Impact Of Respiratory Virus Infection Research Articles

P-679. Risk Factors Shared Among Common Respiratory Viruses

Abstract Background Upper respiratory infections affect patients of all ages, with severity influenced by demographics, comorbidities, and immunosuppression. Studies often determine risk factors associated with severe disease, but rarely are multiple upper respiratory pathogens compared within the same cohort. Using electronic health record (EHR) phenotyping of 267,031 participants with relevant EHR data enrolled in the National Institute of Health’s All of Us Research Program (All of Us), we identified and validated cohorts of participants, and revealed shared risk factors for severity among upper respiratory viruses. Methods We developed EHR phenotype algorithms for eight respiratory viruses using pathogen-specific billing codes, test results, and treatment-dose antivirals. We identified episodes of infection over 90-day periods and validated these using CDC national detection rates over the same period. We then used multivariable logistic regression to compare demographics and identify predictors of hospital admission, adjusting for age, sex, self-identified race and ethnicity, BMI, smoking status, and EHR record length. Results Scaled episode and testing counts paralleled CDC data, with expected seasonal trends observed for influenza, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, human metapneumovirus (hMPV), SARS-CoV-2, and human coronavirus (hCOV) (RSV, hCOV, influenza, and SARS-CoV-2 shown in Figure 1). Across viruses, hospital admission was associated with older age, male sex, underweight, severe obesity, self-identified Black race, and smoking (Table 1). Notably, significant predictors of admission included COPD, asthma, heart failure, ischemic heart disease, hypertension, diabetes, chronic kidney disease, and immunodeficiency, even after adjusting for confounding variables (Figure 2). Conclusion In this study we established and validated an EHR phenotyping algorithm, and demonstrated that clinical risk factors — particularly cardiopulmonary, metabolic, and immunological comorbidities — are associated with severe outcomes among multiple upper respiratory viruses. These results suggest that universal prevention interventions may mitigate the impact of respiratory viral infections in high-risk populations. Disclosures All Authors: No reported disclosures

Burden and Economic Impact of Respiratory Viral Infections in Adults Aged 60 and Older: A Focus on RSV

Background/Objectives: Respiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARIs) in adults aged 60 years and older, often leading to severe clinical outcomes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV compared to other ARIs, focusing on specific age groups, comorbidities, and demographic factors. Methods: A retrospective observational study was conducted using the electronic medical records of adults aged ≥60 years hospitalized for ARIs, including RSV, in Spain. Direct costs related to hospitalizations, intensive care unit (ICU) admissions, and treatments were analyzed. The study also assessed demographic, clinical, and comorbidity-related factors influencing the economic burden. Results: RSV infections resulted in significantly higher direct costs compared to other ARIs, particularly in patients aged 70–80 years. Comorbidities such as asthma and smoking history were associated with increased costs in RSV cases. Although ICU costs were comparable between groups, hospitalizations for RSV required longer stays and more intensive treatments, amplifying the overall economic burden. Differences in costs by age and sex highlighted the need for tailored clinical management strategies. Conclusions: RSV poses a substantial economic and clinical burden on adults aged 60 years and older, particularly in those with comorbidities. Preventive measures, such as vaccination, could reduce healthcare costs and improve outcomes in this vulnerable population. These findings support the inclusion of RSV vaccines in immunization programs, especially in aging populations like Spain, to alleviate healthcare pressures during peak respiratory disease seasons.

Impact of a Concurrent Respiratory Virus Infection on the Clinical Presentation and Response to Initial Treatment of Kawasaki Disease: A Single-Center Observational Study

Background: The impact of respiratory viral infections associated with Kawasaki Disease (KD) cases on KD’s clinical presentation and initial response to treatment has not been clearly determined. Objective: This study aimed to evaluate respiratory viral infections using FilmArray Respiratory Panel (FARP) testing and analyze the effect of the concurrent presence of pathogens on clinical presentations of KD. Methods: Between January 2021 and June 2023, we conducted a retrospective, single-center observational study of 105 Japanese children with KD. KD was diagnosed and treated according to RAISE study guidelines, and the cases’ clinical information was assessed. FARP testing was performed in 71 out of 105 KD cases with fever and/or respiratory symptoms. Results: In 38 (53.5%) out of 71 cases, at least one virus was detected. The FARP-positive cases tended to have a higher frequency of Kobayashi scores (K-scores) ≥ 5 than the negative cases (42.1% vs. 21.2%), and lower initial treatment failure (7.89% vs. 21.2%). The most common virus detected was rhino/enterovirus (RV/EV: 27 cases), followed by seven cases of respiratory syncytial virus (RSV). RV/EV-positive KD cases did not differ significantly in their clinical data or the frequency of K-scores ≥ 5, and RSV-positive cases showed significantly elevated liver enzyme (AST:59 U/L (43.5–150.5) vs. 35 U/L (27–41), ALT:40 U/L (28.5–244.5) vs. 18 U/L (14–27)) and CRP levels (12 mg/dL (7.3–14.2) vs. 6.5 mg/dL (4.1–8.5)), and an increased frequency of K-scores ≥ 5 (71.4% vs. 21.2%) compared to FARP-negative cases. KD cases that were also RSV-positive or RV/EV-positive showed favorable responses to initial treatments. Conclusions: Concurrent respiratory virus infection could affect the clinical manifestation and initial treatment response of KD.

Abstract IA007: Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs

Abstract Breast cancer is the second most common cancer globally. Most deaths from breast cancer are due to metastatic disease which often follows long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCC) is crucial for addressing metastatic progression. Infection with respiratory viruses (e.g. influenza or SARS-CoV-2) is common and triggers an inflammatory response locally and systemically. Here we show that influenza virus infection leads to loss of the pro-dormancy mesenchymal phenotype in breast DCC in the lung, causing DCC proliferation within days of infection, and a greater than 100-fold expansion of carcinoma cells into metastatic lesions within two weeks. Such DCC phenotypic change and expansion is interleukin-6 (IL-6)-dependent. We further show that CD4 T cells are required for the maintenance of pulmonary metastatic burden post-influenza virus infection, in part through attenuation of CD8 cell responses in the lungs. Single-cell RNA-seq analyses reveal DCC-dependent impairment of T-cell activation in the lungs of infected mice. SARS-CoV-2 infected mice also showed increased breast DCC expansion in lungs post-infection. Expanding our findings to human observational data, we observed that cancer survivors contracting a SARS-CoV-2 infection have substantially increased risks of lung metastatic progression and cancer-related death compared to cancer survivors who did not. These discoveries underscore the significant impact of respiratory viral infections on the resurgence of metastatic cancer, offering novel insights into the interconnection between infectious diseases and cancer metastasis. Citation Format: Shi B. Chia, Bryan J. Johnson, Junxiao Hu, Roel Vermeulen, Marc Chadeau-Hyam, Fernando Guntoro, Hugh Montgomery, Meher Boorgula, Varsha Sreekanth, Andrew Goodspeed, Bennett Davenport, Felipe Valenca-Pereira, Vadym Zaberezhnyy, Wolfgang E Schleicher, Dexiang Gao, Andreia N. Cadar, Michael Papanicolaou, Afshin Beheshti, Stephen B. Baylin, James Costello, Jenna M. Bartley, Thomas E. Morrison, Julio A. Aguirre-Ghiso, Mercedes Rincon, James DeGregori. Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA007.

Respiratory virus infections and adenovirus characteristics during acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease globally, characterized by obstructive ventilatory disorder under pulmonary function tests. Recent years have witnessed a yearly increase in the prevalence of COPD. To investigate the impact of respiratory virus infections on patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to perform sequencing typing and mutation analysis of viruses with high detection rate. A total of 1523 inpatients with AECOPD admitted to our hospital from April 1,2020 to March 30,2022 were collected and divided into two groups: the infected group (n= 532) and the non-infected group (n= 991). The related indexes between the two groups were collected and compared (including clinical characteristics and laboratory tests that blood cell count, PCT, CRP, adenovirus, respiratory syncytial virus, rhinovirus, influenza A virus, influenza B virus, etc.). In the infected group, the proportion of patients with palpitations (49.44% VS 8.07%, P< 0.001), lipid metabolism abnormalities (18.42% VS 39.96%, P< 0.001), heart failure (39.85% VS 29.87%, P< 0.001), disease duration (17.48 ± 7.47 VS 12.45 ± 11.43 d, P< 0.001), and poor prognosis (69.55% VS 17.15%, P< 0.001) were higher than those in the non-infected group; Adenovirus (ADV) accounted for 75.94% (404/532) of all infected viruses. 31 virus strains could be categorized into 16 ADV-C1, one ADV-C5, two ADV-B3, three ADV-B7, two ADV-D17, two ADV-D19, and five ADV-D27, which were similar to the serotypes reported in severe pneumonia. Furthermore, three strains of C1 adenovirus were found to be highly homologous to the original strain AF534906 by sequencing, and the phylogenetic trees of the three main structural genes were all on the same branch as the original strain. Base mutations and amino acid variants were found in each structural gene segment. In clinical data, it's found that patients with mutations are worse than those without mutations. Respiratory viruses are common in patients with poor prognosis of AECOPD, especially adenovirus, respiratory syncytial virus. Respiratory virus infections will lead to the deterioration of patients with AECOPD, accompanied by longer treatment cycles and poor prognosis.

Impact of respiratory viral infections on nasopharyngeal pneumococcal colonization dynamics in children.

Prevention of acute respiratory illnesses (ARI) in children is a global health priority, as these remain a leading cause of pediatric morbidity and mortality throughout the world. As new products and strategies to prevent respiratory infections caused by important pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, respiratory syncytial virus and pneumococcus are advancing, increasing evidence suggests that these and other respiratory viruses and pneumococci may exhibit interactions that are associated with altered colonization and disease dynamics. We aim to review recent data evaluating interactions between respiratory viruses and pneumococci in the upper respiratory tract and their potential impact on pneumococcal colonization patterns and disease outcomes. While interactions between influenza infection and subsequent increased susceptibility and transmissibility of colonizing pneumococci have been widely reported in the literature, emerging evidence suggests that human rhinovirus, SARS-CoV-2, and other viruses may also exhibit interactions with pneumococci and alter pneumococcal colonization patterns. Additionally, colonizing pneumococci may play a role in modifying outcomes associated with respiratory viral infections. Recent evidence suggests that vaccination with pneumococcal conjugate vaccines, and prevention of colonization with pneumococcal serotypes included in these vaccines, may be associated with reducing the risk of subsequent viral infection and the severity of the associated illnesses. Understanding the direction and dynamics of viral-pneumococcal interactions may elucidate the potential effects of existing and emerging viral and bacterial vaccines and other preventive strategies on the health impact of these important respiratory pathogens.

Impact of respiratory viral infections during pregnancy on the neurological outcomes of the newborn: current knowledge.

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring's neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions.

Severe Acute Respiratory Infection-Preparedness: Protocol for a Multicenter Prospective Cohort Study of Viral Respiratory Infections.

Prospective cohort study. Multicenter cohort of patients admitted to an acute care ward or ICU from at least 15 hospitals representing diverse geographic regions across the United States. Patients with SARI caused by infection with respiratory viruses that can cause outbreaks, epidemics, and pandemics. None. Measurements include patient demographics, signs, symptoms, and medications; microbiology, imaging, and associated tests; mechanical ventilation, hospital procedures, and other interventions; and clinical outcomes and hospital stress, with specimens collected on days 0, 3, and 7-14 after enrollment and at discharge. The primary outcome measure is the number of consecutive days alive and free of mechanical ventilation (VFD) in the first 30 days after hospital admission. Important secondary outcomes include organ failure-free days before acute kidney injury, shock, hepatic failure, disseminated intravascular coagulation, 28-day mortality, adaptive immunity, as well as immunologic and microbiologic outcomes. SARI-Preparedness is a multicenter study under the collaboration of the Society of Critical Care Medicine Discovery, Resilience Intelligence Network, and National Emerging Special Pathogen Training and Education Center, which seeks to improve understanding of prognostic factors associated with worse outcomes and increased resource utilization. This can lead to interventions to mitigate the clinical impact of respiratory virus infections associated with SARI.

510 Prevalence and clinical impact of respiratory viral infections in the Standardized Treatment of Pulmonary Exacerbations 2 Study

510 Prevalence and clinical impact of respiratory viral infections in the Standardized Treatment of Pulmonary Exacerbations 2 Study

Characteristics of patients with viral infections of the lower respiratory tract: A retrospective study.

While the impact of respiratory virus infections has been well researched in some respiratory diseases, no clinical studies have discussed the subject of who would be more likely to develop respiratory virus infections among patients with various respiratory illnesses who come from different backgrounds. This study aimed to identify respiratory diseases that are frequently associated with respiratory virus infections along with the characteristics of patients who develop such infections in clinical settings. Tested specimens were obtained from the lower respiratory tract by bronchoscopy to provide more accurate data. Data of bronchoscopies at Ryukyu University Hospital between August 2012 and September 2016 were reviewed, and patients who underwent multiplex polymerase chain reaction (PCR) tests for detecting respiratory viruses in bronchoscopy specimens were retrospectively recruited for descriptive statistics. Differences among patients’ primary pulmonary diseases and backgrounds were compared between the PCR-positive and -negative patients, and multivariate statistical analysis was performed to analyze factors associated with a positive PCR test result. Overall, 756 bronchoscopies were performed during the study period and PCR tests were performed for 177 patients. Of them, 27 tested positive for respiratory viruses, mainly parainfluenza virus and rhinovirus, and out of those, 7 were hospitalized for >1 month. Overall, all patients did not experience typical upper respiratory infection symptoms. In positive patients, 13 and 7 had diagnoses of interstitial lung disease and bacterial pneumonia, respectively. The diagnoses of 3 bacterial pneumonia cases were changed to viral pneumonia after receiving their PCR-positive tests. Respiratory virus infections were confirmed in 14 patients on immunosuppressant therapy and 4 on maintenance dialysis. Multivariate analysis revealed that immunosuppressant therapy and maintenance dialysis were independently associated with respiratory virus infections. Viruses were commonly detected in patients with interstitial lung diseases and bacterial pneumonia, while few patients were diagnosed with pure viral pneumonia. These illnesses were considered to be induced by respiratory infections. Immunosuppressant therapy and maintenance dialysis were associated with respiratory virus infections. Multiplex PCR testing is an essential diagnostic tool for respiratory virus infections in immunocompromised patients.

Impact of respiratory viral infections on mortality and critical illness among hospitalized patients with chronic obstructive pulmonary disease.

Seasonal respiratory viral infections are associated with exacerbations and morbidity among patients with COPD. The real-world clinical outcomes associated with seasonal viral infections are less well established among hospitalized patients. To estimate the association between seasonal respiratory viral infections, 30-day mortality, and intensive care unit (ICU) admission among hospitalized COPD patients. We conducted an analysis of a national prospective multicenter cohort of COPD patients hospitalized with acute respiratory illness during winter seasons (2011-2015) in Canada. Nasopharyngeal swabs were performed on all patients at the onset of hospital admission for diagnosis of viral infection. Primary outcomes were 30-day mortality and ICU admissions. Secondary outcomes included invasive/non-invasive ventilation use. Among 3931 hospitalized patients with COPD, 28.5% (1122/3931) were diagnosed with seasonal respiratory viral infection. Viral infection was associated with increased admission to ICU (OR 1.5, 95% CI 1.2-1.9) and need for mechanical ventilation (OR 1.9, 95% CI 1.4-2.5), but was not associated with mortality (OR 1.1, 95% CI 0.8-1.4). Patients with respiratory syncytial virus (RSV) were equally likely to require ICU admission (OR 1.09, 95% CI 0.67-1.78), and more likely to need non-invasive ventilation (OR 3.1; 95% CI 1.8-5.1) compared to patients with influenza. Our results suggest COPD patients requiring hospitalization for respiratory symptoms should routinely receive viral testing at admission, especially for RSV and influenza, to inform prognosis, clinical management, and infection control practices during winter seasons. Patients with COPD will be an important target population for newly developed RSV therapeutics. ClinicalTrials.gov ID: NCT01517191.

First person – Nannan Gao

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Nannan Gao is first author on ‘ Respiratory syncytial virus disrupts the airway epithelial barrier by decreasing cortactin and destabilizing F-actin’, published in JCS. Nannan is a postdoctoral fellow in the lab of Fariba Rezaee, at the Cleveland Clinic, Cleveland, OH, investigating the impact of respiratory viral infection and environmental factors on airway epithelial barrier.

Influenza A H1N1 Induced Disturbance of the Respiratory and Fecal Microbiome of German Landrace Pigs - a Multi-Omics Characterization.

ABSTRACTSeasonal influenza outbreaks represent a large burden for the health care system as well as the economy. While the role of the microbiome has been elucidated in the context of various diseases, the impact of respiratory viral infections on the human microbiome is largely unknown. In this study, swine was used as an animal model to characterize the temporal dynamics of the respiratory and gastrointestinal microbiome in response to an influenza A virus (IAV) infection. A multi-omics approach was applied on fecal samples to identify alterations in microbiome composition and function during IAV infection. We observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, increased abundances of Prevotellaceae were detected, while Clostridiaceae and Lachnospiraceae decreased. Moreover, our metaproteomics data indicated that the functional composition of the microbiome was heavily affected by the influenza infection. For instance, we identified decreased amounts of flagellin, correlating with reduced abundances of Lachnospiraceae and Clostridiaceae, possibly indicating involvement of a direct immune response toward flagellated Clostridia during IAV infection. Furthermore, enzymes involved in short-chain fatty acid (SCFA) synthesis were identified in higher abundances, while metabolome analyses revealed rather stable concentrations of SCFAs. In addition, 16S rRNA gene sequencing was used to characterize effects on the composition and natural development of the upper respiratory tract microbiome. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae in the upper respiratory tract. Surprisingly, temporal development of the respiratory microbiome structure was not affected.IMPORTANCE Here, we used swine as a biomedical model to elucidate the impact of influenza A H1N1 infection on structure and function of the respiratory and gastrointestinal tract microbiome by employing a multi-omics analytical approach. To our knowledge, this is the first study to investigate the temporal development of the porcine microbiome and to provide insights into the functional capacity of the gastrointestinal microbiome during influenza A virus infection.

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia.

Background: The impact of respiratory virus infection in patients diagnosed with ataxia-telangiectasia (A-T) has not been well studied. Methods: A prospective case control study was performed at a National Reference Unit for Primary Immunodeficiency in Spain (from November 2018 to July 2019), including patients younger than 20 years. Symptom questionnaires and nasopharyngeal swabs from multiple respiratory viruses’ polymerase chain reaction were collected monthly, and between visits in case of symptoms. Results: Twenty-two individuals were included (11 patients; 11 controls); 164 samples were obtained (81 patients; 84 controls). Patients presented respiratory symptoms more frequently compared with controls (26.5% vs. 3.5%; p < 0.01). Viral detection was observed in 23 (27.3%) episodes in patients and in 15 (17.8%) episodes in controls (p = 0.1). Rhinovirus was the most frequent virus in patients and controls (60% and 53.3%, respectively). Episodes with positive viral detection had associated symptoms in 54% of patients and 18% of controls (p = 0.07). However, patients with A-T presented a similar rate of symptoms during episodes with positive and negative viral detection (26% vs. 27%). The median points given for each questionnaire during symptomatic episodes with negative viral detection were 13/23 points, and during symptomatic positive detection, 7.5/23 points (p = 0.1). In the control group, all but two were asymptomatic during positive viral episodes (score: 2/23 and 3/23 points). Symptomatic episodes, with either positive or negative viral detection, were associated with lower IgA and higher IgM titers and higher CD8+ counts (p < 0.05), particularly when these episodes were moderate/severe. Conclusions: Patients with A-T more frequently present symptomatic viral infections than controls, especially those with lower IgA and higher IgM titers and higher CD8+ counts.

Electrospun Nanofiber Mats for Filtering Applications-Technology, Structure and Materials.

Air pollution is one of the biggest health and environmental problems in the world and a huge threat to human health on a global scale. Due to the great impact of respiratory viral infections, chronic obstructive pulmonary disease, lung cancer, asthma, bronchitis, emphysema, lung disease, and heart disease, respiratory allergies are increasing significantly every year. Because of the special properties of electrospun nanofiber mats, e.g., large surface-to-volume ratio and low basis weight, uniform size, and nanoporous structure, nanofiber mats are the preferred choice for use in large-scale air filtration applications. In this review, we summarize the significant studies on electrospun nanofiber mats for filtration applications, present the electrospinning technology, show the structure and mechanism of air filtration. In addition, an overview of current air filtration materials derived from bio- and synthetic polymers and blends is provided. Apart from this, the use of biopolymers in filtration applications is still relatively new and this field is still under-researched. The application areas of air filtration materials are discussed here and future prospects are summarized in conclusion. In order to develop new effective filtration materials, it is necessary to understand the interaction between technology, materials, and filtration mechanisms, and this study was intended to contribute to this effort.

Seasonal variation of respiratory viral infections: a comparative study between children with cancer undergoing chemotherapy and children without cancer

Respiratory viral infections (RVIs) affect children year-round, with seasonal-specific patterns. Pediatric oncology patients are uniquely vulnerable to infection, but whether this predisposes them to different patterns of RVIs than healthy children is unknown. There is also limited data on the impact of RVIs on cancer patients. We conducted a retrospective study of children ages 1–21 with cancer presenting to the clinic and emergency department (ED) and a randomly selected subset of patients without cancer presenting to the ED who had positive nasopharyngeal viral polymerase chain reactions at our institution from 2014 to 2019. Sixty-seven cancer patients (206 RVI episodes) and 225 pediatric non-cancer patients (237 RVI episodes) were included. Human rhino/enterovirus (HRE) was the most common infection in both groups in the spring, summer, and fall. In the winter, the most common RVI was influenza in cancer patients verses respiratory syncytial virus in non-cancer patients. On age-adjusted analysis, the likelihood of detecting coronavirus in the winter, HRE in the spring and fall, and parainfluenza in the summer was significantly greater in cancer patients (OR = 2.60, 2.52, 5.73, 3.59 respectively). Among cancer RVI episodes, 50% received parenteral antibiotics, 22% were severely neutropenic, 22% had chemotherapy delays for a median of six days, 16% were hospitalized, and 6% received intravenous immunoglobulin. We conclude that there are differences in the seasonal patterns of RVIs between children with and without cancer. RVIs also cause significant morbidity in children with cancer.

TLR2-mediated activation of innate responses in the upper airways confers antiviral protection of the lungs.

The impact of respiratory virus infections on global health is felt not just during a pandemic, but endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen-independent innate immunity in the upper airways can prevent the spread of respiratory virus infection to the vulnerable lower airways. Activation of TLR2, when restricted to the nasal turbinates, resulted in prompt induction of innate immune–driven antiviral responses through action of cytokines, chemokines, and cellular activity in the upper but not the lower airways. We have defined how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to 7 days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

1509. Impact of Respiratory Viral Infection on Outcomes of Congenital Heart Repair Surgery

BackgroundRespiratory viral infections are common in the pediatric population and can range from mild to life-threatening. Given the risk factors that accompany these infections, some pediatric cardiothoracic surgeons in the United States avoid performing surgery for patients with congenital heart disease when there is a possibility of concurrent viral respiratory illness. Studies in this patient population have been limited either by small study populations, or a study focus that is too narrow. The impact of respiratory infections on patient outcomes based on previous literature is also unclear.MethodsThis retrospective chart review study aimed to compare outcomes after congenital heart repair surgery in patients with positive respiratory viral testing to those with negative testing over a five-year period, to determine if there are significant differences related to post-operative hospital course or morbidity.Patient Inclusion Flowchart ResultsThis study included 120 patients, of whom 43 tested positive for respiratory viruses and 77 tested negative. Patients were additionally divided based on the presence or absence of symptoms of respiratory infection, with 79 patients demonstrating respiratory symptoms and 41 who did not. Results demonstrate that negative respiratory viral testing is associated with a significant increase in post-operative ICU LOS (p = 0.01), hospital LOS (p < 0.01), and duration of post-operative respiratory support (p < 0.01), compared to positive testing. Additionally, an absence of respiratory symptoms at the time of testing was associated with a significant increase in post-operative ICU LOS (p = 0.01) and hospital LOS (p < 0.01), compared to patients who were symptomatic.Outcomes by Positive vs. Negative FilmArray Outcomes by Symptomatic vs. Asymptomatic ConclusionThese results suggest that negative respiratory viral testing or lack of respiratory infectious symptoms should not be a reassuring factor in patients scheduled for repair of congenital heart disease, and positive testing does not appear to result in worse outcomes after surgery. Based on this data, we would recommend that respiratory viral testing should not be a routine component of preoperative planning for patients scheduled to undergo congenital heart repair surgery, which would reduce the burdens of unnecessary testing and delays in definitive heart repair.Disclosures All Authors: No reported disclosures

Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium

BackgroundViral respiratory tract infections, such as influenza A virus (IAV), are common and life-threatening illnesses worldwide. The mechanisms by which viruses are removed from the respiratory tract are indispensable for airway host defense. Mucociliary clearance is an airway defense mechanism that removes pathogens from the respiratory tract. The coordination and modulation of the ciliary beating of airway epithelial cells play key roles in maintaining effective mucociliary clearance. However, the impact of respiratory virus infection on ciliary activity and mucociliary clearance remains unclear.MethodsTracheal samples were taken from wild-type (WT) and Toll-like receptor 3 (TLR3)-knockout (KO) mice. Transient organ culture of murine trachea was performed in the presence or absence of IAV, polyI:C, a synthetic TLR3 ligand, and/or reagents. Subsequently, cilia-driven flow and ciliary motility were analyzed. To evaluate cilia-driven flow, red fluorescent beads were loaded into culture media and movements of the beads onto the tracheal surface were observed using a fluorescence microscope. To evaluate ciliary motility, cilia tips were labeled with Indian ink diluted with culture medium. The motility of ink-labeled cilia tips was recorded by high-speed cameras.ResultsShort-term IAV infection significantly increased cilia-driven flow and ciliary beat frequency (CBF) compared with the control level in WT culture. Whereas IAV infection did not elicit any increases of cilia-driven flow and CBF in TLR3-KO culture, indicating that TLR3 was essential to elicit an increase of cilia-driven flow and CBF in response to IAV infection. TLR3 activation by polyI:C readily induced adenosine triphosphate (ATP) release from the trachea and increases of cilia-driven flow and CBF in WT culture, but not in TLR3-KO culture. Moreover, blockade of purinergic P2 receptors (P2Rs) signaling using P2R antagonist, suramin, suppressed polyI:C-mediated increases of cilia-driven flow and CBF, indicating that TLR3-mediated ciliary activation depended on released extracellular ATP and the autocrine ATP-P2R loop.ConclusionsIAV infection readily increases ciliary activity and cilia-driven flow via TLR3 activation in the airway epithelium, thereby hastening mucociliary clearance and “sweeping” viruses from the airway as an initial host defense response. Mechanically, extracellular ATP release in response to TLR3 activation promotes ciliary activity through autocrine ATP-P2R loop.

Epidemiology and clinical impact of viral, atypical, and fungal respiratory pathogens in symptomatic immunocompromised patients: a two-center study using a multi-parameter customized respiratory Taqman® array card.

The prevalence of respiratory viruses in immunocompromised adult patients and the association with clinical outcomes is still underexplored. Our goal was to assess the epidemiology and the potential clinical impact of respiratory viral infections in a high-risk patient population. Two large hospitals performed a respiratory Taqman array card (TAC), targeting 24 viruses, 8 bacteria, and 2 fungi simultaneously, on 435 samples from 397 symptomatic immunocompromised patients. Clinical details were collected retrospectively using a structured case report form. An overall positivity rate of 68% was found (51% mono- and 17% co-infections). Pathogen distribution was as follows: influenza A (20.7%), rhinoviruses (15.2%), coronaviruses (7.8%), Pneumocystis jirovecii (7.4%), RSV (7.1%), and CMV (6.0%) were the most frequently encountered, followed by HSV (5.5%), hMPV (4.4%), parainfluenza viruses (3.9%), influenza B (3.7%), and Aspergillus species (3.7%). Other pathogens were not detected or detected only in ≤ 1% of samples. Hospital and ICU admission rates were 84% and 11%, respectively. The presence of a pathogen was strongly associated with higher need for supplemental oxygen (p = 0.001), but it had no impact on ICU admission, mechanical ventilation requirement, antibacterial therapy, or mortality. In conclusion, our study described the epidemiology of respiratory pathogens in a large group of symptomatic immunocompromised patients and provides evidence of a relationship between pathogen detection and the need for supplemental oxygen. This association was still found after the exclusion of the results positive for influenza viruses, suggesting that non-influenza viruses contribute to severe respiratory illness in patients with compromised immunity.