Respiratory Virus Infection Research Articles

IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections.

Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1+ neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1- counterpart. VRI-induced regulatory PD-L1+ neutrophils were generated remotely in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation, and reduced expression of resolving factors. These findings suggest that PD-L1+ neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.

Antibiotic Overuse in Pediatric Patients Hospitalized with RSV, COVID-19, and Influenza

Abstract Background Children hospitalized with viral respiratory tract infections (RTIs) are often treated with antibiotics due to concern for bacterial co-infection, although most do not have concurrent bacterial infections. This practice leads to unnecessary antibiotic treatment, which can lead to development of resistant bacteria and adverse events. The extent of antibiotic overuse in hospitalized children with community-onset viral RTI has not been well-quantified in recent years and may have worsened during the COVID-19 pandemic. The objectives of this study were to quantify and compare the extent of antibiotic overtreatment and to determine predictors of antibiotic use post-COVID-19 pandemic in children hospitalized with RSV, COVID-19, and influenza. Methods We performed a single center retrospective study evaluating percentages of antibiotic use and bacterial co-infection among children and adolescents aged <19 years old, hospitalized with respiratory syncytial virus (RSV), influenza, or SARS-CoV-2 between April 2020 and May 2023. Bacterial infection was defined as growth of bacteria from any specimen source, including blood, urine, pleural fluid, cerebrospinal fluid, and respiratory secretions, excluding common contaminants like coagulase-negative Staphylococci. Predictors of antibiotic treatment were determined using multivariable logistic regression. Results During the study period 1,718 patients were included (1022 with RSV, 188 with influenza, 535 with COVID-19). RSV patients were younger and more likely to be in the ICU than influenza or COVID-19 patients. The overall proportion of patients with culture-confirmed bacterial co-infection was low at 8% and did not differ greatly by virus type (8% for influenza, 6.9% for RSV, 10.3% for COVID-19, p=0.03). The proportion of children receiving antibiotics was higher for influenza than for other viruses (60.6% for influenza, 41.2% for RSV, and 48.6% for COVID-19, p < 0.001). Among patients with the lowest severity of illness (with normal inflammatory markers [PCT <0.5 ug/mL or CRP <50 mg/L] and not admitted to the ICU), 7.3% had a culture-confirmed bacterial infection while 48.1% received antibiotics. Independent predictors for receiving antibiotics were elevated inflammatory markers (C-reactive protein or procalcitonin), having >3 comorbidities, mechanical ventilation, and influenza diagnosis. Conclusion In children hospitalized with community-onset viral RTIs, antibiotic treatment is substantially higher than the burden of culture-confirmed bacterial infection, suggesting antibiotic overuse. Antibiotic use was greater for patients with influenza than for those with RSV or COVID-19. Antibiotic overuse was estimated to occur in over 40% of patients with low severity of illness. Stewardship programs can use this data to design interventions to promote more judicious antibiotic use. Figure 1. Rates of bacterial co-infection and antibiotic utilization among patients hospitalized with influenza, RSV, and COVID. Blue, percentage of patients who had a culture-confirmed bacterial infection; orange, percentage of patients who received any antibiotics; green, percentage of patients who received >3 days of antibiotics.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

We describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated positive correlation with interferon-related protein expression and negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insight into the lower airway and systemic proteome of severe pediatric vLRTI.

The Recent Increase in Invasive Bacterial Infections: A Report From the National COVID Cohort Collaborative

Background: When coronavirus disease 2019 (COVID-19) mitigation efforts waned, viral respiratory infections (VRIs) surged, potentially increasing the risk of postviral invasive bacterial infections (IBIs). We sought to evaluate the change in epidemiology and relationships between specific VRIs and IBIs [complicated pneumonia, complicated sinusitis and invasive group A streptococcus (iGAS)] over time using the National COVID Cohort Collaborative (N3C) dataset. Methods: We performed a secondary analysis of all prospectively collected pediatric (<19 years old) and adult encounters at 58 N3C institutions, stratified by era: pre-pandemic (January 1, 2018, to February 28, 2020) versus pandemic (March 1, 2020, to June 1, 2023). We compared the characteristics and outcomes of patients with prespecified VRIs and IBIs, including correlation between VRI cases and subsequent IBI cases. Results: We identified 965,777 pediatric and 9,336,737 adult hospitalizations. Compared with pre-pandemic, pandemic-era children demonstrated higher mean monthly cases of adenovirus (121 vs. 79.1), iGAS (5.8 vs. 3.3), complicated pneumonia (282 vs. 178) and complicated sinusitis (29.8 vs. 16.3), P < 0.005 for all. Among pandemic-era children, peak correlation between RSV cases and subsequent complicated sinusitis cases occurred with a 60-day lag (correlation coefficient 0.56, 95% confidence interval: 0.52–0.59, P < 0.001) while peak correlation between influenza and complicated sinusitis occurred with a 33-day lag (0.55, 0.51–0.58, P < 0.001). Correlation among other VRI–IBI pairs was modest during the pandemic and often lower than during the pre-pandemic era. Conclusions: Since COVID-19 emerged, mean monthly cases of iGAS, complicated pneumonia, and complicated sinusitis have been higher. Pandemic-era RSV and influenza cases were correlated with subsequent cases of complicated sinusitis in children. However, many other VRI–IBI correlations decreased during the pandemic.

Arterial Thrombosis in Acute Respiratory Infections: An Underestimated but Clinically Relevant Problem

During the COVID-19 pandemic, there was increased interest in the issue of thrombotic complications of acute respiratory infections. Clinical reports and pathological studies have revealed that thrombus formation in COVID-19 may involve the venous and arterial vasculature. As thrombotic complications of infectious respiratory diseases are increasingly considered in the context of COVID-19, the fact that thrombosis in lung diseases of viral and bacterial etiology was described long before the pandemic is overlooked. Pre-pandemic studies show that bacterial and viral respiratory infections are associated with an increased risk of thrombotic complications such as myocardial infarction, ischemic stroke, pulmonary embolism, and other critical illnesses caused by arterial and venous thrombosis. This narrative review article aims to summarize the current evidence regarding thrombotic complications and their pathogenesis in acute lower respiratory tract infections.

Comparative study on the epidemiological characteristics and hazards of respiratory syncytial virus and influenza virus infections among elderly people

ObjectiveTo investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections.MethodsIn this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted.ResultsAmong 1,894 cases included, the RSV positivity rate was 5.91% during the 2023–2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection.ConclusionsDuring the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients.

Hormonal status in women with respiratory viral infections during critical periods

Pregnancy and menopause are critical periods in a woman’s life. Due to physiological changes in the neuroendocrine system regulation, susceptibility to respiratory viral infections increases in these periods, while affecting all organs and systems of the human body. The aim of this review was to analyze the literature data on the effect of acute respiratory viral infections on neuroendocrine regulation in women during pregnancy and menopause. We reviewed full-text publications in the public domain from the PubMed, eLibrary.ru, and Google Scholar databases with a coverage period of more than twenty years (2000–2023). Disruptions of the progesterone and estrogen production during infection with the influenza A (H1N1) and influenza B viruses have been shown in experimental studies. Hormonal status changes in pregnant women are detected during infection with the influenza A virus (H3N2) and depend on antiviral antibody titers and the presence of fetoplacental insufficiency. Pregnant women with COVID-19 may experience changes in the brain structure activities, as indicated by a high frequency of those in olfactory sensitivity and psychoemotional disorders. During menopause, infection with the SARS-CoV-2 virus leads to changes in the production of thyroxine, prolactin, estradiol, testosterone, cortisol, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate.

Inhaled GM-CSF administered during ongoing pneumovirus infection alters myeloid and CD8 T cell immunity without affecting disease outcome.

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pleiotropic cytokine, able to promote both myelopoiesis and activation of immune cells. Particularly in the lung, GM-CSF plays an important homeostatic role in the development and maintenance of alveolar macrophages, and is therefore considered to play a role in respiratory virus infections such as influenza and SARS-CoV-2, although the benefits of GM-CSF treatment in clinical studies remain inconclusive. To address this, we tested inhaled GM-CSF treatment in the Pneumonia Virus of Mice (PVM) mouse model. Our findings show that local GM-CSF therapy during PVM disease increased local neutrophilia and monocyte-derived cell influx, but diminished CD8+ T cells responses. Despite this, the observed effects on T cells and myeloid cells did not result in an altered clinical outcome during PVM infection. We conclude that inhaled GM-CSF therapy cannot be considered as a universal protective therapy in respiratory virus infections.

Impact of the method of delivery and feeding practice on the gut microbiome of infants in the postnatal period

BACKGROUND: The increasing frequency of cesarean sections and artificial feeding creates a predisposition to allergic diseases, obesity, and diabetes mellitus. Pathogenesis of these involves changes in the gut microbiome of infants. AIM: The aim of this study was to evaluate the impact of the method of delivery and feeding practice on the gut microbiome of infants. MATERIALS AND METHODS: This study included 103 infants aged 4-6 weeks (group 1: 39 infants born vaginally and breastfed; group 2: 10 infants born vaginally and formula-fed; group 3: 31 infants born by caesarean section and breastfed; group 4: 23 infants born by caesarean section and formula-fed), each of whom had stool collected for 16S ribosomal RNA gene sequencing. RESULTS: We found differences in the relative abundance of Akkermansia spp. [34.07 (29.29–38.85)% in group 4 and 0.01 (0.01–0.02)% in group 1; p = 0.011], Bifidobacterium spp. [30.68 (21.65–39.41)% in group 1 and 17.08 (9.86–21.68)% in group 4, (p = 0.002); 31.46 (24,30–52.97)% in group 3 and 17.08 (9.86–21.68)% in group 4 (p = 0.001)], and Enterococcus spp. [4.69 (1.01–8.59)% in group 3 and 0.58 (0.12–1.87)% in group 1 (p = 0.003); 4.29 (2.07–6.96)% in group 4 and 0.58 (0.12–1.87)% in group 1 (p = 0.001)]. The coefficient of correlation adaptometry was maximum for groups of infants who were breastfed. Analysis of the morbidity of infants in the first year of life revealed differences in the incidence of acute respiratory viral infections between infants in groups 1 and 4 (17.9 and 78.3%, respectively; p = 0.0064), as well as groups 3 and 4 (32.2 and 78.3%, respectively; p = 0.018). CONCLUSIONS: The relative abundance of Bifidobacterium spp. depends on feeding practice to a greater extent than on the method of delivery. The method of delivery affects the relative abundance of opportunistic bacteria such as Enterococcus spp. Correlation analysis demonstrated the role of breastfeeding as a mechanism for “learning” and maturing the immune system of children.

Common viral respiratory infections in children with cancer during the COVID-19 pandemic: a multicenter study from Türkiye.

Microbiologic confirmation of respiratory tract infections gained importance during the coronavirus disease 2019 (COVID-19) pandemic. This study retrospectively evaluated seasonal distribution, clinical presentation, and complications of respiratory viral infections (RVIs) other than COVID-19 in children with cancer during and after the pandemic lockdown. Two hundred and sixty-five inpatient and outpatient RVI episodes in 219 pediatric cancer patients confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) panels from 13 centers were enrolled. Eighty-six (32.5%) of the total 265 episodes occurred in 16 months corresponding to the lockdowns in Türkiye, and the remaining 67.5% in 10 months thereafter. Human rhinovirus/enterovirus (hRE) (48.3%) was the most common agent detected during and after lockdown. Parainfluenza virus (PIV) (23.0%), influenza virus (9.8%), and respiratory syncytial virus (RSV) (9.1%) were the other common agents. The 28.7% of episodes were lower respiratory tract infections (LRTIs), and complications and mortality were higher than upper respiratory tract infections (URTIs) (25.0% vs 5.3%). Bacteremia was identified in 11.5% of culture-drawn episodes. Treatment delay in one-third and death within four weeks after RVI in 4.9% of episodes were observed. During the pandemic, fewer episodes of RVIs occurred during the lockdown period. Respiratory viruses may cause complications, delays in treatment, and even death in children with cancer. Therefore, increased awareness of RVIs and rapid detection of respiratory viruses will benefit the prevention and, in some cases, abrupt supportive and some antiviral treatment of RVI in children with cancer.

Association between Respiratory Virus Infection and Development of De Novo Donor-Specific Antibody in Lung Transplant Recipients.

Chronic lung allograft dysfunction (CLAD) is the most common cause of long-term lung allograft failure. Several factors, including respiratory virus infection (RVI), have been associated with CLAD development, but the underlying mechanisms of these associations are not well understood. We hypothesize that RVI in lung transplant recipients elicits the development of donor-specific antibodies (DSAs), thus providing a mechanistic link between RVI and CLAD development. To test this hypothesis, we retrospectively evaluated for the presence of HLA antibodies in a cohort of lung transplant recipients with symptomatic RVI within the first four months post-transplant using sera at two time points (at/directly after the transplant and following RVI) and time-matched controls without RVI (post-transplant). We found a trend toward the development of de novo DSAs in those with symptomatic RVI versus controls [6/21 (29%) vs. 1/21 (5%), respectively, p = 0.09]. No cases or controls had DSA at baseline. We also found increased rates of CLAD and death among those who developed class II DSA versus those who did not (CLAD: 5/7 (71.4%) vs. 19/34 (54.3%), death: 5/7 (71.4%) vs. 17/35 (48.6%)). Prospective studies evaluating the temporal development of DSA after RVI in lung transplant patients and the subsequent outcomes are warranted.

7659 Iodinated Contrast Induced Thyrotoxicosis Leading to Takotsubu Cardiomyopathy

Abstract Disclosure: A. Jain: None. E. Naous: None. S. Sedrakyan: None. A.T. Sweeney: None. Background: Thyrotoxicosis may cause many cardiovascular manifestations including tachycardia, hypertension, atrial fibrillation and heart failure. Iatrogenic exposure to iodinated contrast media (ICM) precipitating iodine induced thyrotoxicosis (or the Jod-Basedow phenomenon) is often overlooked. Here, we describe a case of iodine induced thyrotoxicosis leading to takotsubu cardiomyopathy, following multiple exposures to ICM. Case Presentation: An 88-year-old male with a history of hypertension, dyslipidemia, chronic obstructive pulmonary disease, and an ED visit one month ago for hemoptysis for which a CT Angiography (CTA) of the chest was obtained (which excluded Pulmonary Embolism(PE)), presented with fever and shortness of breath. On physical examination his temperature was 100.3F, heart rate was 104bpm, blood pressure 130/62mmHg, respiratory rate was 20/min and saturation was 88% (room air). He was frail but his examination was otherwise unremarkable. Electrocardiogram (EKG) revealed sinus tachycardia. Chest CTA excluded PE. Transthoracic echocardiogram (TTE) showed an ejection fraction (EF) of 73% and no wall motion abnormalities. He was admitted to the hospital for a viral upper respiratory infection and was treated conservatively with bronchodilators. Odynophagia prompted a CT with contrast of the neck soft tissue, which was unrevealing. He was planned to be discharged the next day, but overnight developed severe abdominal pain, and atrial fibrillation with a rapid ventricular response (Troponin t was 191 ng/L (normal {nl}: <9 ng/L)). EKG showed new T-wave inversions in the anterolateral leads, raising a suspicion of myocardial ischemia. A repeated TTE revealed a new drop in EF from 73 to 41%, with new apical akinesis, suspicious for takotsubo cardiomyopathy. CT of the abdomen with contrast was unrevealing. Lab results showed a suppressed TSH of <0.01uIU/mL (nl: 0.34-5.60 uIU/mL), elevated FT4 of 13ng/dL (nl: 0.93-1.70 ng/dL), and TSI 4.97 IU/ L (nl: 0-0.55 IU/ L). Endocrinology was consulted. His thyroid examination was normal, and he had no eye findings. Neck ultrasound revealed a homogeneous thyroid gland without any nodules. His clinical course was consistent with the diagnosis of acute thyrotoxicosis precipitating takotsubu cardiomyopathy. He likely developed iodine induced thyrotoxicosis from multiple exposures to ICM, in a background of previously undiagnosed Graves’ disease. Discussion: Screening for thyroid disease is critical in patients with new onset tachyarrhythmias and stress cardiomyopathy. Iodine induced thyrotoxicosis typically presents after patients with underlying thyroid disease are exposed to iodinated contrast. Prior to ordering studies requiring ICM, it is important to thoroughly evaluate patients for possible pre-existing thyroid disease. Presentation: 6/2/2024

6423 The Storm in a Healthy 26-year-old Hispanic Female

Abstract Disclosure: P.M. Reyes-Torres: None. M. Hernandez-Hernandez: None. Uncontrolled hyperthyroidism can cause thyrotoxicosis and lead to end-organ dysfunction known as thyroid storm. The incidence is .20 and .76 per 100,000 persons per year, with an incidence of 4.8–5.6 per 100,000 hospitalized patients. Of those hospitalized with thyrotoxicosis in the U.S., thyroid storm is diagnosed in 16%. Most commonly affects females, middle-aged patients, and Caucasians. Can be precipitated by acute illnesses, surgery, or non-compliance with medications. Symptoms are characterized by fever, cardiac and gastrointestinal dysfunction, and altered mentation along with impaired thyroid function tests.A 26-year-old Hispanic female presented to our ER complaining of palpitations, general malaise, dysphagia, and fevers after attending a social event 3 days before. Physical examination revealed a fever of 101F, restless patient with pressured speech, and diffusely enlarged non-tender thyroid without discrete nodules. Labs were remarkable for WBC: 12 000, urinalysis, b-HCG, and CXR were all negative. Burch-Wartofsky Point Scale: 55 and biochemical tests (TSH: 0.005 ml/UL, free T4 >5 ng/dL, Total T3: 8.5 ng/mL, Total T4: 28.87 uG/DL, Thyroglobulin 34.81 ng/mL) for which diagnosis of thyroid storm was made. She was transferred to the ICU and treatment was initiated with fluids, Propranolol 60 mg PO q4hrs, PTU 250 mg PO q4hrs, and Hydrocortisone 300 mg IV as loading dose then 100mg IV q8hrs. TSI and TRAb were ordered. Thyroid US remarkable for bulky thyroid gland with heterogeneous, increased vascularity, no obvious cystic/solid lesions seen. Repeated tests showed a decreasing trend of free T4: 4.71 ng/dL and Total T3: 2.42ng/dL for which PTU was discontinued and Methimazole 15 mg PO BID was started. Five days after treatment started, the patient continued symptom-free and was discharged with Propranolol 60 mg PO q6hrs and Methimazole 15 mg PO BID. TSI and TRAb samples were obtained but results were pending before discharge. Follow-up was scheduled in 2 weeks with routine labs but the patient was lost to follow-up.This case highlights the importance of early recognition and treatment of thyroid storm in Hispanics, undiagnosed patients given the presenting nonspecific, life-threatening symptoms. We conclude that our patient's cause of thyrotoxicosis was an undiagnosed case of Graves Disease and the storm was most likely triggered by an upper viral respiratory tract infection. This case could potentially help physicians identify hyperthyroidism in an earlier phase, reducing incidence, mortality, and hospitalizations of thyroid storm since a variety of mimics make the diagnosis challenging. Furthermore, we could contribute to updated statistical knowledge regarding the risk of patients with thyrotoxicosis developing thyroid storm which despite advancements in technology, are currently lacking. Presentation: 6/1/2024

The bidirectional interplay of obstructive sleep apnea and viral respiratory infections in children: A novel opportunity for primary prevention.

Obstructive sleep apnea (OSA) and viral respiratory infections are highly prevalent conditions in children and a major cause of respiratory morbidity in this age group. Severe viral respiratory infections are a known risk factor for pediatric OSA, which is primarily caused by hypertrophy of upper airway lymphoid tissues (adenoids and tonsils). This review examines recent progress in understanding early-life development of lymphoid tissues in the human upper airway, with a particular focus on how respiratory viruses may influence this process and contribute to OSA pathogenesis. It also explores the bidirectional relationship between OSA and severe viral infections, highlighting the need for ongoing monitoring and novel primary prevention strategies to address these interconnected conditions.

Resolving the Structure of a Guanine Quadruplex in TMPRSS2 Messenger RNA by Circular Dichroism and Molecular Modeling.

The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.

Protein and transcriptional biomarker profiling may inform treatment strategies in lower respiratory tract infections by indicating bacterial-viral differentiation.

Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.

Aging enhances pro-atrogenic gene expression and skeletal muscle loss following respiratory syncytial virus infection.

Aging and many age-related health conditions are associated with skeletal muscle loss. Furthermore, older adults are more susceptible to severe respiratory infections, which can in turn lead to muscle wasting. The mechanisms by which respiratory viral infection can impact skeletal muscle in older adults are not well understood. We determined the effects of acute infection with respiratory syncytial virus (RSV) on the lung and skeletal muscle of aged mice. RSV infection caused more severe disease in aged mice with enhanced weight loss, reduced feeding, higher viral load, and greater airway inflammation. Aged but not young mice showed decreased leg muscle weight at the peak of illness and decreased size of leg muscle fibers. Aged mice increased muscle-specific expression of atrophy-promoting enzymes (Atrogin-1 and MuRF-1) and failed to increase the rate of muscle protein synthesis during RSV infection. In aged mice, the changes in Atrogin-1 and MuRF-1 gene expression in skeletal muscle correlated with IL-6 levels in the lungs. These findings indicate that RSV infection of aged mice provides a model for studying the diverse adverse systemic consequences of respiratory viral infections on health and wellbeing in older adults.

B-152 Analysis of carbonyl compounds in exhaled breath for detection of COVID-19

Abstract Background COVID-19 pandemic has caused enormous loss of lives and economic disruption. The global crisis has resulted in more than 700 million infections and 7 million deaths worldwide. Rapid screening and detection of highly infectious respiratory diseases is a key for preventing and curbing future epidemic and pandemic. The objective of this work is to develop a novel breath analysis technique for detection of COVID-19 using chemoselective capture of carbonyl compounds in exhaled breath for analysis by gas chromatography-mass spectrometry (GC-MS). Respiratory viral infection causes oxidative stress and inflammation in its host body which leads to production of higher levels of some carbonyl compounds through oxidation of lipids and could be detected in exhaled breath. This breath analysis technique can be rapidly adapted for screening infectious respiratory diseases for future epidemic and potential pandemic. Methods A total of 237 subjects were enrolled in this study. Of these, 142 were COVID-19 positive and 95 were negative. One liter exhaled breath in Tedlar bags from both COVID-19 positive and negative subjects confirmed by reverse transcriptase polymerase chain reaction between April 2022 and September 2023. The collected one liter breath samples were completely evacuated through a cartridge packed with silica particles in 2-3 minutes. Silica particles were coated with a reactive aminooxy agent for capture of carbonyl compounds in the breath samples through oximation reactions. The captured carbonyl compounds were eluted by methanol and the eluted solutions were analyzed by GC-MS for calculation of each compound concentration in the exhaled breath samples. Biostatistics was used to identify significant carbonyl compounds (defined as p value < 0.05) as markers of CPOVID-19 infection. A machine learning algorithm was implemented with the captured carbonyl compounds as input features for differentiation of COVID-19 positive from negative subjects. Results A total of more than 30 carbonyl compounds were detected in exhaled breath samples of all subjects. 10 features including 3 individual carbonyl compounds and 7 compound ratios show significant differences (p value <0.05) between COVID-19 positive and negative groups. The developed machine learning and artificial intelligence (AI) algorithms successfully separated COVOD-19 positive from negative with an accuracy of 95.4%, sensitivity of 96.5%, specificity of 93.7%, and AUROC=0.974. Conclusions The analysis of carbonyl compounds in exhaled breath by GC-MS has great potential for non-invasive detection of COVID-19. The method could be rapidly adapted for detection of other respiratory infectious diseases with a small sample size and data set for training of the machine learning and AI algorithms.

Evaluation of Efficacy and Safety of Different Doses of Eladis® in the Therapy of Cough Against Acute Respiratory Viral Infection

Aim. Justification of the optimal dosage regimen regarding the efficacy and safety of Eladis®, film-coated tablets, 10 mg (Valenta Pharm JSC, Russia) in comparison with placebo in patients with non-productive cough due to acute respiratory viral infection (ARVI). Material and methods. A double-blind placebo-controlled randomized multicenter study was conducted in which 141 patients with non-productive cough on the background of acute respiratory viral infection took part. The study participants were randomized into 4 groups. Patients from the first group took 1 tablet of Eladis® 2 times a day (daily dose of 20 mg); patients from the second group took 2 tablets of Eladis® 2 times a day (daily dose of 40 mg); patients from the third group took 4 tablets of Eladis® 2 times a day (daily dose of 80 mg). Patients in the fourth group received placebo tablets in quantities corresponding to the first three groups. For this purpose, 3 subgroups of 12 people were allocated within group 4. The duration of therapy was 7–14 days. The effectiveness of therapy was assessed based on monitoring the frequency of cough attacks, changes in values on the day and night cough scales, a digital rating scale (DRS), and the time to achieve clinical cure of cough and ARVI symptoms was also taken into account. The safety of the studied drug was assessed based on monitoring of vital signs, laboratory parameters, and electrocardiogram (ECG) data. The number and severity of adverse events (AEs) and serious adverse events (SAEs) were assessed. Results. Analysis of data on the primary endpoint (reduction of cough attack frequency by ;)50% by the 5th day relative to the 1st visit) showed the superiority of Eladis® over placebo at a daily dose of 80 mg (P=0.00003). At the same time, the proportion of patients who reached the primary endpoint by day 5 when receiving Eladis® at a dose of 80 mg per day was 71.43%, while in the combined placebo group it was 22.22%. Conclusion. Evaluation of various dosage regimens of Eladis® has shown that a daily dose of 80 mg is optimal for the treatment of non-productive cough in patients with ARVIs, as it provides the greatest effectiveness with a safety profile comparable to other studied doses.

B-207 Clinical Evaluation of ExiStation™ FA 96 RV for the detection of human respiratory viruses in human nasopharyngeal swab specimen

Abstract Background There has been growing demand for fully automated multiplex testing of respiratory viruses in molecular diagnostics following the COVID-19 pandemic. ExiStation™ FA 96 RV developed by BIONEER is a multiplex real-time RT-PCR assay. It is designed for the simultaneous detection and differentiation of SARS-CoV-2, Influenza A, Influenza B, and RSV RNA in human nasopharyngeal swab specimens from individuals showing signs and symptoms of respiratory viral infection. ExiStation™ FA 96 automates the entire process from RNA extraction to real-time RT-PCR for up to 96 samples at once within 100 minutes. Moreover, the system is equipped to decap sample tubes, eliminating the need for handling sample transport media. In this study, the clinical performance of the ExiStation™ FA 96 RV assay was evaluated using nasopharyngeal swab samples. Methods Nasopharyngeal swab samples, totaling 859 samples, are collected according to the procedures by the clinical institution in France and preserved in Virus transport media. Once anonymized and randomly allocated, the swab transport media tube, without capping procedure, are directly placed onto the ExiStation™ FA 96. Subsequently, both extraction and real-time RT-PCR are automatically processed. Clinical sensitivity, specificity, and agreement are analyzed by comparing results with confirmatory reagents SARS-CoV-2 RT-qPCR Reagent Kit, PKAmp™ Respiratory SARS-CoV-2 RT-PCR Panel Kit, and Bosphore SARS-CoV-2/Flu/RSV Panel Kit, as well as comparator reagent Allplex™ Respiratory Panel 1 and Allplex™ SARS-CoV-2 Assay. Results The comparison between confirmatory reagents and the ExiStation™ FA 96 RV resulted in a clinical sensitivity of at least 96.4% (164/164 for SARS-CoV-2, 64/65 for Influenza A, 74/75 for Influenza B, and 53/55 for RSV) and a clinical specificity of 100% (500/500 for all targets). When compared with the comparator reagent, the overall agreement and Cohen's kappa value were both determined to be above 99.1% and 0.989, respectively (664/664 for SARS-CoV-2, 564/565 for Influenza A, 573/575 for Influenza B, and 550/555 for RSV). Additionally, any discrepant samples identified in comparison with the comparator reagent were verified through sequencing analysis. Upon sequencing analysis on a total of 8 samples and aligning the confirmed results with the analysis content, no alterations observed in the analysis of clinical sensitivity and specificity. Conclusions The evaluation of the ExiStation™ FA 96 RV assay showed outstanding clinical performance in detecting four respiratory viruses, SARS-CoV-2, Influenza A, Influenza B, and RSV, with high sensitivity and specificity. This study supports that the ExiStation™ FA 96 RV assay is a reliable tool for simultaneous molecular diagnostics of various respiratory infections in clinical laboratories.