Viral Respiratory Tract Research Articles

Investigation of the Effect of the COVID-19 Pandemic Period on Respiratory Tract Viruses at Istanbul Medical Faculty Hospital, Turkey.

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.

The Effect of Mask Use on Seasonal Virus Diversity in SARS CoV-2 Negative Patients Treated as Inpatients During the 2021-2022 and 2022-2023 Seasonal Flu Period.

The study aimed to explore the protective effect of mask use against respiratory tract viral agents during the pandemic. The study included patients with a COVID-19 negative test who were hospitalized in the pulmonary disease clinic with the diagnoses of asthma attack, chronic obstructive pulmonary disease (COPD) exacerbation, and pneumonia in two periods: during mandatory mask use (October 2021 - May 2022) and after the mask mandate was lifted (October 2022 - May 2023). Combined nose and throat swab samples taken from the patients were evaluated for viral agents by using the PCR test method. Viral agents isolated from the patients in the two periods were compared based on hospitalization diagnoses and periods. The study enrolled 1,335 patients, 483 female and 852 male. It was found that viral agents significantly increased during the period without a mask mandate compared to the period when the mask mandate was in effect (41.6% vs. 23.4%) (p < 0.001). During the period without mask mandate, influenza A, H1N1, and RSV/AB viruses significantly increased (p = 0.019, p = 0.003, p < 0.001, respectively). Our results indicated that mask use during the pandemic is protective against the transmission of respiratory tract viruses. Thus, it can be concluded that mask use is important not only in the coronavirus pandemic but also especially in influenza and RSV epidemics.

Do patients infected with human coronavirus before the COVID-19 pandemic have less risk of being infected with COVID-19?

Although seasonal human coronaviruses (HCoVs) have long been recognized as respiratory tract viruses, the newly identified SARS-CoV-2 caused a pandemic associated with severe respiratory failure. We aimed to evaluate the incidence of COVID-19 infection in patients diagnosed in three tertiary teaching hospitals, both with and without prior confirmed HCoV infection, and to compare these cohorts in terms of COVID-19 contraction. In our study, we examined HCoV PCR-positive cases obtained retrospectively between January 2014 and March 2020 from three University Hospital Microbiology Laboratories (Cohort 1), as well as PCR-negative patients detected in the same PCR cycle as the positive cases (Cohort 2). We also evaluated subgroups of HCoV-positive cases. There was no difference in COVID-19 contraction rates between Cohort 1 and Cohort 2 (p = 0.724). When previous HCoV subgroups of COVID-19-positive patients were examined, no significant difference was found between the betacoronavirus and alphacoronavirus subgroups (p = 0.822), among the four groups (NL63, 229E, OC43, HKU-1) (p = 0.207), or between the OC43 subgroup and the other groups (p = 0.295). Being previously infected with HCoV did not provide protection against COVID-19 in our study group. We suggest evaluating the possible effect of previous OC43 infection on COVID-19 contraction in larger cohorts.

Molecular Detection of Respiratory Tract Viruses in Chickens at the Point of Need by Loop-Mediated Isothermal Amplification (LAMP).

Accurate and timely molecular diagnosis of respiratory diseases in chickens is essential for implementing effective control measures, preventing the spread of diseases within poultry flocks, minimizing economic loss, and guarding food security. Traditional molecular diagnostic methods like polymerase chain reaction (PCR) require expensive equipment and trained personnel, limiting their use to centralized labs with a significant delay between sample collection and results. Loop-mediated isothermal amplification (LAMP) of nucleic acids offers an attractive alternative for detecting respiratory viruses in broiler chickens with sensitivity comparable to that of PCR. LAMP's main advantages over PCR are its constant incubation temperature (∼65 °C), high amplification efficiency, and contaminant tolerance, which reduce equipment complexity, cost, and power consumption and enable instrument-free tests. This review highlights effective LAMP methods and variants that have been developed for detecting respiratory viruses in chickens at the point of need.

Coinfection of viruses in children with community-acquired pneumonia

BackgroundVirus, particularly respiratory tract virus infection is likely to co-occur in children with community-acquired pneumonia (CAP). Study focusing on the association between common viruses coinfection and children with CAP is rare. We aimed to study the association between seven common viruses coinfection and clinical/laboratory indexes in children with CAP.MethodsSix hundred and eighty-four CAP cases from our hospital were enrolled retrospectively. Seven common viruses, including influenza A (FluA), influenza B (FluB), human parainfluenza virus (HPIV), Esptein-Barr virus (EBV), coxsackie virus (CoxsV), cytomegalovirus (CMV), and herpes simplex virus (HSV) were investigated for their associations with CAP. We analyzed the differences of hospitalization days, white blood cell (WBC), c-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), urine red blood cell (uRBC), blood urea nitrogen (BUN), serum creatinine (Scr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CKMB) among different viruses coinfection groups by using one-way ANOVA analysis. The differences of clinical/laboratory indexes between ordinary and severe pneumonia groups, as well as non-virus vs multi co-infection viruses groups, and single vs multi co-infection viruses groups by using independent samples T test. Receiver operating characteristic (ROC) curve analyses were applied to test the the predictive value of the clinical/laboratory parameters for the risk of viruses coinfections among CAP. Binary logistic analysis was performed to test the association between various indexes and viruses co-infection.ResultsEighty-four multiple viruses coinfections yielded different prognosis compared with that in 220 single virus coinfection. CMV coinfection was associated with longest hospitalization days, highest ALT, AST and CKMB level. HSV coinfection was associated with highest WBC count, CRP, ESR, and BUN. EBV coinfection was associated with highest PLT and PCT level. FluB coinfection was associated with highest Scr level. CoxsV coinfection was associated with highest uRBC, LDH and CK level. ROC curve analyses showed that CK had the largest area under the curve (AUC: 0.672, p < 10–4) for the risk of viruses coinfections risk in CAP. Significant association between PLT, uRBC, BUN, CK, and CKMB and virus coinfection risk in CAP was observed.ConclusionsMultiple viruses coinfections indicated different prognosis. Different viruses coinfection yielded varying degrees of effects on the cardiac, liver, kidney and inflamatory injury in CAP. The alterations of clinical/laboratory parameters, particularly CK may be associated with the risk of viruses coinfections in CAP.

Comparison of radiologic findings between SARS-CoV-2 and other respiratory tract viruses in critically ill children during the COVID-19 pandemic.

This study was planned because the radiological distinction of COVID-19 and respiratory viral panel (RVP)-positive cases is necessary to prioritize intensive care needs and ensure non-COVID-19 cases are not overlooked. With that purpose, the objective of this study was to compare radiologic findings between SARS-CoV-2 and other respiratory airway viruses in critically ill children with suspected COVID-19 disease. This study was conducted as a multicenter, retrospective, observational, and cohort study in 24 pediatric intensive care units between March 1 and May 31, 2020. SARS-CoV-2- or RVP polymerase chain reaction (PCR)-positive patients' chest X-ray and thoracic computed tomography (CT) findings were evaluated blindly by pediatric radiologists. We enrolled 225 patients in the study, 81 of whom tested positive for Coronovirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The median age of all patients was 24 (7-96) months, while it was 96 (17-156) months for COVID-19-positive patients and 17 (6-48) months for positive for other RVP factor (p < 0.001). Chest X-rays were more frequently evaluated as normal in patients with SARS-CoV-2 positive results (p = 0.020). Unilateral segmental or lobar consolidation was observed more frequently on chest X-rays in rhinovirus cases than in other groups (p = 0.038). CT imaging findings of bilateral peribronchial thickening and/or peribronchial opacity were more frequently observed in RVP-positive patients (p = 0.046). Chest X-ray and CT findings in COVID-19 patients are not specific and can be seen in other respiratory virus infections.

Infection and co-infection patterns of common upper respiratory tract viruses in patients with flu-like symptoms attending a fever clinic of a tertiary care hospital during the COVID-19 pandemic

Infection and co-infection patterns of common upper respiratory tract viruses in patients with flu-like symptoms attending a fever clinic of a tertiary care hospital during the COVID-19 pandemic

SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Different populations of A(H1N1)pdm09 viruses in a patient with hemolytic-uremic syndrome

Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized.A patient (age group 5–15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined.Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed.The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.

Effect of Face Masking on Transmission of SARS-CoV-2.

The efficacy of face masking for the public is not convincing to preventthe transmission of respiratory tract viruses such as SARS-CoV-2 when the criteria of evidence-based medicine are applied. This finding is mainly explained by the results from randomized-controlled trials (RCTs)when a high prevalence of the infection and a high compliance in mask wearingwas assured. Throughout these studies no significant protective effect was observed. Observational studies with surgical masks describe a significant protective effect, but are prone to confounders such as physical distance. Respirators do not provide an additional health benefit compared to surgical or medical masks (RCTs). Community masks can even increase the risk of infection (RCTs). Based on the categories of evidence-based medicine, the efficacy results can best be categorized as conflicting evidence. Many relevant adverse events are described when masks are worn for hours such as dyspnea (12.2-52.8%), headache (3.9-73.4%), pruritus (0.0-60.0%), and skin reactions (0.0-85.0%). Their frequency is often higher with respirators. In future pandemics, masks should only be recommended or mandated for settings in which a clinically relevant health benefitcan be expected, defined as theprevention of severe, critical or fatal disease, thatclearly outweighs the expectable associated adverse reactions.

SARS-CoV-2 Aerosol and Intranasal Exposure Models in Ferrets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the worldwide COVID-19 pandemic. Animal models are extremely helpful for testing vaccines and therapeutics and for dissecting the viral and host factors that contribute to disease severity and transmissibility. Here, we report the assessment and comparison of intranasal and small particle (~3 µm) aerosol SARS-CoV-2 exposure in ferrets. The primary endpoints for analysis were clinical signs of disease, recovery of the virus in the upper respiratory tract, and the severity of damage within the respiratory tract. This work demonstrated that ferrets were productively infected with SARS-CoV-2 following either intranasal or small particle aerosol exposure. SARS-CoV-2 infection of ferrets resulted in an asymptomatic disease course following either intranasal or small particle aerosol exposure, with no clinical signs, significant weight loss, or fever. In both aerosol and intranasal ferret models, SARS-CoV-2 replication, viral genomes, and viral antigens were detected within the upper respiratory tract, with little to no viral material detected in the lungs. The ferrets exhibited a specific IgG immune response to the SARS-CoV-2 full spike protein. Mild pathological findings included inflammation, necrosis, and edema within nasal turbinates, which correlated to positive immunohistochemical staining for the SARS-CoV-2 virus. Environmental sampling was performed following intranasal exposure of ferrets, and SARS-CoV-2 genomic material was detected on the feeders and nesting areas from days 2-10 post-exposure. We conclude that both intranasal and small particle aerosol ferret models displayed measurable parameters that could be utilized for future studies, including transmission studies and testing SARS-CoV-2 vaccines and therapeutics.

Retrospective analysis of respiratory virus infections in adults with hematologic malignancies.

The study aimed to evaluate respiratory virus infections in adult patients with hematological malignancies (HM). The medical records of patients who were followed up by the hematology clinic at Başakşehir Çam and Sakura City Hospital between March 2021 and March 2023 with a diagnosis of HM and who underwent real-time polymerase chain reaction (RT-PCR) testing for nasopharyngeal/oropharyngeal specimens taken with suspected respiratory tract infection constituted the study data. Infections were symptomatic in 64.56% of patients, and the most common symptoms were fever (48.10%) and cough (18.99%). The mortality rate was 25.32% over a two-year period. When the samples were examined, positive test frequency was 43.04%, and the three most common pathogens were Influenza A (10.13%), SARS-CoV-2 (8.86%), and rhinovirus/enterovirus (7.59%). The frequency of positive tests from HMs was highest in patients with AML (p=0.042). Respiratory PCR kit positivity was higher in patients who had any symptoms (p=0.002) and cough (p=0.003). Test positivity was higher in patients with any pathological radiological finding (p=0.039) and ground glass appearance (p=0.010). The risk of death was found to be 5.848 times higher in patients with dyspnea compared to those without (OR: 5.848, 95% CI: 1.143-29.915, p=0.034). Respiratory tract virus panel PCR test positivity is more common in patients with HM presenting with respiratory tract infection symptoms in the presence of AML diagnosis, symptomatic infection, cough, radiological findings, and ground glass appearance. Mortality risk is high in HM patients with respiratory tract virus infection who have shortness of breath.

Analysis of the common respiratory viruses in children with acute respiratory infection in a hospital in Lanzhou City from 2021 to 2022

To explore the situation of 8 common respiratory pathogens in children with acute respiratory infection (ARI) from 2021 to 2022.The retrospective study selected 8 710 ARI patients from September 2021 to August 2022 in the Maternal and Child Health Hospital of Gansu Province as the study object, patients aged 0 to 17 years old, including 5 048 male children and 3 662 female children. Indirect immunofluorescence was used to detect 8 common respiratory pathogens, including influenza virus A (FluA), influenza virus B (FluB), parainfluenza virus (PIV), respiratory syncytial virus (RSV), adenovirus (ADV), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), and Coxsackie virus group B (CoxB) IgM antibodies. χ2 test was used to analyze the results. The results showed that 1 497 of 8 710 children with ARI were positive, with a positive rate of 17.19%. The detection rate of MP among 8 common respiratory pathogens was 11.34%, accounting for 66.0%, followed by FluB, CoxB, PIV, RSV, ADV, FluA and CP, accounting for 13.83%, 9.55%, 6.01%, 2.61%, 1.47%, 0.40% and 0.13%, respectively. Respiratory tract viruses (FluA, FluB, RSV, ADV, PIV, CoxB) accounted for 33.86%.There were significant differences in the detection rates of PIV, ADV and MP among children of different genders (χ2=6.814, 5.154 and 17.784, P<0.05). The detection rate of school-age children (6-17 years old) was the highest, accounting for 33.27% (184/553). The detection rates of 8 common respiratory pathogens in patients with ARI were higher in spring and winter and lower in summer and autumn. To sum up, from 2021 to 2022, MP and FluB infection were dominant in ARI patients in our hospital. The peak period of 8 common respiratory pathogens was in spring and winter. The physical examination rate of 8 common respiratory pathogens in ARI patients aged 6-17 years old was the highest.

Viral Detection by Reverse Transcriptase Polymerase Chain Reaction in Upper Respiratory Tract and Metagenomic RNA Sequencing in Lower Respiratory Tract in Critically Ill Children With Suspected Lower Respiratory Tract Infection.

Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs). This is an analysis of of a seven-center prospective cohort study. Seven PICUs within academic children's hospitals in the United States. Critically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours. We evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement. Of 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001). Viral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.

Upper Respiratory Tract OC43 Infection Model for Investigating Airway Immune-Modifying Therapies.

Respiratory virus infections initiate and transmit from the upper respiratory tract (URT). Coronaviruses, including OC43, are a major cause of respiratory infection and disease. Failure to mount an effective antiviral immune response in the nasal mucosa increases the risk of severe disease and person-to-person transmission, highlighting the need for URT infection models to support the development of nasal treatments that improve coronavirus antiviral immunity. We aimed to determine if OC43 productively infected the mouse URT and would therefore be a suitable model to assess the efficacy and mechanism of action of nasal-targeting immune-modifying treatments. We administered OC43 via intranasal inoculation to wild-type Balb/c mice and assessed virus airway tropism (by comparing total respiratory tract vs. URT-only virus exposure) and characterized infection-induced immunity by quantifying specific antiviral cytokines and performing gene array assessment of immune genes. We then assessed the effect of immune-modulating therapies, including an immune-stimulating TLR2/6 agonist (INNA-X) and the immune-suppressing corticosteroid fluticasone propionate (FP). OC43 replicated in nasal respiratory epithelial cells, with peak viral RNA observed 2 days after infection. Prophylactic treatment with INNA-X accelerated expression of virus-induced IFN-λ and IFN-stimulated genes. In contrast, intranasal FP treatment increased nasal viral load by 2.4 fold and inhibited virus-induced IFN and IFN-stimulated gene expression. Prior INNA-X treatment reduced the immune-suppressive effect of FP. We demonstrate that the mouse nasal epithelium is permissive to OC43 infection and strengthen the evidence that TLR2 activation is a β-coronavirus innate immune determinant and therapeutic target.

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates.

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

Epidemiological and Clinical Characteristics of Human Parainfluenza Virus Infection in Children of Xianyang Children's Hospital in 2022

The incidence of HPIV infection in children is on the rise, particularly following the emergence of SARS-CoV-2, which presents a potential risk to the health of children.&#x0D; Objective: This study aims to investigate the epidemiological and clinical features of human parainfluenza virus (HPIV) in children admitted to Xianyang Children's Hospital (Xianyang Caihong Hospital) from January 2022 to December 2022.&#x0D; Methods: Out of the 5873 cases of hospitalised children, the ones which had HPIV as the only pathogen and were non-standard cases were excluded, and the rest were analysed for their clinical characteristics, based on the six nucleic acids kits used to detect HPIV in respiratory tract viruses. Results: Among 5873 cases of Nasopharyngeal swab specimens, there were 795 cases of HPIV antigen positive, of which 794 cases of HPIV3（13.52%, 3 cases of HPIV1（0.05%; There were 472 males (13.92%) and 325 females (13.09%) in them(χ2 =0.381, P=0.362).The infection rates in spring, summer, autumn and winter were 8.03%, 55.71%, 28.48% and 7.78%, respectively, and the difference of pairwise comparison were statistically significant (χ2=539.158, P=0).There were 318 cases (19.51%) in infant group and 164 cases (10.86%) in children group (χ2=45.118, P=0). With HPIV as the sole pathogen including 363 cases of bronchopneumonia, 237 cases of bronchitis, 8 cases of pertussis syndrome, 84 cases of bronchiolitis.&#x0D; Conclusion: ⑴. During the period of January to December 2022, Xianyang Children's Hospital has seen a high prevalence of HPIV, a virus causing lower respiratory tract infection, especially HPIV3. ⑵.No statistical evidence showed a difference between men and women in terms of high morbidity during spring and summer, which was more common among infants and young children. ⑶. Among children infected with HPIV, the four most common respiratory illnesses are bronchopneumonia, bronchitis, pertussis syndrome, and bronchiolitis. After undergoing symptomatic treatment, most children showed marked improvement. It is imperative to gain a thorough understanding of HPIV infections in children, enabling timely prevention and symptomatic treatment, identifying critical and serious illnesses, and reducing morbidity and mortality.

NEDD4 Regulated Pyroptosis Occurred from Co-infection between Influenza A Virus and Streptococcus pneumoniae.

Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and Streptococcus pneumoniae.

Computer-assisted identification of potential quinolone derivatives targeting Nipah virus glycoprotein attachment with human cell surface receptor ephrin-B2: Multistep virtual screening

Nipah Virus (NiV) is a single-stranded, negative-sense, highly lethal RNA virus. Even though NiV has close to 70–80% of mortality in India and Bangladesh, still there is no available US FDA-approved drug or vaccine. NiV attachment glycoprotein (NiV-G) is critical for NiV to invade the human cell where ephrinB2 which is a crucial membrane-bound ligand that acts as a target of NiV. Most of the research has been performed targeting NiV or human ephrin-B to date. Quinolone derivatives are proven scaffolds for many approved drugs used to treat various bacterial, viral respiratory tract, and urinary tract infections, and rheumatologic disorders such as systemic lupus erythematosus, rheumatoid arthritis. Therefore, we have tried to find potential drug molecules employing quinolone scaffold-based derivatives from PubChem targeting both NiV-G and ephrin-B2 protein. A total of 1500+ quinolone derivatives were obtained from PubChem which were screened based on Drug Likeness followed by being subjected to XP docking employing Schrödinger software. The top ten best molecules were then chosen for their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling based on the docking score ranking. Further, the top five molecules were selected for 200ns molecular dynamics (MD) simulation study with Desmond module followed by MM-GBSA study by Prime module of Schrödinger. The exhaustive analysis leads us to the top three probable lead drug molecules for NiV are PubChem CID 23646770, an analog of PubChem CID 67726448, and PubChem CID 10613168 which have predicted Ki values of 0.480 μm, 0.785 μm, and 0.380 μm, respectively. These proposed molecules can be the future drugs targeting NiV-G and human ephrin-B2 which requires further in vivo validation.

Impact of non-pharmaceutical interventions on circulating respiratory viruses during the COVID-19 pandemic in Turkey.

Non-pharmaceutical interventions (NPIs) applied to limit the SARS-CoV-2 pandemic also affect the circulation and seasonal characteristics of other respiratory viruses. Assess the impact of NPIs on the spread and seasonal characteristics of non-SARS-CoV-2 respiratory viruses and examine viral respiratory co-infections. Retrospective cohort SETTING: Single center in Turkey. Syndromic multiplex viral polymerase chain reaction (mPCR) panel results of patients admitted to the Ankara Bilkent City Hospital with symptoms of acute respiratory tract infection between April 1, 2020 and October 30, 2022 were evaluated. Two study periods before and after 1 July 2021, when the restrictions were discontinued, were statistically analyzed and compared to determine the effect of NPIs on circulating respiratory viruses. Prevalence of respiratory viruses as determined by syndromic mPCR panel. 11300 patient samples were evaluated. At least one respiratory tract virus was detected in 6250 (55.3%) patients. Of these, at least one respiratory virus was detected in 5% in the first period (between April 1, 2020 and June 30, 2021, when NPIs were applied), and in 95% in the second period (between July 1, 2021 and October 30, 2022, when NPIs were relaxed). After the removal of NPIs, there was a statistically significant increase in hRV/EV, RSV-A/B, Flu A/H3, hBoV, hMPV, PIV-1, PIV-4, hCoV-OC43, PIV-2 and hCoV-NL63 (P<.05). In the 2020-2021 season, when strict NPIs were applied, all respiratory viruses evaluated did not have the usual seasonal peak and there were no seasonal influenza epidemics during this period. NPIs resulted in a dramatic decrease in the prevalence of respiratory viruses and notable disruption of seasonal characteristics. Single-center study and retrospective. None.