 2013-2017, reveals distinct disease features and co-circulating genomic subtypes.

BACKGROUND: Human Parainfluenza viruses (HPIV) comprise of four members of the genetically distinct genera of Respirovirus (HPIV1&3) and Orthorubulavirus (HPIV2&4), causing significant upper and lower respiratory tract infections worldwide, particularly in children. However, despite frequent molecular diagnosis, they are frequently considered collectively or with HPIV4 overlooked entirely. We therefore investigated clinical and viral epidemiological distinctions of the relatively less prevalent Orthorubulaviruses HPIV2&4 at a regional UK hospital across four autumn/winter epidemic seasons. METHODS: A retrospective audit of clinical features of all HPIV2 or HPIV4 RT-PCR-positive patients, diagnosed between 1st September 2013 and 12th April 2017 was undertaken, alongside sequencing of viral genome fragments in a representative subset of samples. RESULTS: Infection was observed across all age groups, but predominantly in children under nine and adults over 40, with almost twice as many HPIV4 as HPIV2 cases. Fever, abnormal haematology, elevated C-reactive protein and hospital admission were more frequently seen in HPIV2 than HPIV4 infection. Each of the four seasonal peaks of either HPIV2, HPIV4 or both, closely matched that of RSV, occurring in November and December and preceding that of Influenza A. A subset of viruses were partially sequenced, indicating co-circulation of multiple subtypes of both HPIV2&4, but with little variation between each epidemic season or from limited global reference sequences. CONCLUSIONS: Despite being closest known genetic relatives, our data indicates a potential difference in associated disease between HPIV2 and HPIV4, with more hospitalisation seen in HPIV2 mono-infected individuals, but a greater overall number of HPIV4 cases.

Liver Enzyme Elevation Related to Human Parainfluenza Virus Type 3 Infection.

The human parainfluenza viruses are common causes of upper and lower respiratory tract infection; however, nonrespiratory infections with human parainfluenza viruses are rare, and there are no reports of pediatric cases of liver enzyme elevation. We present 2 pediatric patients who developed liver enzyme elevation related to human parainfluenza virus type 3 infection.

Novel Vaccines and Drugs That Target the Surface Glycoproteins of Influenza Viruses, RSV, Parainfluenza Viruses, and SARS-CoV-2.

Newly emerging and seasonal respiratory viruses have a great impact on public health[...]

Respiratory viruses among pediatric inpatients with acute lower respiratory tract infections in Jinan, China, 2016-2019.

The viral etiologies responsible for acute lower respiratory tract infections (ALRI) are a major cause of pediatric hospitalization, and some develop severe diseases requiring pediatric intensive care unit (PICU) admission. The aim of this study is to determine the prevalence of viruses and risk factors associated with PICU admission among patients hospitalized for ALRI. Nasopharyngeal swabs were collected to detect human rhinovirus (HRV), influenza A and B viruses (IAV and IBV), parainfluenza viruses (PIV), and respiratory syncytial virus (RSV) by reverse transcription-polymerase chain reaction (PCR) and adenovirus (ADV) by PCR. Of the 5590 pediatric inpatients enrolled, respiratory viral infection occurred in 2102 (37.60%) patients, including 1846 (33.02%) single and 256 (4.58%) mixed viral infections. Among the nasopharyngeal swabs from pediatric inpatients, HRV accounted for the highest detection rate (16.48%), followed by PIV (8.35%), RSV (7.41%), ADV (4.63%), IAV (3.51%), and IBV (2.08%). The positive rate of viral tests decreased with increasing age and was higher in males (39.29%) than females (34.67%). The prevalence of viral infection was the highest in winter (41.57%) and lowest in autumn (31.78%). Each virus had a seasonal pattern, with peaks occurring in months of their epidemic seasons. RSV infection and the presence of comorbidities including congenital tracheal stenosis, congenital heart disease, metabolic disorder, immunodeficiency, renal disease, gastrointestinal disease, and neurological disorder might be associated with the need for PICU admission. Therefore, this study provides useful information for the prevention and control of virus-related respiratory diseases and the early identification of and intervention in severe cases.