Pathogenic Respiratory Virus Research Articles

Molecular characterization of human respiratory syncytial virus strains circulating among hospitalized children in Jordan

BackgroundHuman Respiratory Syncytial Virus (HRSV) is a primary cause of severe pediatric respiratory infections, particularly in infants and young children, often resulting in hospitalization. The virus possesses a high degree of mutagenic potential, contributing to significant antigenic diversity, which complicates immune responses and poses challenges for vaccine development and disease management. This study was conducted in Jordan from 2022 to 2023 to epidemiologically determine the prevalence and molecular characteristics of RSV.MethodsA total of 288 nasopharyngeal (NP) swabs were collected from hospitalized children at Prince Hamza Hospital, Amman, Jordan. All samples were screened for common viral and bacterial respiratory pathogens using PCR. A partial segment of the G gene of RSV was amplified for molecular characterization and phylogenetic tree analysis.ResultsViral and/or bacterial infection was identified in 71.9% (207/288) of the tested specimens. Among these, 35 samples (12.2%, 35/288) tested positive for RSV. Specific subgroup PCR analysis identified (25, 71.4%) RSV-A, (4, 11.4%) RSV-B, and (6, 17.1%) could not be identified using our set of primers. Phylogenetic tree analysis revealed that RSV-A ON1 and RSV-B BA9 genotype strains predominate in Jordan. We observed multiple substitutions in our studied sample which would drive variation in the level of antigenicity and pathogenicity of RSV. Glycosylation sites identified were consistent with previously reported studies.ConclusionThis study provides updated epidemiological data on the strains circulating in Amman, Jordan and their molecular characteristics. Continuous RSV surveillance informs vaccine development, guides public health interventions, and enables timely administration of prophylactic treatments, reducing the burden of RSV-related illness.

Laboratory validation of a clinical metagenomic next-generation sequencing assay for respiratory virus detection and discovery

Tools for rapid identification of novel and/or emerging viruses are urgently needed for clinical diagnosis of unexplained infections and pandemic preparedness. Here we developed and clinically validated a largely automated metagenomic next-generation sequencing (mNGS) assay for agnostic detection of respiratory viral pathogens from upper respiratory swab and bronchoalveolar lavage samples in <24 h. The mNGS assay achieved mean limits of detection of 543 copies/mL, viral load quantification with 100% linearity, and 93.6% sensitivity, 93.8% specificity, and 93.7% accuracy compared to gold-standard clinical multiplex RT-PCR testing. Performance increased to 97.9% overall predictive agreement after discrepancy testing and clinical adjudication, which was superior to that of RT-PCR (95.0% agreement). To enable discovery of novel, sequence-divergent human viruses with pandemic potential, de novo assembly and translated nucleotide algorithms were incorporated into the automated SURPI+ computational pipeline used by the mNGS assay for pathogen detection. Using in silico analysis, we showed that after removal of all human viral sequences from the reference database, 70 (100%) of 70 representative human viral pathogens could still be identified based on homology to related animal or plant viruses. Our assay, which was granted breakthrough device designation from the US Food and Drug Administration (FDA) in August of 2023, demonstrates the feasibility of routine mNGS testing in clinical and public health laboratories, thus facilitating a robust and rapid response to the next viral pandemic.

RE: colonization of bacterial and viral respiratory pathogens among healthcare workers in China during COVID-19 pandemic

RE: colonization of bacterial and viral respiratory pathogens among healthcare workers in China during COVID-19 pandemic

Protective efficacy of a recombinant adenovirus expressing novel dual F and HN proteins of bovine parainfluenza virus type 3

Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3+/CD8+T lymphocytes and IL-4+ cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection.

Changes in Epidemics of Respiratory Viral Infections Resulted From the COVID-19 Pandemic in Shanghai.

To investigate the changing patterns of respiratory viral infections within the context of COVID-19 pandemic. The etiological surveillance data of eight respiratory viral pathogens among patients with ARIs in Shanghai between 2013 and 2023 were analyzed to evaluate the dynamic patterns of respiratory viral infections in Shanghai compared to global other regions during pre-pandemic (period 1), pandemic (period 2), and post-pandemic (period 3) periods of COVID-19. In Shanghai and various other global regions, there was a delay of 2‒4 months in the peak positive rate of IFV and a reverse seasonality for RSV, HMPV, and HBoV was observed following the relaxation of NPIs. The proportion of patients infected with any of these eight viruses experiencing fever or high fever notably increased. During the entire study period, IFV was consistently identified as the most prevalent virus, with IFV-B as the predominant stain during period 2, and IFV-A regained its dominance following the lifting of NPIs. The proportion of RSV among children significantly increased during period 2 compared to period 1. With the relaxation of NPIs, there has been a resurgence of certain viral pathogens, accompanied by notable alterations in seasonal patterns and the spectrum of viral pathogens.

Early-life Upper Airway Microbiota are Associated with Decreased Lower Respiratory Tract Infections

Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI – namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.

A Herpes Simplex Virus Type-1-Derived Influenza Vaccine Induces Balanced Adaptive Immune Responses and Protects Mice From Lethal Influenza Virus Challenge.

Influenza virus is a major respiratory viral pathogen responsible for the deaths of hundreds of thousands worldwide each year. Current vaccines provide protection primarily by inducing strain-specific antibody responses with the requirement of a match between vaccine strains and circulating strains. It has been suggested that anti-influenza T-cell responses, in addition to antibody responses may provide the broadest protection against different flu strains. Therefore, to address this urgent need, it is desirable to develop a vaccine candidate with an ability to induce balanced adaptive immunity including cell mediated immune responses. Here, we explored the potential of VC2, a well-characterized Herpes Simplex Virus type 1 vaccine vector, as a live attenuated influenza vaccine candidate. We generated a recombinant VC2 virus expressing the influenza A hemagglutinin protein. We show that this virus is capable of generating potent and specific anti-influenza humoral and cell-mediated immune responses. We further show that a single vaccination with the VC2-derived influenza vaccine protects mice from lethal challenge with influenza virus. Our data support the continued development of VC2-derived influenza vaccines for protection of human populations from both seasonal and pandemic strains of influenza. Finally, our results support the potential of VC2-derived vaccines as a platform for the rapid development of vaccines against emerging and established pathogens, particularly respiratory pathogens.

Enteroviruses, Respiratory Syncytial Virus and Seasonal Coronaviruses in Influenza-like Illness Cases in Nepal

Acute respiratory infection is one of the leading causes of morbidity and mortality among children in low- and middle-income countries. Due to limited diagnostic capability, many respiratory pathogens causing influenza-like illness go undetected. This study aims to detect enterovirus, respiratory syncytial virus, seasonal coronavirus and respiratory pathogens other than influenza in patients with influenza-like illness. A total of 997 (54.3%) respiratory samples (collected in the years 2016–2018) were randomly selected from 1835 influenza-negative samples. The xTAG Respiratory Viral Panel (RVP) FAST v2 panel was used to detect respiratory pathogens including enterovirus/rhinovirus (EV/RV), respiratory syncytial virus (RSV) and seasonal coronavirus (HKU1, OC43, NL63 and 229E). A total of 78.7% (785/997) were positive for respiratory viruses. Of these viruses, EV/RV was detected in 36.3% (362/997), which is the highest number, followed by RSV in 13.7% (137/997). The seasonal coronaviruses HKU1 and OC43 (1.5%, 15/997), NL63 (1.2%, 12/997) and 229E (1%, 10/997) were also detected. The EV/RV-positive samples were sequenced, of which 16.7% (5/30) were confirmed as EVs and were identified as coxsackievirus (CV) types CVB5, CVB3, CV21 and CVB2. The findings of this study highlight the importance of strengthening influenza-like illness surveillance programs in the region by including other respiratory viruses in their scope besides seasonal human influenza viruses.

Epidemiologic Investigation and Genetic Variation Analysis of PRRSV, PCV2, and PCV3 in Guangdong Province, China from 2020 to 2022.

Recently, the emergence of HP-PRRSV (Highly Pathogenic porcine reproductive and respiratory syndrome virus) and the exacerbation of mixed infections of PRRSV and PCV have resulted in significant economic losses for the Chinese pig industry. This study collected a total of 226 samples suspected of infection with the aforementioned viruses from diverse pig farms in seven urban districts of central and northern Guangdong Province between 2020 and 2022. The positive rates of PRRSV, PCV2, and PCV3 in the samples were 33.2%, 37.6%, and 7.5%, respectively, and there were various mixed-infection scenarios present in the samples. This study successfully isolated multiple strains of PRRSV2 and PCV2 from their positive samples, and obtained the gene sequences of six PCV3 (ORF1 + ORF2) from samples. The associated sequences obtained were subjected to bioinformatic analysis and revealed the following:Predominantly prevalent strains of PRRSV in Guangdong Province include HP-PRRSV and NADC30-like variants, whereas PCV2 is primarily represented by the 2b and 2d subtypes. Specifically, the amino acid variation patterns exhibited by the PRRSV GP5 and NSP2 proteins of the strains sg_2108, qy_2008, and fs_2108 under environmental selective pressure are remarkably similar to the characteristics of Highly Pathogenic PRRSV; thus, it is inferred that they may possess higher virulence. The detected PCV3 strains were predominantly concentrated within the PCV3a-IM branch. All PRRSV strains involved in this study are wild-type-PRRSV (wt-PRRSV), comprising three recombinant strains and seven highly virulent strains. Among these strains, the ORF1a gene exhibited the highest variability in their genomes. Environmental selective pressure may enhance the virulence and immune evasion capabilities of PRRSV and drive mutations in the Cap proteins of PCV2 and PCV3. Conversely, PCV2 and PCV3 strains demonstrated greater stability in genetic evolution. In conclusion, this study enhances the epidemiological data regarding PRRSV, PCV2, and PCV3 in Guangdong Province, China, and is significant for the surveillance, prevention, and active control of these three diseases.

Coming to Grips With a Potentially Severe Endemic Viral Respiratory Pathogen in the General Population

Coming to Grips With a Potentially Severe Endemic Viral Respiratory Pathogen in the General Population

Development of a wastewater based infectious disease surveillance research system in South Korea.

Wastewater-based epidemiology has been used in pathogen surveillance for microorganisms at the community level. This study was conducted to determine the occurrence and trends of infectious pathogens in sewage from Yongin city and the relationships between these pathogens and the incidence of infectious diseases in the community. From December 2022 to November 2023, we collected inflow water from six wastewater treatment plants in Yongin city twice a month. The analyzed microorganisms included 15 respiratory viruses, 7 pneumonia-causing bacteria, 19 acute diarrhea-causing pathogens, SARS-CoV-2, Zika virus, hepatitis A virus, poliovirus, Mpox, and measles. They were detected through real-time PCR and conventional PCR. The concentrations of 9 pathogens among them were additionally analyzed using quantitative real time PCR. The correlation was confirmed through statistical analysis with the rate of detection for pathogens reported by the Korea Disease Control and Prevention Agency. Influenza A virus, human adenovirus, and human rhinovirus were moderately correlated (rho values of 0.45 to 0.58). Campylobacter spp. and sapovirus were strong correlated (rho values of 0.62, 0.63). Enteropathogenic E. coli, human coronavirus, and norovirus GII were very strong correlated (rho values of 0.86 to 0.92). We were able to identify the prevalence of respiratory viral infections, pneumonia, and acute diarrhea-causing pathogens in the community through wastewater-based epidemiology data. This study will be helpful in establishing a system for future surveillance of infectious diseases present in sewage.

Evaluation of the Seegene Allplex™ RV master assay for one-step simultaneous detection of eight respiratory viruses in nasopharyngeal specimens

BackgroundThe Seegene Allplex™ RV Master (RVM) assay is a one-step multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) system for detecting eight viral respiratory pathogens from nasopharyngeal swab, aspirate, and bronchoalveolar lavage specimens. The eight RVM targets are: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Influenza A (Flu A), Influenza B (Flu B), Human respiratory syncytial virus (RSV), adenovirus (AdV), rhinovirus (HRV), parainfluenza virus (PIV), and metapneumovirus (MPV). The assay is based on Seegene’s multiple detection temperature (MuDT) technology and provides cycle threshold (Ct) values for each of its viral targets upon PCR completion. ObjectiveWe aimed to evaluate the diagnostic performance of the RVM assay by calculating sensitivity, specificity, accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Percent Agreement (OPA) compared to definite diagnosis and analogous reference assays. Study designDiagnostic sensitivity, specificity, accuracy, PPV, and NPV were calculated by comparing the results of the RVM assay to that of definite diagnosis assays; while PPA, NPA, and OPA were calculated by comparing results of the RVM assay to that of analogous reference products. Definite diagnosis and reference methods comprised whole genome sequencing and PCR genotyping, the Allplex™ SARS-CoV-2/FluA/FluB/RSV and Respiratory Panels 1, 2, and 3 assays (Seegene), and the Xpert® Xpress SARS-CoV-2/FluA/FluB/RSV Plus assay (Cepheid). Reproducibility of the RVM assay using fully-automated and semi-automated nucleic acid (NA) extraction workflows and as performed by independent operators was also assessed. In total, 249 positive respiratory specimens and at least 50 negative specimens for each target tested were used for this evaluation study. ResultsSensitivity, specificity, accuracy, PPV, NPV, PPA, NPA, and OPA ranged from 95.7 % to 100 % for detecting all eight targets tested on the RVM assay. Reproducibility PPA, NPA, and OPA between automated and semi-automated NA extraction workflows were all >97.9 %, while the reproducibility PPA, NPA and OPA between independent operators were all 100 %. ConclusionThese results demonstrate a high level of sensitivity, specificity, accuracy and diagnostic predictive value of the RVM assay and high agreement with comparable reference assays in identifying all eight of its targets. Taken together, our study underscores the diagnostic utility of the RVM assay in detecting eight viral respiratory pathogens.

Molecular epidemiology of avian influenza viruses and avian coronaviruses in environmental samples from migratory bird inhabitants in Bangladesh.

Migratory birds are a natural reservoir for major respiratory viruses such as the avian influenza virus (AIV) and the avian coronavirus (AvCoV). Transmission of these viruses from migratory birds to domestic birds increases the prevalence of those diseases that cause severe economic and public health concerns in Bangladesh. The study focused on active surveillance of major respiratory viral pathogens in migratory birds, molecular identification of the viruses, and their phylogenetic origin. To conduct this study, 850 environmental samples (830 fecal samples, 10 soil samples, and 10 water samples) were collected during three consecutive winter seasons from three divisions (Dhaka, Sylhet, and Mymensingh) and pooled according to the year of collection and locations, resulting in a total of 184 tested samples. Using gene-specific primers and probes in TaqMan-and SYBR Green-based RT-qPCR assays, the samples were screened for AIV and AvCoV, respectively. Out of the 184 pooled samples, 37 were found to be positive for these respiratory pathogens. Furthermore, out of the 37 (20.11%) positive respiratory pathogens, 11.96% were AIV (n = 22) and 8.15% were AvCoV (n = 15). For the first time in Bangladesh, AIV H4N2, H4N6, and AvCoVs have been found in fecal samples from migratory birds through surveillance. Phylogenetic analyses of the HA and NA genes of AIV and the polymerase gene (Orf 1) of AvCoV revealed that these strains share a close phylogenetic relationship with the isolates from wild birds in Europe and Asia. The Bangladeshi strains with Eurasian ancestry might pose a significant threat to migratory birds flying through the Asian flyways. They might also be a potential source of virus introduction and spread to poultry raised on land. These findings emphasize the significance of ongoing AIV and AvCoV surveillance in migratory birds in Bangladesh.

A-287 Mycoplasma pneumoniae outbreak in 2023: Post pandemic resurgence of an atypical bacterial pathogen

Abstract Background Mycoplasma pnuemoniae is an atypical fastidious bacteria known to cause respiratory infections of both upper and lower tract, with a wide range of clinical presentations. M. pnuemoniae is one of the major causes of community acquired pneumonias worldwide. Almost all of the M pnuemoniae outbreak incidences have been reported in closed- community or congregate settings, such as schools, universities and colleges, and hospitals and long-term care facilities. Since the clinical symptoms of M pneumoniae overlap with other pneumonia causing pathogens, detection via multiplex PCR remains paramount for accurate and timely diagnosis to curb the infection spread. In the present study we demonstrate an unexpected increase in the detection of M. pneumoniae in the outpatient population, during 2023, as compared to the previous two years. In addition, a detailed analysis of the ICD10 diagnostic codes associated with the outbreak is also presented. Methods Respiratory samples (oropharyngeal, nasopharyngeal, sputum and EBL) summited to the HealthTrackRX laboratories were tested for the presence of M. pneumoniae and other respiratory bacterial and viral pathogens using the nanofluidic OpenArray qPCR platform (ThermoFisher, California, USA). Patient data was analyzed on the basis of age, gender and geographical location. Data was also classified in the basis of ICD10 diagnostic codes associated with the patient samples. All statistical analysis was performed using R version 3.6.0 (R Foundation for Statistical Computing). Results A total of 541,267 samples were submitted for testing at the HealthTrackRX facilities between January 1, 2021 and December 31, 2023. Only 13 samples tested positive for M. pneumoniae between 2021 (0.004%, n =3/61,498) and 2022 (0.006%, n = 10/165,423). The positivity rate of M. pneumoniae in 2023 increased to 0.19% (n = 621/314,346). The highest proportion of M. pneumoniae cases were detected from Georgia (26.8%), followed by Ohio (21.7%), Texas (8.5%) and California (6.4%). Most of the outbreak appears to be concentrated in large urban settings. Median age of the patients testing positive for M. pneumoniae was 10 (interquartile range [IQR] 8-18) years. Gender classification of the positive samples showed an almost equal distribution between females (49.8%) and males (50.1%). Co-infecting pathogens detected in samples positive for M. pneumoniae were similar in proportion to the M. pneumoniae negative population. The co-detected pathogens at a statistically significant difference were lower than the negative population. Survey of the ICD-10 codes submitted in conjunction with the samples suggest that the current outbreak is mostly associated with upper respiratory tract infections. Conclusions The present study shows an unprecedented increase in the detection of M. pneumoniae in the outpatient population in the United States during 2023. Our analysis suggests that this outbreak was not associated with any other bacterial or viral respiratory pathogen but appears to be case of “immunity debt” caused by the COVID19 pandemic. The outbreak of this atypical pathogen was concentrated in the pediatric population in large urban areas. Our study highlights the importance of performing continuous surveillance of respiratory pathogens, especially in the altered epidemiological landscape of the post COVID world.

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

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

Role of TOMM34 on NF-κB activation-related hyperinflammation in severely ill patients with COVID-19 and influenza

Highly pathogenic respiratory RNA viruses such as SARS-CoV-2 and its associated syndrome COVID-19 pose a tremendous threat to the global public health. Innate immune responses to SARS-CoV-2 depend mainly upon the NF-κB-mediated inflammation. Identifying unknown host factors driving the NF-κB activation and inflammation is crucial for the development of immune intervention strategies. Published single-cell RNA sequencing (scRNA-seq) data was used to analyze the differential transcriptome profiles of bronchoalveolar lavage (BAL) cells between healthy individuals (n=27) and patients with severe COVID-19 (n=21), as well as the differential transcriptome profiles of peripheral blood mononuclear cells (PBMCs) between healthy individuals (n=22) and severely ill patients with COVID-19 (n=45) or influenza (n=16). Loss-of-function and gain-of-function assays were performed in diverse viruses-infected cells and male mice models to identify the role of TOMM34 in antiviral innate immunity. TOMM34, together with a list of genes encoding pro-inflammatory cytokines and antiviral immune proteins, was transcriptionally upregulated in circulating monocytes, lung epithelium and innate immune cells from individuals with severe COVID-19 or influenza. Deficiency of TOMM34/Tomm34 significantly impaired the type I interferon responses and NF-κB-mediated inflammation in various human/murine cell lines, murine bone marrow-derived macrophages (BMDMs) and invivo. Mechanistically, TOMM34 recruits TRAF6 to facilitate the K63-linked polyubiquitination of NEMO upon viral infection, thus promoting the downstream NF-κB activation. In this study, viral induction of TOMM34 is positively correlated with the hyperinflammation in severely ill patients with COVID-19 and influenza. Our findings also highlight the physiological role of TOMM34 in the innate antiviral signallings. A full list of funding sources can be found in the acknowledgements section.

Prevalence and Seasonal Patterns of 16 Common Viral Respiratory Pathogens during the COVID-19 Pandemic in Gauteng Province, South Africa, 2020-2021.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic resulted in widespread morbidity and mortality, but generally, the diagnosis of other respiratory viruses was limited. This study aimed to assess the prevalence of other respiratory viruses during the 2020/2021 pandemic among patients of all ages who accessed care at public healthcare facilities in Gauteng Province, South Africa. Laboratory diagnosis for respiratory viruses, with or without SARS-CoV-2, was conducted via multiplex real-time polymerase chain reactions using respiratory specimens. A total of 1776 patients were included from 1 April 2020 to 31 March 2021, of which 766 (43.1%) were positive for respiratory viruses other than SARS-CoV-2. RV (368/1776; 20.7%) was the most prevalent, followed by RSV (304/1776; 17.1%), AdV (112/1776; 6.3%) and EV (105/1776; 5.9%). hCoV-OC43 (39/1776; 2.2%) was the most prevalent common coronavirus. SARS-CoV-2 co-infections were detected in 4.8% (24/500) of patients. Only 27.1% (482/1776) of patients were admitted to high-care or intensive care units. A decrease in respiratory virus detections was observed, except for RSV, EV and hCoV-OC43. RSV prevalence increased in 2021, while influenza A/B viruses remained undetected.

Protection efficacy and the safety of the synergy between modified Bazhen powder and PRRSV modified-live virus vaccine against HP-PRRSV in piglets.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.

Feasibility of wearable sensor signals and self-reported symptoms to prompt at-home testing for acute respiratory viruses in the USA (DETECT-AHEAD): a decentralised, randomised controlled trial

Early identification of an acute respiratory infection is important for reducing transmission and enabling earlier therapeutic intervention. We aimed to prospectively evaluate the feasibility of home-based diagnostic self-testing of viral pathogens in individuals prompted to do so on the basis of self-reported symptoms or individual changes in physiological parameters detected via a wearable sensor. DETECT-AHEAD was a prospective, decentralised, randomised controlled trial carried out in a subpopulation of an existing cohort (DETECT) of individuals enrolled in a digital-only observational study in the USA. Participants aged 18 years or older were randomly assigned (1:1:1) with a block randomisation scheme stratified by under-represented in biomedical research status. All participants were offered a wearable sensor (Fitbit Sense smartwatch). Participants in groups 1 and 2 received an at-home self-test kit (Alveo be.well) for two acute respiratory viral pathogens: SARS-CoV-2 and respiratory syncytial virus. Participants in group 1 could be alerted through the DETECT study app to take the at-home test on the basis of changes in their physiological data (as detected by our algorithm) or due to self-reported symptoms; those in group 2 were prompted via the app to self-test only due to symptoms. Group 3 served as the control group, without alerts or home testing capability. The primary endpoints, assessed on an intention-to-treat basis, were the number of acute respiratory infections presented (self-reported) and diagnosed (electronic health record), and the number of participants using at-home testing in groups 1 and 2. This trial is registered with ClinicalTrials.gov, NCT04336020. Between Sept 28 and Dec 30, 2021, 450 participants were recruited and randomly assigned to group 1 (n=149), group 2 (n=151), or group 3 (n=150). 179 (40%) participants were male, 264 (59%) were female, and seven (2%) identified as other. 232 (52%) were from populations historically under-represented in biomedical research. 118 (39%) of the 300 participants in groups 1 and 2 were prompted to self-test, with 61 (52%) successfully completing self-testing. Participants were prompted to home-test more frequently due to symptoms (41 [28%] in group 1 and 51 [34%] in group 2) than due to detected physiological changes (26 [17%] in group 1). Significantly more participants in group 1 received alerts to test than did those in group 2 (67 [45%] vs 51 [34%]; p=0·047). Of the 61 individuals who were prompted to test and successfully did so, 19 (31%) tested positive for a viral pathogen-all for SARS-CoV-2. The individuals diagnosed as positive for SARS-CoV-2 in the electronic health record were eight (5%) in group 1, four (3%) in group 2, and two (1%) in group 3, but it was difficult to confirm if they were tied to symptomatic episodes documented in the trial. There were no adverse events. In this direct-to-participant trial, we showed early feasibility of a decentralised programme to prompt individuals to use a viral pathogen diagnostic test based on symptoms tracked in the study app or physiological changes detected using a wearable sensor. Barriers to adequate participation and performance were also identified, which would need to be addressed before large-scale implementation. Janssen Pharmaceuticals.

Wastewater and clinical surveillance of respiratory viral pathogens on a university campus

Areas of dense population congregation are prone to experience respiratory virus outbreaks. We monitored wastewater and clinic patients for the presence of respiratory viruses on a large, public university campus. Campus sewer systems were monitored in 16 locations for the presence of viruses using next generation sequencing over 22 weeks in 2023. During this period, we detected a surge in human adenovirus (HAdV) levels in wastewater. Hence, we initiated clinical surveillance at an on-campus clinic from patients presenting with acute respiratory infection. From whole genome sequencing of 123 throat and/or nasal swabs collected, we identified an outbreak of HAdV, specifically of HAdV-E4 and HAdV-B7 genotypes overlapping in time. The temporal dynamics and proportions of HAdV genotypes found in wastewater were corroborated in clinical infections. We tracked specific single nucleotide polymorphisms (SNPs) found in clinical virus sequences and showed that they arose in wastewater signals concordant with the time of clinical presentation, linking community transmission of HAdV to the outbreak. This study demonstrates how wastewater-based epidemiology can be integrated with surveillance at ambulatory healthcare settings to monitor areas prone to respiratory virus outbreaks and provide public health guidance.