Respiratory Virus Outbreaks Research Articles

EpiFusion: Joint inference of the effective reproduction number by integrating phylodynamic and epidemiological modelling with particle filtering.

Accurately estimating the effective reproduction number (Rt) of a circulating pathogen is a fundamental challenge in the study of infectious disease. The fields of epidemiology and pathogen phylodynamics both share this goal, but to date, methodologies and data employed by each remain largely distinct. Here we present EpiFusion: a joint approach that can be used to harness the complementary strengths of each field to improve estimation of outbreak dynamics for large and poorly sampled epidemics, such as arboviral or respiratory virus outbreaks, and validate it for retrospective analysis. We propose a model of Rt that estimates outbreak trajectories conditional upon both phylodynamic (time-scaled trees estimated from genetic sequences) and epidemiological (case incidence) data. We simulate stochastic outbreak trajectories that are weighted according to epidemiological and phylodynamic observation models and fit using particle Markov Chain Monte Carlo. To assess performance, we test EpiFusion on simulated outbreaks in which transmission and/or surveillance rapidly changes and find that using EpiFusion to combine epidemiological and phylodynamic data maintains accuracy and increases certainty in trajectory and Rt estimates, compared to when each data type is used alone. We benchmark EpiFusion's performance against existing methods to estimate Rt and demonstrate advances in speed and accuracy. Importantly, our approach scales efficiently with dataset size. Finally, we apply our model to estimate Rt during the 2014 Ebola outbreak in Sierra Leone. EpiFusion is designed to accommodate future extensions that will improve its utility, such as explicitly modelling population structure, accommodations for phylogenetic uncertainty, and the ability to weight the contributions of genomic or case incidence to the inference.

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

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

Risk factors associated with piglet pre-weaning mortality in a Midwestern U.S. swine production system from 2020 to 2022

Piglet pre-weaning mortality (PWM) is a significant issue in the U.S. swine industry, causing economic losses and raising sustainability and animal welfare concerns. This study conducted a multivariable analysis to identify factors associated with PWM in a Midwestern U.S. swine production system. Weekly data from 47 sow farms (7207 weaning weeks) were captured from January 2020 to December 2022. Initially, 29 variables regarding farm infrastructure, productivity parameters, health status, and interventions were selected for univariate analysis to assess their association with PWM. The initial multivariable analysis included the variables with P < 0.20 in the univariate analyses. A backward stepwise model selection was conducted by excluding variables with P > 0.05, and the final multivariable model consisted of 19 significant risk factors and 6 interaction terms. The overall average PWM for the study population was 14.02 %. Yearly variations in PWM were observed, with the highest recorded in 2020 (16.61 %) and the lowest in 2021 (15.78 %). Cohorts with a pond water source, lower farrowing rate (71.9 %), higher farrowing parity (5.1), shorter gestation length (116.2 days), and using oxytocin during farrowing had increased PWM. The higher productivity parameters such as mummies rate, stillborn rate, and average total born, the higher the PWM was. Additionally, health status and intervention-related factors were associated with PWM, where higher PWM rates were observed in herds facing porcine reproductive and respiratory syndrome virus (PRRSV) outbreaks, porcine epidemic diarrhea virus (PEDV) positive, the weeks before and during feed medication, and weeks without using Rotavirus vaccine or Rotavirus feedback. Altogether, these results corroborate that PWM is a multifactorial problem, and a better understanding of the risk factors is essential in developing strategies to improve survival rates. Therefore, this study identified the major risk factors associated with PWM for groups of pigs raised under field conditions, and the results underscore the significance of data analysis in comprehending the unique challenges and opportunities inherent to each system.

An increased prevalence of carbapenem-resistant hypervirulent Klebsiella pneumoniae associated with the COVID-19 pandemic

BackgroundKlebsiella pneumoniae (Kp) is a common community-acquired and nosocomial pathogen. Carbapenem-resistant and hypervirulent (CR-hvKp) variants can emerge rapidly within healthcare facilities and impacted by other infectious agents such as COVID-19 virus. MethodsTo understand the impact of COVID-19 virus on the prevalence of CR-hvKp, we accessed Kp genomes with corresponding metadata from GenBank. Sequence types (STs), antimicrobial resistance genes, and virulence genes, and those scores and CR-hvKp were identified. We analyzed population diversity and phylogenetic characteristics of five most common STs, measured the prevalence of CR-hvKp, identified CR-hvKp subtypes, and determined associations between carbapenem resistance gene subtypes with STs and plasmid types. These variables were compared pre- and during the COVID-19 pandemic. FindingsThe proportion of CR-hvKp isolates increased within multiple STs in different continents during the COVID-19 pandemic and persistent CR-hvKp subtypes were found in common STs. blaKPC was dominant in CG258, blaKPC-2 was detected in 97 % of the ST11 CR-hvKp, blaNDM subtypes were prominent in ST147 (87.4 %) and ST307 (70.8 %); blaOXA-48 and its subtypes were prevalent in ST15 (80.5 %). The possession of carbapenemase genes was different among subclades from different origins in different periods of time within each ST. IncFIB/IncHI1B hybrid plasmids contained virulence genes and carbapenemase genes and were predominant in ST147 (67.37 %) and ST307 (56.25 %). InterpretationThe prevalence of CR-hvKp increased during the COVID-19 pandemic, which was evident by an increase in local endemic clones. This process was facilitated by the convergence of plasmids containing carbapenemase genes and virulence genes. These findings have implications for the appropriate use of antimicrobials and infection prevention and control during outbreaks of respiratory viruses and pandemic management.

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.

Computational screening combined with well-tempered metadynamics simulations identifies potential TMPRSS2 inhibitors

Type-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These serine proteases cleave viral spike proteins to expose the fusion peptide for cell entry, which is essential to the life cycle of the virus. TMPRSS2 inhibitors can also fight against respiratory viruses that employ them for cell entry. Our study combining virtual screening, all-atom molecular dynamics, and well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, and rhoifolin as promising TMPRSS2 antagonists. The binding energies obtained are − 16.3, − 15.4, − 13.6, and − 13.8 kcal/mol for vicenin-2, neohesperidin, naringin, and rhoifolin respectively. The RMSD, RMSF, PCA, DCCM, and binding free energy profiles also correlate with the stable binding of these ligands at the active site of TMPRSS2. The study reveals that these molecules could be promising lead molecules for combating future outbreaks of coronavirus and other respiratory viruses.

In silico identification of approved drugs for potential prophylactic uses against SARS-CoV-2 infection

The outbreak of Severe Acute Respiratory Syndrome Corona Virus (SARS-CoV-2) responsible for Coronavirus disease 2019 (COVID-19) constitute a major public health threat and economic burden. Despite the multifold research all over the world. COVID-19 has remained without a treatment. Hence, the urgent need to repurpose the FDA-approved drugs through in silico computational technique to identify inhibitors of SARS-CoV-2. Bioinformatics techniques were used to screen 2015 FDA- approved drugs against SARS-CoV-2 proteins and associated human protein, angiotensin-converting enzyme 2 (ACE2) to identify drug for new indication. The ligands were downloaded from Selleckchem drug data bank in SDF format. Open Babel was used to separate the ligands into their compounds and prepared for docking simulation using shell script and saved as PDBQT. Experimental crystal structures of the receptors (ACE2 and Spike proteins) were retrieved from Protein Data Bank (PDB), Autodock tools was used to prepare the proteins and saved as PDBQT files. Docking protocols were validated, molecular docking simulations were performed on a Linux platform using AutoDock Vina in quadruplicate. The binding energies (BEs) kcal/mol were calculated and expressed as mean ± standard deviation. Discovery studio was used for visualization. Density Functional Theory (DFT) was used to determine the predictive maximal inhibitory concentration (pIC50) of best hits. Ninety-one (91) new hits were identified for prophylaxis. Four (4) compounds were subjected to DFT based IC50 calculation with molnupiravir as a reference compound. Significantly, calculated IC50 of molnupiravir in Vero cells and Calu-3 were 0.299 and 0.008µM respectively while the experimental IC50 in Vero cells and Calu-3 as reported in literature were 0.3 and 0.08 µM respectively. The newly identified hits are promising therapeutic agents and there is no significant difference between the experimental IC50 of molnupiravir and the calculated IC50.

A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies—its utility during respiratory virus pandemics

ObjectivesIn hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. ResultsA total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. ConclusionsPentamidine administered IV monthly is safe and effective.

Aesculus hippocastanum extract and the main bioactive constituent β-escin as antivirals agents against coronaviruses, including SARS-CoV-2

Respiratory viruses can cause life-threatening illnesses. The focus of treatment is on supportive therapies and direct antivirals. However, antivirals may cause resistance by exerting selective pressure. Modulating the host response has emerged as a viable therapeutic approach for treating respiratory infections. Additionally, considering the probable future respiratory virus outbreaks emphasizes the need for broad-spectrum therapies to be prepared for the next pandemics. One of the principal bioactive constituents found in the seed extract of Aesculus hippocastanum L. (AH) is β-escin. The clinical therapeutic role of β-escin and AH has been associated with their anti-inflammatory effects. Regarding their mechanism of action, we and others have shown that β-escin and AH affect NF-κB signaling. Furthermore, we have reported the virucidal and broad-spectrum antiviral properties of β-escin and AH against enveloped viruses such as RSV, in vitro and in vivo. In this study, we demonstrate that β-escin and AH have antiviral and virucidal activities against SARS-CoV-2 and CCoV, revealing broad-spectrum antiviral activity against coronaviruses. Likewise, they exhibited NF-κB and cytokine modulating activities in epithelial and macrophage cell lines infected with coronaviruses in vitro. Hence, β-escin and AH are promising broad-spectrum antiviral, immunomodulatory, and virucidal drugs against coronaviruses and respiratory viruses, including SARS-CoV-2.

Viral coinfection in hospitalized patients during the COVID-19 pandemic in Southern Brazil: a retrospective cohort study

PurposeSince the worldwide spread of SARS-CoV-2, different strategies have been followed to combat the pandemic and limit virus transmission. In the meantime, other respiratory viruses continued to circulate, though at decreased rates.MethodsThis study was conducted between June and July 2022, in a hospital in the metropolitan region of Rio Grande do Sul state, in the southernmost state of Brazil. The 337 hospitalized patients included those with respiratory symptoms without delimitation of age. Reverse transcription-quantitative real-time polymerase chain reaction detected 15 different respiratory viruses and confirmed coinfections in the samples. Different statistical tests were applied to evaluate the association between associations of clinical characteristics and coinfection.ResultsSampling corresponds to 337 selected and 330 patients analyzed. The principal clinical outcome found was hospital discharge in 309 (94%) cases, while 21 (6%) resulted in death. The principal viral agents related to coinfections were Human rhinovirus, Human enterovirus, and Respiratory syncytial virus. The most frequent viral agent detected was SARS-CoV-2, with 60 (18%) infections, followed by 51 (15%) cases of Respiratory syncytial virus B (15%) and 44 (13%) cases of Human rhinovirus 1. Coinfection was mainly observed in children, while adults and the elderly were more affected by a single infection. Analyzing COVID-19 vaccination, 175 (53%) were unvaccinated while the remainder had at least one dose of the vaccine.ConclusionsThis study presents information to update the understanding of viral circulation in the region. Furthermore, the findings clarify the behavior of viral infections and possible coinfections in hospitalized patients, considering different ages and clinical profiles. In addition, this knowledge can help to monitor the population’s clinical manifestations and prevent future outbreaks of respiratory viruses.

1747. Clinical Spectrum of a Large Multi-State U.S. Cohort of Parechovirus Infection in Neonates and Young Infants

Abstract Background Severe manifestations of human parechovirus (HPeV) infection, including meningoencephalitis and sepsis, can occur in neonates and young infants. Death has rarely been reported. Rates of HPeV infection fluctuate from year to year in the community. After the home isolation during the initial COVID-19 era in 2020, waves of respiratory viral outbreaks at unusual times of the year were identified in the pediatric community in 2021 and 2022, including increased number of cases of severe HPeV infection in young infants. This study characterizes the U.S. outbreak of HPeV infections that occurred in newborns and young infants in 2022. Methods A multi-site, retrospective and prospective observational study identified hospitalized infants &amp;lt; =6 months, with a body fluid specimen positive for HPeV. IRB approval of a single protocol was obtained at each site. Data obtained included hospital summary, maternal and birth history, medications, bacterial and viral testing, and radiology results. Analysis included infants with hospitalizations from January 1 through December 31, 2022. Results 13 academic sites were enrolled, which included 8 sites achieving full IRB approval/activation and completed data collection, and 5 sites pending activation [Fig 1A]. Interim analysis shows 112 infants across eleven states hospitalized with HPeV infection with a median hospital duration of 3 days (range 0-178 d), peaking in May 2022 [Fig 1B], with a spectrum of biochemical markers [Table 1]. The median age at hospitalization was 21.5 days of life (IQR 10, 32 d). All but five infants received antibiotics during the admission, and more than half (54%) received acyclovir. Other pathogens were rarely reported [Table 2]. 45 (38%) infants received MRI brain imaging during hospitalization of which 29 were abnormal; 10 reports directly mentioning HPeV in the interpretation. A total of 51 EEGs were completed in 31 infants; 20 infants (18%) had seizures reported. 17 infants required anticonvulsants. Two infants died. Conclusion We report the first multi-site, clinical description of the 2022 U.S. outbreak of HPeV among neonates and young infants. This is the first large series of infants with HPeV to report mortality. Further development of a multi-site U.S. collaboration to improve surveillance for HPeV is needed. Disclosures Laura Filkins, PhD, Avsana Labs: Board Member|Avsana Labs: Stocks/Bonds|Biofire Diagnostics: Grant/Research Support Claudia M. Espinosa, MD, MSc, AstraZeneca: Grant/Research Support|Enanta: Grant/Research Support|Jansen and Jansen: Advisor/Consultant|Kentucky Rural Health Association: Honoraria|Merck: Grant/Research Support|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Sobi: Dinner Joseph A. Bocchini, Jr., MD, Avalere: Advisor/Consultant|Enanta: Site PI on multicenter clinical trials, contract with employer|Moderna: Advisor/Consultant|Novavax: Sub-I on multicenter clinical trials, contract with employer|Pfizer: Advisor/Consultant|Pfizer: Site PI on multicenter clinical trials, contract with employer|Regeneron: Site PI on multicenter clinical trials, contract with employer|Sobi: Advisor/Consultant|Valneva: Advisor/Consultant Roberto P. Santos, MD, MSCS, Eli Lilly (SARS-CoV-2, baricitinid) - Site Open for Enrollment on March 8, 2023: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI|Eli Lilly (SARS-CoV-2, LY3819253, LY3832479) - study discontinuation on January 3, 2022: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI|JNJ (RSV, rilematovir) - study discontinuation on March 1, 2022: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI|MSD (HIV, islatravir, doravirine) - study discontinuation on December 6, 2022: Industry-sponsored clinical trials with research contract awarded to the University of Mississippi Medical Center with RPS as site PI Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support David W. Kimberlin, MD, Gilead: Grant/Research Support|Gilead: I served as site PI on Gilead's study of remdesivir in pediatric patients. All monies went directly to my university and not to me.

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

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

Respiratory virus infections in decedents in a large, urban medical examiner's office

ObjectiveMost respiratory virus surveillance relies on medically attended respiratory illness, but an understanding of the true patterns of infection independent of care-seeking behaviour would enhance clinical and public health responses to respiratory virus outbreaks. We evaluated the potential of decedent surveillance by estimating the burden of respiratory virus infection in decedents in a large, urban medical examiner's office. Study designObservational. MethodsIn 2020–2022, we tested nasopharyngeal swabs from 4121 decedents in Detroit, Michigan for 15 respiratory viruses, including SARS-CoV-2, respiratory syncytial virus, and influenza virus A and B. We analysed infection prevalence over time and by age, sex, race/ethnicity, and manner of death. ResultsOf 4113 valid tests, 30.2% were positive for at least one virus, and 6.1% were positive for multiple viruses. All viruses were detected except for influenza A/H1N1 and influenza B. The most prevalent viruses were SARS-CoV-2 (15.7%), rhinovirus (11.2%), and adenovirus (4.9%), which were detected in all months. Most viruses exhibited decreasing prevalence with age, higher prevalence among Black and Hispanic than among White decedents and lower prevalence among deaths from natural causes; SARS-CoV-2 was a notable exception to the patterns by age and manner of death, instead reflecting community trends in catchment counties. ConclusionsThere was high prevalence and diversity of respiratory viruses in decedents entering a large, urban medical examiner's office. Decedent surveillance could offer a clearer picture of the true underlying burden of infection, motivating public health priorities for intervention and vaccine development, and augmenting data for real-time response to respiratory virus outbreaks.

Wastewater Surveillance Data as a Complement to Emergency Department Visit Data for Tracking Incidence of Influenza A and Respiratory Syncytial Virus - Wisconsin, August 2022-March 2023.

Wastewater surveillance has been used to assist public health authorities in tracking local transmission of SARS-CoV-2. The usefulness of wastewater surveillance to track community spread of other respiratory pathogens, including influenza virus and respiratory syncytial virus (RSV), is less clear. During the 2022-23 respiratory diseases season, concentrations of influenza A virus and RSV in wastewater samples in three major Wisconsin cities were compared with emergency department (ED) visits associated with these pathogens. In all three cities, higher concentrations of influenza A virus and RSV in wastewater were associated with higher numbers of associated ED visits (Kendall's tau range=0.50-0.63 for influenza-associated illness and 0.30-0.49 for RSV-associated illness). Detections of both influenza A virus and RSV in wastewater often preceded a rise in associated ED visits for each pathogen, and virus material remained detectable in wastewater for up to 3 months after pathogen-specific ED visits declined. These results demonstrate that wastewater surveillance has the potential to complement conventional methods of influenza and RSV surveillance, detecting viral signals earlier and for a longer duration than do clinical data. Continued use of wastewater surveillance as a supplement to established surveillance systems such as ED visits might improve local understanding and response to seasonal respiratory virus outbreaks.

Hylin-a1: A Pan-Inhibitor against Emerging and Re-Emerging Respiratory Viruses.

Pandemic and epidemic outbreaks of respiratory viruses are a challenge for public health and social care system worldwide, leading to high mortality and morbidity among the human populations. In light of the limited efficacy of current vaccines and antiviral drugs against respiratory viral infections and the emergence and re-emergence of new viruses, novel broad-spectrum antiviral drugs are needed for the prevention and treatment of these infections. Antimicrobial peptides with an antiviral effect, also known as AVPs, have already been reported as potent inhibitors of viral infections by affecting different stages of the virus lifecycle. In the present study, we analyzed the activity of the AVP Hylin-a1, secreted by the frog Hypsiboas albopunctatus, against a wide range of respiratory viruses, including the coronaviruses HCoV-229E and SARS-CoV-2, measles virus, human parainfluenza virus type 3, and influenza virus H1N1. We report a significant inhibitory effect on infectivity in all the enveloped viruses, whereas there was a lack of activity against the naked coxsackievirus B3. Considering the enormous therapeutic potential of Hylin-a1, further experiments are required to elucidate its mechanism of action and to increase its stability by modifying the native sequence.

Risk factors for SARS-CoV-2 infection during the early stages of the COVID-19 pandemic: a systematic literature review.

Identifying SARS-CoV-2 infection risk factors allows targeted public health and social measures (PHSM). As new, more transmissible variants of concern (VoC) emerge, vaccination rates increase and PHSM are eased, it is important to understand any potential change to infection risk factors. The aim of this systematic literature review is to describe the risk factors for SARS-CoV-2 infection by VoC. A literature search was performed in MEDLINE, PubMed and Embase databases on 5 May 2022. Eligibility included: observational studies published in English after 1 January 2020; any age group; the outcome of SARS-CoV-2 infection; and any potential risk factors investigated in the study. Results were synthesized into a narrative summary with respect to measures of association, by VoC. ROBINS-E tool was utilized for risk of bias assessment. Of 6,197 studies retrieved, 43 studies were included after screening. Common risk factors included older age, minority ethnic group, low socioeconomic status, male gender, increased household size, occupation/lower income level, inability to work from home, public transport use, and lower education level. Most studies were undertaken when the ancestral strain was predominant. Many studies had some selection bias due to testing criteria and limited laboratory capacity. Understanding who is at risk enables the development of strategies that target priority groups at each of the different stages of a pandemic and helps inform vaccination strategies and other interventions which may also inform public health responses to future respiratory infection outbreaks. While it was not possible to determine changes to infection risk by recent VoC in this review, the risk factors identified will add to the overall understanding of the groups who are at greatest risk of infection in the early stages of a respiratory virus outbreak. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022330706, PROSPERO [CRD42022330706].

Unexpected Increase in Invasive Group A Streptococcal Infections in Children After Respiratory Viruses Outbreak in France: A 15-Year Time-Series Analysis.

In a 15-year pediatric time-series analysis, we showed a rise of invasive Group A streptococcal (iGAS) infections since October 2022, mainly involving pleural empyema, simultaneously to a respiratory virus outbreak. Physicians should be aware of this increased risk of pediatric iGAS infections, especially in settings with intense respiratory viruses' circulation.

Trends in Hospitalization and Mortality for Influenza and Other Respiratory Viruses during the COVID-19 Pandemic in the United States.

Seasonal epidemics of respiratory viruses, respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses (PIVs), and human metapneumovirus (MPV) are associated with a significant healthcare burden secondary to hundreds of thousands of hospitalizations every year in the United States (US) alone. Preventive measures implemented to reduce the spread of SARS-CoV-2 (COVID-19 infection), including facemasks, hand hygiene, stay-at-home orders, and closure of schools and local/national borders may have impacted the transmission of these respiratory viruses. In this study, we looked at the hospitalization and mortality trends for various respiratory viral infections from January 2017 to December 2020. We found a strong reduction in all viral respiratory infections, with the lowest admission rates and mortality in the last season (2020) compared to the corresponding months from the past three years (2017-2019). This study highlights the importance of public health interventions implemented during the COVID-19 pandemic, which had far-reaching public health benefits. Appropriate and timely use of these measures may help to reduce the severity of future seasonal respiratory viral outbreaks as well as their burden on already strained healthcare systems.

Infection dynamics, transmission, and evolution after an outbreak of porcine reproductive and respiratory syndrome virus.

The present study was aimed at describing the infection dynamics, transmission, and evolution of porcine reproductive and respiratory syndrome virus (PRRSV) after an outbreak in a 300-sow farrow-to-wean farm that was implementing a vaccination program. Three subsequent batches of piglets (9-11 litters/batch) were followed 1.5 (Batch 1), 8 (Batch 2), and 12 months after (Batch 3) from birth to 9 weeks of age. The RT-qPCR analysis showed that shortly after the outbreak (Batch 1), one third of sows were delivering infected piglets and the cumulative incidence reached 80% by 9 weeks of age. In contrast, in Batch 2, only 10% animals in total got infected in the same period. In Batch 3, 60% litters had born-infected animals and cumulative incidence rose to 78%. Higher viral genetic diversity was observed in Batch 1, with 4 viral clades circulating, of which 3 could be traced to vertical transmission events, suggesting the existence of founder viral variants. In Batch 3 though only one variant was found, distinguishable from those circulating previously, suggesting that a selection process had occurred. ELISA antibodies at 2 weeks of age were significantly higher in Batch 1 and 3 compared to Batch 2, while low levels of neutralizing antibodies were detected in either piglets or sows in all batches. In addition, some sows present in Batch 1 and 3 delivered infected piglets twice, and the offspring were devoid of neutralizing antibodies at 2 weeks of age. These results suggest that a high viral diversity was featured at the initial outbreak followed by a phase of limited circulation, but subsequently an escape variant emerged in the population causing a rebound of vertical transmission. The presence of unresponsive sows that had vertical transmission events could have contributed to the transmission. Moreover, the records of contacts between animals and the phylogenetic analyses allowed to trace back 87 and 47% of the transmission chains in Batch 1 and 3, respectively. Most animals transmitted the infection to 1-3 pen-mates, but super-spreaders were also identified. One animal that was born-viremic and persisted as viremic for the whole study period did not contribute to transmission.

An assessment of enhanced biosecurity interventions and their impact on porcine reproductive and respiratory syndrome virus outbreaks within a managed group of farrow-to-wean farms, 2020-2021.

Porcine reproductive and respiratory syndrome virus (PRRSV) has been a challenge for the U.S. swine industry for over 30 years, costing producers more than $600 million annually through reproductive disease in sows and respiratory disease in growing pigs. In this study, the impact of enhanced biosecurity practices of site location, air filtration, and feed mitigation was assessed on farrow-to-wean sites managed by a large swine production management company in the Midwest United States. Those three factors varied in the system that otherwise had implemented a stringent biosecurity protocol on farrow-to-wean sites. The routine biosecurity followed commonplace activities for farrow-to-wean sites that included but were not limited to visitor registration, transport disinfection, shower-in/shower-out procedures, and decontamination and disinfection of delivered items and were audited. Logistic regression was used to evaluate PRRSV infection by site based on the state where the site is located and air filtration use while controlling for other variables such as vaccine status, herd size, and pen vs. stall. A descriptive analysis was used to evaluate the impact of feed mitigation stratified by air filtration use. Sites that used feed mitigates as additives in the diets, air filtration of barns, and that were in less swine-dense areas appeared to experience fewer outbreaks associated with PRRSV infection. Specifically, 23.1% of farms that utilized a feed mitigation program experienced PRRSV outbreaks, in contrast to 100% of those that did not. Sites that did not use air filtration had 20 times greater odds of having a PRRSV outbreak. The strongest protective effect was found when both air filtration and feed mitigation were used. Locations outside of Minnesota and Iowa had 98.5-99% lesser odds of infection as well. Enhanced biosecurity practices may yield significant protective effects and should be considered for producers in swine-dense areas or when the site contains valuable genetics or many pigs.