Respiratory Virus Research Articles

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Antigenicity, epitope mapping, and intracellular distribution of the NSP7α protein of porcine reproductive and respiratory syndrome virus

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that causes huge economic losses to the global pig industry. Nonstructural protein 7α (NSP7α) of PRRSV is highly conserved among different lineages of PRRSV and could be a potential target for the development of detection methods. In this study, NSP7α was expressed in prokaryote (Escherichia coli) and purified. An NSP7α-ab-ELISA detection method was established, the NSP7α-ab-ELISA has 93.1 % coincidence rate with IDEXX PRRS X3 ab test kit. NSP7α antibody was detected in pig serum by ELISA 14 days following PRRSV infection. Three monoclonal antibodies (4H9, 3F2, and C10) against NSP7α prepared by a hybridoma technique were used for epitope mapping by indirect immunofluorescence. The 4H9, 3F2, and C10 antibodies all recognized the C-terminal 72–149 amino acid region of NSP7α. 4H9 reacted with amino acids 135–143, but 3F2 and C10 did not react with any truncated polypeptide. In addition, by using the monoclonal antibodies, NSP7α was localized solely in the cytoplasm, while the N protein was distributed in the cytoplasm and nucleus. The collective findings of the antigenicity and epitope of NSP7α will be helpful for understanding the antigenicity of NSP7α and developing PRRSV diagnostic methods.

COVID-19, Influenza, and RSV in Children and Adults: A Clinical Comparative Study of 12,000 Cases.

(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5-2.4] in children and 21.4 times [2.4-189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs.

SARS-CoV-2 pandemic non-pharmacologic interventions temporally associated with reduced pediatric infections due to Mycoplasma pneumoniae and co-infecting respiratory viruses in Arkansas.

Non-pharmacologic interventions (NPIs) effectively curtailed the spread of SARS-CoV-2 and, fortuitously, many other aerosol-transmitted respiratory pathogens. This study included the largest data set of symptomatic, pediatric patients from within the United States spanning a period from November 2017 through December 2023, and encompassed individuals residing in both rural and urban settings. We observed a strong correlation between the implementation and cessation of NPIs with the rate of respiratory infections due to Mycoplasma pneumoniae and viral co-infections. These infections are returning to baseline levels approximately 2 years following NPI cessation. This observation was not unexpected since the replication time for viruses is exponentially faster than that of bacteria. The resurgence of M. pneumoniae and likely other atypical bacterial pathogens is currently in process. Healthcare providers should strongly consider these pathogens in individuals presenting with respiratory tract illnesses.

Virucidal activity of a plant-oil-based oral rinse against respiratory viruses

Respiratory viruses have been reported to infect the salivary glands and the throat, which are potential reservoirs for virus replication and transmission. Therefore, strategies to reduce the amount of infective virus particles in the oral mucous membranes could lower the risk of transmission. In this study, the viral inactivation capacity of a plant oil-based oral rinse (Salviathymol) was evaluated in comparison to chlorhexidine (Chlorhexamed FORTE) using a quantitative suspension test according to EN 14476. Salviathymol efficiently inactivated severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), respiratory syncytial virus (RSV) and two influenza strains to undetectable levels, highlighting its potential as preventive measure to lower transmission of respiratory viruses.

Caffeic acid phenethyl ester: an effective antiviral agent against porcine reproductive and Respiratory Syndrome Virus

Porcine Reproductive and Respiratory Syndrome (PRRS) presents a formidable viral challenge in swine husbandry. Confronting the constraints of existing veterinary pharmaceuticals and vaccines, this investigation centers on Caffeic Acid Phenethyl Ester (CAPE) as a prospective clinical suppressant for the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). The study adopts an integrated methodology to evaluate CAPE's antiviral attributes. This encompasses a dual-phase analysis of CAPE's interaction with PRRSV, both in vitro and in vivo, and an examination of its influence on viral replication. Varied dosages of CAPE were subjected to empirical testing in animal models to quantify its efficacy in combating PRRSV infections. The findings reveal a pronounced antiviral potency, notably in prophylactic scenarios. As a predominant component of propolis, CAPE stands out as a promising candidate for clinical suppression, showing exceptional effectiveness in pre-exposure prophylaxis regimes. This highlights the potential of CAPE in spearheading cutting-edge strategies for the management of future PRRSV outbreaks.

ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells.

The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the enzymatic activity of TMPRSS2 in a non-catalytic manner. Furthermore, we demonstrate that ACE2 knockdown inhibits TMPRSS2-mediated cleavage of IAV hemagglutinin (HA) in Calu-3 human airway cells and suppresses virus titers 100- to 1.000-fold. Transient expression of ACE2 in ACE2-deficient cells increased TMPRSS2-mediated HA cleavage and IAV replication. ACE2 knockdown also reduced titers of MERS-CoV and prevented S cleavage by TMPRSS2 in Calu-3 cells. By contrast, proteolytic activation and multicycle replication of IAV with multibasic HA cleavage site typically cleaved by furin were not affected by ACE2 knockdown. Co-immunoprecipitation analysis revealed that ACE2-TMPRSS2 interaction requires the enzymatic activity of TMPRSS2 and the carboxypeptidase domain of ACE2. Together, our data identify ACE2 as a new co-factor or stabilizer of TMPRSS2 activity and as a novel host cell factor involved in proteolytic activation and spread of IAV in human airway cells. Furthermore, our data indicate that ACE2 is involved in the TMPRSS2-catalyzed activation of additional respiratory viruses including MERS-CoV.IMPORTANCEProteolytic cleavage of viral envelope proteins by host cell proteases is essential for the infectivity of many viruses and relevant proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of several respiratory viruses, including influenza A virus. TMPRSS2 was previously shown to interact with angiotensin-converting enzyme 2 (ACE2). Here, we report the mechanistic details of this interaction. We demonstrate that ACE2 increases or stabilizes the enzymatic activity of TMPRSS2. Furthermore, we describe ACE2 involvement in TMPRSS2-catalyzed cleavage of the influenza A virus hemagglutinin and MERS-CoV spike protein in human airway cells. These findings expand our knowledge of the activation of respiratory viruses by TMPRSS2 and the host cell factors involved. In addition, our results could help to elucidate a physiological role for TMPRSS2.

A Low-cost High-throughput Targeted Sequencing for the Accurate Detection of Respiratory Tract Pathogen

Introduction: The current gold standard for SARS-CoV-2 diagnosis by real-time RT-PCR has limitations of gene numbers that can be detected. In this study, we developed a low-cost and high-throughput next-generation sequencing technology that can overcome the limitations of RT-PCR. Methodology: A targeted sequencing panel (TSP) consisting of approximately 500 amplicons was designed that can simultaneously detect a broad range of gene loci of SARS-CoV-2 and genes for the most common viruses of respiratory infectious viruses in a single run of up to 96 samples. 448 samples and 31 control samples were examined independently with both TSP and RT-PCR, results were compared for accuracy and other indicators. Results: TSP identified 50 SARS-CoV-2 positive samples with a 99.33% match to RT-PCR results. It is not surprising that TSP also identified multiple viral infections from 96 samples, whereas RT-PCR could not. TSP demonstrated its ability to conclude diagnosis for those undecided from RT-PCR tests. Conclusion: Our data demonstrated that TSP is a fast and accurate test for detecting multiple pathogen infections of the respiratory tract.

Unveiling Shared Immune Responses in Porcine Alveolar Macrophages during ASFV and PRRSV Infection Using Single-Cell RNA-seq.

African swine fever virus (ASFV) and porcine reproductive and respiratory syndrome virus (PRRSV) infections lead to severe respiratory diseases in pigs, resulting in significant economic losses for the global swine industry. While numerous studies have focused on specific gene functions or pathway activities during infection, an investigation of shared immune responses in porcine alveolar macrophages (PAMs) after ASFV and PRRSV infections was lacking. In this study, we conducted a comparison using two single-cell transcriptomic datasets generated from PAMs under ASFV and PRRSV infection. Pattern recognition receptors (PRRs) RIG-I (DDX58), MDA5 (IFIH1), and LGP2 (DHX58) were identified as particularly recognizing ASFV and PRRSV, triggering cellular defense responses, including the upregulation of four cytokine families (CCL, CXCL, IL, and TNF) and the induction of pyroptosis. Through weighted gene co-expression network analysis and protein-protein interaction analysis, we identified thirteen gene and protein interactions shared by both scRNA-seq analyses, suggesting the ability to inhibit both ASFV and PRRSV viral replication. We discovered six proteins (PARP12, PARP14, HERC5, DDX60, RSAD2, and MNDA) in PAMs as inhibitors of ASFV and PRRSV replication. Collectively, our findings showed detailed characterizations of the immune responses in PAMs during ASFV and PRRSV infections, which may facilitate the treatments of these viral diseases.

Dual-Modal Colorimetric and Surface-Enhanced Raman Scattering (SERS)-Based Lateral Flow Immunoassay for Ultrasensitive Detection of SARS-CoV-2 Using a Plasmonic Gold Nanocrown.

The 2019 coronavirus disease (COVID-19) outbreak created an unprecedented need for rapid, sensitive, and cost-effective point-of-care diagnostic tests to prevent and mitigate the spread of the SARS-CoV-2 virus. Herein, we demonstrated an advanced lateral flow immunoassay (LFIA) platform with dual-functional [colorimetric and surface-enhanced Raman scattering (SERS)] detection of the spike 1 (S1) protein of SARS-CoV-2. The nanosensor was integrated with a specially designed core-gap-shell morphology consisting of a gold shell decorated with external nanospheres, a structure referred to as gold nanocrown (GNC), labeled with a Raman reporter molecule 1,3,3,1',3',3'-hexamethyl-2,2'-indotricarbocyanine iodide (HITC) to produce a strong colorimetric signal as well as an enhanced SERS signal. Among the different plasmonics-active GNC nanostructures, the GNC-2 morphology, which has a shell decorated with an optimum number and size of nanospheres, produces an intense dark-blue colorimetric signal and ultrahigh SERS signal. The limit of detection (LOD) of the S1 protein via colorimetric detection LFIA was determined to be 91.24 pg/mL. On the other hand, the LOD for the SERS LFIA method was more than three orders of magnitude lower at 57.21 fg/mL. Furthermore, we analyzed the performance of the GNC-2 nanosensor for directly analyzing the S1 protein spiked in saliva samples without any sample pretreatment and achieving the LOD as low as 39.65 fg/mL using SERS-based plasmonics-enhanced LFIA, indicating ultrahigh detection sensitivity. Overall, our GNC nanosensor showed excellent sensitivity, reproducibility, and rapid detection of the SARS-CoV-2 S1 protein, demonstrating excellent potential as a promising point-of-care platform for the early detection of respiratory virus infections.

Vaccines against respiratory syncytial virus

Respiratory syncytial virus (RSV is) a common respiratory virus responsible for considerable morbidity and mortality among infants, elderly with comorbidity, and immunocompromised adults. Two vaccines, Abrysvo and Arexvy, have been approved for prevention of severe RSV infection in adults ≥ 60 years of age. In addition, Abrysvo is approved for use during pregnancy to protect infants from RSV-associated lower respiratory tract infection. Currently, there is no national recommendation for the use of the vaccines, but vaccination of elderly at highest risk of severe RSV infection should be considered in a shared clinical decision making.

Research Progress on the NSP10 Protein of Porcine Reproductive and Respiratory Syndrome Virus.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and pathogenic infectious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It manifests as reproductive disorders in sows and respiratory disorders in piglets. PRRSV infects swine herds with symptoms such as abortions, stillbirths, and mummified fetuses in gestating sows. Piglets mainly experience abdominal respiration and respiratory symptoms. To date, the prevention of PRRS relies primarily on vaccination and the implementation of various preventive and control measures. Swine deaths caused by PRRS have resulted in significant economic losses to the pig industry worldwide. Non-structural protein 10 (NSP10) has helicase and adenosine triphosphatase (ATPase) activities that unwind DNA and RNA and play important roles in viral replication and transcription. Hence, it can be potentially used to develop novel reagents for the detection of PPRSV. This article reviews genetic variations, interaction with viral and host proteins, effects on PRRSV replication, immunomodulation, apoptosis, and viral virulence of NSP10, with the aim of providing a theoretical basis for the prevention and control of PRRS and drug development in the future.

SQSTM1 downregulates avian metapneumovirus subgroup C replication via mediating selective autophagic degradation of viral M2-2 protein.

Avian metapneumovirus subgroup C (aMPV/C), an important pathogen causing acute respiratory infection in chickens and turkeys, contributes to substantial economic losses in the poultry industry worldwide. aMPV/C has been reported to induce autophagy, which is beneficial to virus replication. Sequestosome 1 (SQSTM1/P62), a selective autophagic receptor, plays a crucial role in viral replication by clearing ubiquitinated proteins. However, the relationship between SQSTM1-mediated selective autophagy and aMPV/C replication is unclear. In this study, we found that the expression of SQSTM1 negatively regulates aMPV/C replication by reducing viral protein expression and viral titers. Further studies revealed that the interaction between SQSTM1 and aMPV/C M2-2 protein is mediated via the Phox and Bem1 (PB1) domain of the former, which recognizes a ubiquitinated lysine at position 67 of the M2-2 protein, and finally degrades M2-2 via SQSTM1-mediated selective autophagy. Collectively, our results reveal that SQSTM1 degrades M2-2 via a process of selective autophagy to suppress aMPV/C replication, thereby providing novel insights for the prevention and control of aMPV/C infection.IMPORTANCEThe selective autophagy plays an important role in virus replication. As an emerging pathogen of avian respiratory virus, clarification of the effect of SQSTM1, a selective autophagic receptor, on aMPV/C replication in host cells enables us to better understand the viral pathogenesis. Previous study showed that aMPV/C infection reduced the SQSTM1 expression accompanied by virus proliferation, but the specific regulatory mechanism between them was still unclear. In this study, we demonstrated for the first time that SQSTM1 recognizes the 67th amino acid of M2-2 protein by the interaction between them, followed by M2-2 degradation via the SQSTM1-mediated selective autophagy, and finally inhibits aMPV/C replication. This information supplies the mechanism by which SQSTM1 negatively regulates viral replication, and provides new insights for preventing and controlling aMPV/C infection.

The burden of RSV, hMPV, and PIV amongst hospitalized adults in the United States from 2016 to 2019.

Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus (PIV) hospitalize many people yearly. Though severe lower respiratory tract disease has been described in children, the elderly, and the immunocompromised, there is a gap in our understanding of RSV, hMPV, and PIV in hospitalized adults. We sought to evaluate the association of RSV, hMPV, and PIV with severe respiratory disease requiring noninvasive or mechanical ventilation and death in hospitalized adults in the United States. We conducted a retrospective, pooled, cross-sectional study of general medicine hospitalizations in the United States from 2016 to 2019 using the National Inpatient Sample published by the Agency for Healthcare Quality and Research. We used multivariable Poisson regression to estimate the likelihood of severe respiratory disease or death. We used linear regression to estimate the mean difference in length of stay for those hospitalized with and without a respiratory virus. We found that RSV (incidence rate ratio [IRR]: 1.68, 95% confidence interval [CI]: 1.61-1.74, p < .001), hMPV (IRR: 1.82, 95% CI: 1.71-1.93, p < .001), and PIV (IRR: 1.81, 95% CI: 1.68-1.94, p < .001) were independently associated with severe respiratory disease, even after adjustment. Additionally, we found the presence of a respiratory virus prolonged hospitalizations by (0.79 ± 0.27 days, p < .003) for RSV, (0.88 ± 0.28 days, p < .002) for hMPV, and (1.43 ± 0.30 days, p < .001) for PIV. RSV, hMPV, and PIV have a significant burden on hospitalized adults, even without classic risk factors.

Respiratory tract viral infections associated sepsis in patients with underlying liver disease: Viral sepsis an entity to look forward!

Sepsis remains a global health burden associated with significant morbidity and mortality. Bacteria are known to be the predominant pathogens in sepsis; however, viral etiologies in sepsis are still under diagnosed. Respiratory viral pathogens have been previously linked to sepsis, but the knowledge of incidence, disease burden and mortality of viral-induced sepsis remains limited. This study aimed at understanding the role of respiratory viral infections in the causation of sepsis in liver disease patients. In this retrospective study, the clinical records of liver disease patients with influenza-like illness, whose requests for respiratory viral testing were received from January 2019 to December 2022, were reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics,Utah, USA). Of 1391 patients tested, a respiratory viral etiology was detected in 23%. The occurrence of sepsis was seen in 35%. Among these, isolated viral etiology with no other bacterial/fungal coinfection was found in 55% of patients. Rhinovirus/Enterovirus was found as the most common underlying viral etiology (23.4%). The sepsis prevalence was higher among patients with associated comorbidities (45%) and decompensated cirrhosis (84%). On multi-variable analysis, no factor was found independently associated with sepsis-related mortality. This study underlines the importance of isolated viral etiology in causation of sepsis among liver disease patients. Patients with comorbidities, older age and decompensated cirrhosis are at an increased risk of developing sepsis and are associated with poorer outcomes. Accurate and timely identification of the viral etiology in sepsis would prevent the misuse of antibiotics and improve overall patient care.

Intranasal Epitope-Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus.

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366 , a nucleoprotein-derived epitope and PA224 , a polymerase acidic subunit derived epitope, are bioengineered. These BP-NP366 /PA224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient-temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP-NP366 /PA224 without adjuvant triggers influenza-specific CD8+ T cell priming and memory CD8+ T cell development. Co-delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza-specific pulmonary resident memory CD8+ T cell pool. Intranasal, but not intramuscular delivery of BP-NP366 /PA224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.

Infection Risk Prediction in Healthcare Settings: Lessons from COVID-19 Contact Tracing.

Contact tracing aids epidemic control by enabling early detection and isolation without overburdening healthcare systems despite potential challenges. This study aimed to evaluate the practical application of contact and risk assessment-based models in predicting SARS-CoV-2 infection following exposure among healthcare workers in a large tertiary public university hospital in Türkiye. The study was designed as a retrospective cohort study, including contact tracing data from 3389 exposed healthcare workers from March 23, 2020, to October 22, 2021. Contact-based (mask use, contact duration and distance) and exposure risk-assessment-based (low, medium, high-risk) models with and without having symptoms were generated using logistic regression. SARS-CoV-2 infection was defined as having a positive SARS-CoV-2 RT-PCR test result. Adjustments were made to the models for demographic and occupational variables, previous infection, and vaccination. Model parameters were compared. Of 3389 exposed healthcare workers, 2451 underwent RT-PCR testing. Among those tested, RT-PCR positivity was 5.9% (144/2451). Lack of personal protective equipment use (odds ratio [OR]=1.64, 95% confidence interval [CI]=1.03-2.66) and ≥15 minutes of contact duration (1.89, 1.21-3.09) were significantly associated with RT-PCR positivity. In the risk-assessment model, being a high-risk contact increased the odds of RT-PCR positivity (OR=2.76, 95% CI=1.61-5.03). Adding the presence of symptoms to contact-based and risk assessment models improved model parameters (Akaike information criterion [AIC]: from 1086.1 to 1083.1; Tjur's R2: from 0.016 to 0.019, respectively). The inclusion of being symptomatic improved the contact-based and risk assessment-based models. Institutions should be encouraged to incorporate symptom inquiries into risk assessment protocols in response to newly emerging respiratory virus epidemics. Institutions lacking the capacity for extensive contact tracing are recommended, at minimum, to track symptomatic exposed workers for epidemic control.

Regulation of a Metabolic Gene Signature in Response to Respiratory Viruses and Type I Interferon Signaling

Respiratory viruses are the causative agents responsible for seasonal epidemics and occasional pandemic outbreaks and are a leading cause of death worldwide. Type I interferon (IFNα/β) signaling in the lung epithelial cells plays a major role in the innate immunity to respiratory viruses. Gene signatures are a set of differentially expressed genes in a particular disease or condition and are used to diagnose, monitor, and predict disease progression. These signatures can be used to identify regulatory modules and gene regulatory networks (GRNs) in mammalian signal transduction pathways. Considerable progress has been made in the identification of type I interferon-regulated gene signatures in the host response to respiratory viruses, including antiviral, immunomodulatory, apoptosis, and transcription factor signatures. Respiratory virus infections and host defenses require a dramatic change in the metabolic flux of macromolecules involved in nucleotide, lipid, and protein metabolism. The profiling of IFN-stimulated metabolic genes induced in the host response to several respiratory viruses led to the identification of a common gene signature in human lung epithelial cells and in the lungs of mouse models of respiratory virus infection. The regulation of the metabolic gene signature was correlated with the induction of IFN-beta (IFN-β) and IFN-inducible transcription factors at the RNA level in lung epithelial cells. Furthermore, the gene signature was also detected in response to bacterial lipopolysaccharide-induced acute lung injury. A protein interaction network analysis revealed that metabolic enzymes interact with IFN-regulated transcription factors and members of the unfolded protein response (UPR) to form a module and potentially regulate type I interferon signaling, constituting a feedback loop. In addition, components of the metabolic gene expression signature were differentially regulated in the lung tissues of COVID-19 patients compared with healthy controls. These results suggest that the metabolic gene signature is a potential therapeutic target for the treatment of respiratory virus infections and inflammatory diseases.

Severe Pneumonia Caused by Respiratory Syncytial Virus and Adenovirus in Children from 2 to 24 Months at Children's Hospital 1 in Ho Chi Minh City, Vietnam.

In Vietnam, due to the lack of facilities to detect respiratory viruses from patients' specimens, there are only a few studies on the detection of viral pathogens causing pneumonia in children, especially respiratory syncytial virus (RSV) and adenovirus (Adv). Here, we performed a cross-sectional descriptive prospective study on 138 children patients from 2 to 24 months old diagnosed with severe pneumonia hospitalized at the Respiratory Department of Children's Hospital 1 from November 2021 to August 2022. The number of patients selected in this study was based on the formula n = ([Z(1 - α/2)]2 × P [1 - P])/d2, with α = 0.05, p = 0.5, and d = 9%, and the sampling technique was convenient sampling until the sample size was met. A rapid test was used to detect RSV and Adv from the nasopharyngeal swabs and was conducted immediately after the patient's hospitalization. Laboratory tests were performed, medical history interviews were conducted, and nasotracheal aspirates were collected for multiplex real-time PCR (MPL-rPCR) to detect viral and bacterial pathogens. The results of the rapid test and the MPL-rPCR in the detection of both pathogens were the same at 31.9% (44/138) for RSV and 8.7% (7/138) for Adv, respectively. Using MPL-rPCR, the detection rate was 21% (29/138) for bacterial pathogens, 68.8% (95/138) for bacterial-viral co-infections, and 6.5% (9/138) for viral pathogens. The results showed few distinctive traits between RSV-associated and Adv-associated groups, and the Adv group children were more prone to bacterial infection than those in the RSV group. In addition, the Adv group experienced a longer duration of treatment and a higher frequency of re-hospitalizations compared to the RSV group. A total of 100% of Adv infections were co-infected with bacteria, while 81.82% of RSV co-infected with bacterial pathogens (p = 0.000009). This study might be one of the few conducted in Vietnam aimed at identifying viral pathogens causing severe pneumonia in children.

A Wash-Free Spheres-on-Sphere Strategy for On-Site and Multiplexed Biosensing.

Respiratory infections and food contaminants pose severe challenges to global health and the economy. A rapid on-site platform for the simultaneous detection of multiple pathogens is crucial for accurate diagnosis, appropriate treatment, and a reduced healthcare burden. Herein, we present a spheres-on-sphere (SOS) platform for multiplexed detection using a portable Coulter counter, which employs millimeter- and micron-sized spheres coupled with antibodies as multitarget probes. The assay allows for quantitative detection of multiple analytes within 20 min by simple mixing, enabling on-site detection. The platform shows high accuracy in identifying three respiratory viruses (SARS-CoV-2, influenza A virus, and parainfluenza virus) from throat swab samples, with LOD of 50.7, 32.4, and 49.1 pg/mL. It also demonstrates excellent performance in quantifying three mycotoxins (aflatoxin B1, deoxynivalenol, and ochratoxin A) from food samples. The SOS platform offers a rapid on-site approach with high sensitivity and specificity for applications in resource-limited settings.