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Objective This study investigates the influence of timing of surgery among infants with congenital heart disease and active respiratory tract infections in a contemporary Western Canadian cohort. Methods This was a retrospective matched cohort study of infants aged 1 week to 6 months undergoing surgical repair of congenital heart disease between 2014 and 2017. Case patients had active respiratory tract infections preoperatively and were matched to control patients based on primary heart lesion. The primary outcome was time to extubation. Results We identified 20 cases (median age, 3.4 months [range, 2.4-4.3 months]) that were matched to 40 controls (1:2 ratio). In case patients, surgery occurred at a median of 1 day after the positive viral testing. There were no statistically significant differences between cases and controls in time to extubation (59 vs 34 hours [P = .12]), postoperative vasoactive scores at 24 hours (0 vs 0 [P = .53]), 48 hours (0 vs 0 [P = .23]), maximum vasoactive score in postoperative period (5 vs 5.5 [P = .54]), or time to hospital discharge (13 vs 12 days [P = .39]). Case patients had increased duration of total respiratory support (including noninvasive ventilation, 3.5 vs 2 days [P = .02]) and postoperative intensive care unit length of stay (5.5 vs 3 days [P = .01]). Conclusions Cardiac surgery on infants with congenital heart disease during an acute viral respiratory tract infection may yield a clinically relevant prolongation in time to extubation.

Background: Viral infections of the respiratory tract represent a major global health concern. Co-infection with bacteria may contribute to severe disease and increased mortality in patients. Nevertheless, viral-bacterial co-infection patterns and their clinical outcomes have not been well characterized to date. This study aimed to evaluate the clinical features and outcomes of patients with viral-bacterial respiratory tract co-infections. Methods: We included 19,361 patients with respiratory infection due to respiratory viruses [influenza A and B, respiratory syncytial virus (RSV), parainfluenza] and/or bacteria in four tertiary hospitals in Hong Kong from 2013 to 2017 using a large territory-wide healthcare database. All microbiological tests were conducted within 48 hours of hospital admission. Four etiological groups were included: (1) viral infection alone; (2) bacterial infection alone; (3) laboratory-confirmed viral-bacterial co-infection and (4) clinically suspected viral-bacterial co-infection who were tested positive for respiratory virus and negative for bacteria but had received at least four days of antibiotics. Clinical features and outcomes were recorded. The primary outcome was 30-day mortality. Secondary outcomes were intensive care unit (ICU) admission and length of hospital stay. Propensity score matching estimated by binary logistic regression was used to adjust for the potential bias that may affect the association between outcomes and covariates. Findings: Among 15,906 patients with respiratory viral infection, there were 8,451 (53.1%) clinically suspected and 1,087 (6.8%) laboratory-confirmed viral-bacterial co-infection. Among all the bacterial species, Haemophilus influenzae (226/1,087, 20.8%), Pseudomonas aeruginosa (163/1,087, 16.9%) and Streptococcus pneumoniae (123/1,087, 11.3%) were the three most common bacterial pathogens in the laboratory-confirmed co-infection group. Respiratory viruses co-infected with non-pneumococcal streptococci or methicillin-resistant Staphylococcus aureus was associated with the highest death rate [9/30 (30%) and 13/48 (27.1%), respectively] in this cohort. Compared with other infection groups, patients with laboratory-confirmed co-infection had higher ICU admission rate (p < 0.001) and mortality rate at 30 days (p = 0.012), and these results persisted after adjustment for potential confounders. Furthermore, patients with laboratory-confirmed co-infection had significantly higher mortality compared to patients with bacterial infection alone. Interpretation: In our cohort, bacterial co-infection is common in hospitalized patients with viral respiratory tract infection and is associated with higher ICU admission rate and mortality. Therefore, active surveillance for bacterial co-infection and early antibiotic treatment may be required to improve outcomes in patients with respiratory viral infection. Funding Information: Commissioned Programmes for Influenza Research, Health and Medical Research Fund (HMRF), FHB (Ref. No.: INF-CUHK-2); National Natural Science Foundation of China (81873560); Shenzhen Science and Technology Programme, Shenzhen Science and Technology Innovation Commission (JCYJ20180307150626228); Health and Medical Research Fund (18170092). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: Ethics approval was obtained from the Chinese University of Hong Kong.

Background: Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children ( 5 years) with and without history of severe prematurity (

Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophil-induced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment.

Background Respiratory infections are a major cause of morbidity and mortality worldwide. A high percentage of all respiratory tract infections are caused by RNA viruses. Real-time PCR is a highly sensitive method for the detection of respiratory viruses in clinical samples. A good RNA isolation protocol is of high importance, since RNA is more unstable than DNA and many clinical samples contain RNAses. Objectives To evaluate the performance of three different RNA extraction protocols for the extraction of respiratory viral RNA from sputum samples obtained from patients with the suspicion of a viral respiratory tract infection. Study design A total of 50 sputum samples, PCR positive for a respiratory RNA virus, were used for viral RNA isolation with the phenol/chloroform method, RTP ® DNA/RNA virus mini kit and the automated MagNa Pure LC (MPLC) extraction system. After isolation, real-time PCR was performed for the detection of viral RNA in the sputum samples. Results The MPLC extraction increased the detection probability from 82% (phenol/chloroform) and 86% (RTP ® DNA/RNA virus mini kit) to 94%. In 16% the RTP ® DNA/RNA virus mini kit resulted in lower C t values compared to the phenol/chloroform method, while in 32% the phenol/chloroform resulted in lower C t values. Conclusions The extraction of viral RNA performed with the MPLC extraction method was superior to the extraction with the RTP ® DNA/RNA virus mini kit and to the extraction with phenol/chloroform. In general, there was no difference in the detection of viral RNA between the phenol/chloroform extraction method and the RTP ® DNA/RNA virus mini kit.

Background Viral respiratory tract infections increase the risk of development and exacerbation of atopic disease. Previously, we demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of postviral atopic airway disease in mice. Objective We sought to determine whether human CD49d + PMNs are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in human subjects and mice. Methods Sixty subjects (5-50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swabs for viral PCR were performed at enrollment and during convalescence. The Sendai virus mouse model was used to investigate the phenotype and functional relevance of CD49d + PMNs. Results CD49d + PMN frequency was significantly higher in nasal lavage fluid during acute respiratory symptoms in all subjects (2.9% vs 1.0%, n = 42, P + PMNs represented a "proatopic" neutrophil subset that expressed cysteinyl leukotriene receptor 1 (CysLTR1) and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in the first days of a viral respiratory tract infection was sufficient to reduce accumulation of CD49d + PMNs in the lungs and development of postviral atopic airway disease. Similar to the mouse, human CD49d + PMNs isolated from nasal lavage fluid during a viral respiratory tract infection expressed CysLTR1. Conclusion CD49d and CysLTR1–coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease.

Acute cough is a major symptom of viral respiratory tract infection and causes excessive morbidity in human populations across the world. A wide variety of viruses play a role in the development of cough after acute infection and all of these manifest a similar clinical picture across different age groups. Despite the large disease burden surprisingly little is known about the mechanism of acute cough following viral infection. Both in vitro and in vivo experiments show that increased production of neuropeptides and leukotrienes mediate cough after viral infection, along with altered expression of neural receptors. Increased airway mucus production is also likely to play a significant role. This work is reviewed in this article. Following the recent development of a mouse model for rhinovirus infection and the establishment of experimental models of rhinovirus challenge in human subjects with both asthma and COPD the field is expanding to translate in vitro research into clinical studies and hopefully eventually into clinical practice. Developing a clearer understanding of the mechanisms underlying virus induced cough may lead to more specific and effective therapies.

Respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza viruses (PIV) and the influenza viruses cause severe lower respiratory tract disease in infants and children throughout the world. We discuss the recent discovery of the epidemiologic importance of the human metapneumoviruses, first reported in 2001. Experimental live-attenuated vaccines for each of these viruses are being developed for intranasal administration in the first weeks or months of life. The immunology of these infections in humans is poorly defined but many studies are ongoing. A significant obstacle to successful immunisation of infants against respiratory-virus-associated disease early in life may be the relatively poor immune response of very young infants to primary virus infection. This paper reviews the immune correlates of protection against disease caused by these viruses, immune responses of infants to naturally acquired infection or experimental infection with candidate vaccine viruses and the genetics of susceptibility to severe disease.

We prospectively studied 271 infants and children (2 months to 7 years of age) with acute otitis media (AOM) for viral and bacterial causes, outcome at the end of therapy, and frequency of recurrence within 1 month. Comprehensive virologic methods, including viral antigen detection, cell culture, and serologic studies, were used to diagnose viral infection of the respiratory tract, middle ear, or both. Evidence of viral infection was found in 46% (124/271) of patients with AOM. Sixty-six patients (24%) had virus or viral antigen in the middle ear fluid; 50 of these patients (76%) also had bacteria in middle ear fluid, and 16 (24%) had virus alone. More patients with AOM and combined bacterial and viral infection (51%) had persistent otitis (3 to 12 days after institution of antibiotic treatment), compared with those with only bacterial otitis (35%; p = 0.05) or patients with only viral infection (19%; p less than 0.01). Of patients with only viral infection, 4 of 10 with virus in middle ear fluid had persistent otitis, compared with none of 11 patients who had virus only in nasal wash specimens or whose viral infection was diagnosed only by serologic studies. Our data suggest that viruses interact with bacteria and that concurrent viral infection can significantly worsen the clinical course of bacterial AOM. The presence of virus in middle ear fluid may contribute to the pathogenesis and outcome of bacterial AOM. The mechanism of these interactions deserve further investigation.

No: 1717 Presentation at ESCV 2015: Poster 1 Automated testing for HSV meningitis using the Roche cobas® HSV 1 and 2 assay D. Fairley1,∗, J. Osiecki2, J. McKenna1, P. Coyle1 1 Belfast Health & Social Care Trust, United Kingdom 2 Roche Molecular Systems, United States Background: Infection with Herpes Simplex Virus (HSV) is common, with seropositivity in European countries of 50–80% reported for HSV-1 and 4–24% reported for HSV-2. HSV causes a spectrum of clinical disease in humans, ranging from relatively mild skin or genito-urinary infections, through to meningitis and life-threatening encephalitis, which can have mortality rates of more than 70%. Accurate and timely diagnosis of neurological HSV infection is critical, to facilitate early treatment with acyclovir. Molecular detection of HSV1/2 DNA in cerebrospinal fluid (CSF) is widely recognized as the gold standard method for diagnosis of the most severe neurological presentations. This study evaluated the diagnostic accuracy of the Roche cobas® HSV 1 and 2 assay for diagnosis of HSV meningitis, compared to published real-time TaqMan® assays for these targets [van Doornum et al., 2003. JCM 41(2):576–580]. Methods: Residual CSF specimens from patients with andwithout confirmed HSV meningitis were obtained from the Infectious Diseases BioArchive (Regional Virus Laboratory, Belfast). CSF specimens were added directly to MSwab primary sample collection tubes (Copan, Brescia, Italy) and processed using the automated Roche cobas® 4800 platform. The target CSF volume for testing was 200 l, althoughmany residual specimens weremuch smaller volumes (30–180 l). These specimens were included as being representative of the small volume CSF specimens that are often received for testing from neonates. Results: 17/17 (100%) of the PCR-positive specimens were also positive using the cobas® HSV 1 and 2 assay. 111/111 (100%) of the PCR-negative specimens were also negative using the cobas® assay, giving sensitivity of 100% and specificity of 100% relative to the in-house TaqMan® qPCR assay. Performance of the automated cobas 4800® platform will be discussed, and data from ongoing experiments to evaluate limits of detection using HSV-spiked CSF specimens will be presented. Conclusions: The Roche cobas® HSV1 and 2 assay is an effective and accurate method for diagnosis of HSV meningitis, even where CSF specimen volumes are limited. http://dx.doi.org/10.1016/j.jcv.2015.07.151

Viral respiratory tract infections, especially early in life, have been associated with a markedly increased risk of both allergic disease and asthma. Although much effort has been focused on understanding this risk, themechanisms linking a viral respiratory tract infection with atopic development still have not been fully elucidated. Hypothesizing that defects in the antiviral immune response might underlie the development of postviral atopic disease, Kaiko et al explored the effect of Toll-like receptor (TLR) 7 deficiency on disease development. In the human subject much of the viral risk of atopic disease has been associated with early-life severe respiratory syncytial virus (RSV) infection. RSV is a single-stranded RNA paramyxovirus that is a human, but not rodent, pathogen. The fact that RSV is not a natural rodent pathogen raises concerns over its use in some models, primarily because RSV infection in mice does not lead to clinically severe disease. Two other single-stranded RNA paramyxoviruses that are natural rodent pathogens and do induce severe clinical disease are Sendai virus (SeV) and pneumonia virus of mice (PVM). Genetically, PVM is more closely related to RSV than SeV, and it is this virus model that Kaiko et al studied in neonatal (1-week-old) mice. Although others have documented translation of viral infection into atopic disease with the PVM model, the current study specifically examined how a genetic loss of TLR7 affected disease development. TLR7 recognizes single-stranded RNA, and therefore mice deficient in TLR7 would be predicted to have a defect in single-stranded RNA viral clearance. Indeed, in this report the authors found that loss of TLR7 was associated with an increased viral load that translated into a more pronounced asthma-like response, as characterized by a TH2 cytokine milieu, airway hyperreactivity, and tissue eosinophilia. Whether this increase in atopic disease was a direct effect of the increased viral load/infection severity was not tested. With SeV, a direct correlation was seen between severity of the illness and the development of an asthma/atopic response, and therefore it is quite likely that a similar effect occurs with PVM.

— Sarah S. Long, MD Investigators from two neonatal intensive care units (NICUs) in Syracuse performed a prospective one-year study, testing nasopharyngeal specimens from prematurely born infants twice weekly using multiplex polymerase chain reaction (PCR) testing for respiratory viruses. No infant had clinical symptoms that led to virus testing, but a remarkable 52% of 50 infants studied had one or more virus detections. Infected infants had an average of 2.5 positive specimens. Some had a single virus detected repeatedly, others had different viruses detected sequentially or simultaneously. The mean time to first virus detection was 24 days (range 0 to 92 days). Viruses detected clustered during times of expected community activity of the virus. Virus detection was significantly associated with duration of intubation, use of supplemental oxygen, as well as the outcomes of length of hospital stay and diagnosis of bronchopulmonary dysplasia. Although no infant had clinically suspected viral respiratory tract infection, virus detection was associated with oxygen desaturation events and clinical deteriorations. Path analysis of the effects of viral infection on length of NICU stay after adjusting for possible confounding factors showed both significant direct effects of infection and indirect effects (ie, oxygen use and intubation). This type of study cannot address causal relationships between infection and outcomes, but the striking frequency of virus detection, the associated immediate negative events, and the possibility of important longer term negative outcomes makes this a sentinel study. Multiple hypotheses should be tested, including modes of acquisition of infection and methods of prevention. Article page 814<