Clinical features of parainfluenza infections among young children hospitalized for acute respiratory illness in Amman, Jordan.

BACKGROUND: Parainfluenza virus (PIV) is a leading cause of acute respiratory illness (ARI) in children. However, few studies have characterized the clinical features and outcomes associated with PIV infections among young children in the Middle East. METHODS: We conducted hospital-based surveillance for ARI among children < 2 years of age in a large referral hospital in Amman, Jordan. We systematically collected clinical data and respiratory specimens for pathogen detection using reverse transcription polymerase chain reaction. We compared clinical features of PIV-associated ARI among individual serotypes 1, 2, 3, and 4 and among PIV infections compared with other viral ARI and ARI with no virus detected. We also compared the odds of supplemental oxygen use using logistic regression. RESULTS: PIV was detected in 221/3168 (7.0%) children hospitalized with ARI. PIV-3 was the most commonly detected serotype (125/221; 57%). Individual clinical features of PIV infections varied little by individual serotype, although admission diagnosis of 'croup' was only associated with PIV-1 and PIV-2. Children with PIV-associated ARI had lower frequency of cough (71% vs 83%; p < 0.001) and wheezing (53% vs 60% p < 0.001) than children with ARI associated with other viruses. We did not find a significant difference in supplemental oxygen use between children with PIV-associated infections (adjusted odds ratio [aOR] 1.12, 95% CI 0.66-1.89, p = 0.68) and infections in which no virus was detected. CONCLUSIONS: PIV is frequently associated with ARI requiring hospitalization in young Jordanian children. Substantial overlap in clinical features may preclude distinguishing PIV infections from other viral infections at presentation.

Co-infection with SARS-CoV-2 and parainfluenza virus in a hemodialysis patient: A case report.

BACKGROUND: In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread to many countries. Limited data are available for hemodialysis patients with COVID-19. CASE PRESENTATION: We report a 66-year-old man with confirmed COVID-19 and parainfluenza virus infection in Wuhan. We describe the clinical characteristics, radiological findings, and treatment of the hemodialysis patient, including the patient's initial pneumonia at presentation with progression to acute respiratory distress syndrome (ARDS). DISCUSSION AND CONCLUSION: Our case underscores the possibility of SARS-CoV-2 co-infection with other pathogens in hemodialysis patients and the importance of early identification of COVID-19.

Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.

Broadly neutralizing antibodies reactive against most and even all variants of the same viral species have been described for influenza and HIV-1 (ref. 1). However, whether a neutralizing antibody could have the breadth of range to target different viral species was unknown. Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are common pathogens that cause severe disease in premature newborns, hospitalized children and immune-compromised patients, and play a role in asthma exacerbations. Although antisera generated against either HRSV or HMPV are not cross-neutralizing, we speculated that, because of the repeated exposure to these viruses, cross-neutralizing antibodies may be selected in some individuals. Here we describe a human monoclonal antibody (MPE8) that potently cross-neutralizes HRSV and HMPV as well as two animal paramyxoviruses: bovine RSV (BRSV) and pneumonia virus of mice (PVM). In its germline configuration, MPE8 is HRSV-specific and its breadth is achieved by somatic mutations in the light chain variable region. MPE8 did not result in the selection of viral escape mutants that evaded antibody targeting and showed potent prophylactic efficacy in animal models of HRSV and HMPV infection, as well as prophylactic and therapeutic efficacy in the more relevant model of lethal PVM infection. The core epitope of MPE8 was mapped on two highly conserved anti-parallel ß-strands on the pre-fusion viral F protein, which are rearranged in the post-fusion F protein conformation. Twenty-six out of the thirty HRSV-specific neutralizing antibodies isolated were also found to be specific for the pre-fusion F protein. Taken together, these results indicate that MPE8 might be used for the prophylaxis and therapy of severe HRSV and HMPV infections and identify the pre-fusion F protein as a candidate HRSV vaccine.

Prevalence, clinical outcomes and rainfall association of acute respiratory infection by human metapneumovirus in children in Bogotá, Colombia.

BACKGROUND: Acute respiratory infections (ARIs) are one of the main causes of morbidity and mortality in children. Viruses are the main etiological agents, and their behavior tends to be seasonal and vary by geographical location. Human metapneumovirus (HMPV) has recently been described as a cause of severe acute respiratory infection and its prevalence and clinical behavior in children at moderate altitudes is unknown. METHODS: A cross-sectional study was carried out on patients seen at a university hospital in Bogotá, Colombia between October 2015 and December 2017 in a city at a moderate altitude above sea level. Children with acute respiratory infections who had had a multiplex RT-PCR assay were selected. The prevalence of HMPV infection, its clinical outcomes and its relationship to rainfall were evaluated. RESULTS: Out of a total of 14,760 discharged patients, multiplex RT-PCR was performed on 502 and a virus was detected in 420 children with acute respiratory infection (ARI). The study group had a median age of 21 months (IQR 7-60), with similar proportion of males and females (56.4 and 43.6% respectively) and 5.2% (CI 95 3.3-7.8%) prevalence of HMPV infection. The group with HMPV infection showed a greater frequency of viral coinfection (22.7% vs 14% P = 0.03) compared with ARI caused by other viruses. The rate of bacterial coinfection (P = 0.31), presence of comorbidities (p = 0.75), length of hospital stay (P = 0.42), need for mechanical ventilation (P = 0.75) and mortality (P = 0.22) were similar for HMPV and other viral infections. A moderate correlation was established between HMPV infection and rainfall peaks (Spearman's Rho 0.44 p = 0.02). CONCLUSIONS: Human metapneumovirus was the fifth most frequently isolated virus in children with ARI, had similar clinical behavior and severity to other viruses but a higher rate of viral coinfection. Its peaks seem to correlate to rainy seasons.

Virus detection in critically ill children with acute respiratory disease: a new profile in view of new technology.

AIM: To describe the epidemiology of critically ill children admitted to a paediatric intensive care unit (PICU) with acute respiratory disease. The association with intubation was analysed for the three most prevalent viruses and in those with and without viral co-infection. METHODS: Patients admitted to the PICU (2004-2014) with acute respiratory disease were included. Analyses were performed utilising each respiratory viral infection or multiple viral infections as an exposure. RESULTS: There were 1766 admissions with acute respiratory disease of which 1372 had respiratory virus testing and 748 had one or more viruses detected. The risk of intubation before or during the PICU stay was higher if parainfluenza virus was detected compared to respiratory syncytial virus (RSV) (OR: 2.20; 95% CI: 1.06-4.56). Sixty-three admissions had two or more viruses detected, and the combination of RSV and Rhinovirus/enterovirus was the most common. No significant difference was observed in the risk of intubation between patients with multiple and single viral infections. CONCLUSION: Higher risk of intubation was found in patients with parainfluenza as compared to RSV. The risk of intubation comparing parainfluenza virus to other viruses and for patients with multiple versus single virus needs to be further studied.

Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy.

Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.

A broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus.

BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection, with significant morbidity and mortality. No licensed vaccines or therapeutic agents exist. Monoclonal antibodies (mAbs) are effective at preventing other infectious diseases and could be used against HMPV in high-risk hosts. METHODS: In vitro assays were performed to assess the neutralizing activity and affinity kinetics of human mAb 54G10. A new mouse model was developed to assess prophylactic and therapeutic efficacy in vivo. The epitope of 54G10 was identified by generating mAb-resistant mutants (MARMs). RESULTS: At low concentrations, 54G10 neutralized all 4 subgroups of HMPV in vitro and had subnanomolar affinity for the fusion protein. DBA/2 mice were permissive for all 4 HMPV subgroups, and 54G10 was effective both prophylactically and therapeutically against HMPV in vivo. Sequencing of HMPV MARMs identified the 54G10 epitope, which was similar to an antigenic site on respiratory syncytial virus (RSV). 54G10 also exhibited in vitro neutralizing activity and in vivo protective and therapeutic efficacy against RSV. CONCLUSIONS: Human mAb 54G10 has broad neutralizing activity against HMPV and could have prophylactic and therapeutic utility clinically. The conserved epitope could represent a structural vaccine target for HMPV and RSV.

One-Year Prospective Study of Community Acquired Influenza and Parainfluenza Viral Infections in Hospitalized Egyptian Children with Malignancy: Single Center Experience.

BACKGROUND: Respiratory viruses are widespread in the community and easily transmitted to immunocompromised patients. AIMS: Assess the prevalence of community-acquired respiratory viral infections among children with cancer presenting with clinical picture suggestive of lower respiratory tract infections (LRTIs), and evaluate its risk factors and prognosis. METHODS: Over a year, 90 hospitalized children with malignancy and LRTIs recruited, subjected to clinical assessment, investigated through hematology panel, blood culture, chest x-ray, CT chest and PCR for influenza A and B, parainfluenza (PIV) types 1 and 3 viruses, and respiratory syncytial virus (RSV), and prospectively followed up for the clinical outcome. RESULTS: Viral pathogens were identified in 34 patients (37.7%), with a seasonal peak from April to May. The most frequently detected virus was influenza virus [type A (16 cases; 47%), type B (4 cases; 12%)] followed by parainfluenza virus [PIV1 (9 cases; 26%), PIV3 (3 cases; 15%)], and none had RSV. Bacteria were identified in 26 patients, fungi in four, mixed infections [bacterial/viral and bacterial/fungal] in 13, and 36 cases had unidentified etiology. The majority of patients with influenza and parainfluenza infections had hematological malignancy, presented with fever, and had mild self-limited respiratory illness. Five patients with mixed viral and bacterial infection had severe symptoms necessitating ICU admission. Six patients died from infection-related sequelae; two had mixed PIV and Staphylococcal infections. CONCLUSIONS: Community acquired influenza and parainfluenza infections are common in pediatrics patients with malignancy, either as isolated or mixed viral/bacterial infections. Clinical suspicion is essential as hematological and radiological manifestations are nonspecific. Rapid diagnosis and management are mandatory to improve patients' outcome.

Treatment of severe human metapneumovirus (hMPV) pneumonia in an immunocompromised child with oral ribavirin and IVIG.

BACKGROUND: The clinical manifestations of human metapneumovirus (hMPV) infection resemble those of respiratory syncytial virus with the most severe disease occurring in infants, the elderly, chronically ill, and immunocompromised hosts. OBSERVATION: We present a case of a 2-year-old girl undergoing intensive chemotherapy for Burkitt lymphoma who developed severe hMPV pneumonia. Rapid and complete recovery was observed after treatment with oral ribavirin and intravenous immunoglobulin. CONCLUSION: As hMPV can cause severe pneumonia in immunocompromised patients and due to the reports of effective treatment with ribavirin, clinical studies to elucidate the role of ribavirin in treatment of hMPV pneumonia may be needed.

A multicenter outcomes analysis of children with severe viral respiratory infection due to human metapneumovirus.

OBJECTIVE: To investigate the impact of human metapneumovirus on morbidity and mortality outcomes in children with severe viral respiratory infection. DESIGN: Retrospective cohort study. SETTING: ICU, either PICU or cardiac ICU, at three urban academic tertiary care children's hospitals. PATIENTS: All patients admitted to an ICU with laboratory-confirmed human metapneumovirus infection between January 2010 and June 2011. INTERVENTIONS: We captured demographic and clinical data and analyzed associated morbidity and mortality outcomes. MEASUREMENTS AND MAIN RESULTS: There were 111 patients with laboratory-confirmed human metapneumovirus admitted to an ICU at one of the three participating institutions during the period of study. The median hospital length of stay was 7 days (interquartile range 4-18 days) and median ICU length of stay was 4 days (interquartile range 1-10 days). Ten patients (9%) did not survive to discharge. Predisposing factors associated with increased mortality included female gender (p = 0.002), presence of a chronic medical condition (p = 0.04), and hospital acquisition of human metapneumovirus infection (p = 0.006). Adjusting for female gender, chronic medical conditions, hospital acquisition of infection and severity of illness score, logistic regression analysis demonstrated that female gender, hospital acquisition of infection, and chronic medical conditions each independently increased the odds of mortality (odds ratios 14.8, 10.7, and 12.7, respectively). CONCLUSIONS: Analysis of our results suggests that there is substantial morbidity and mortality associated with severe viral respiratory infection due to human metapneumovirus in children. Female gender, hospital acquisition of human metapneumovirus infection, and presence of chronic medical conditions each independently increases mortality. The burden of illness from human metapneumovirus on the ICU in terms of resource utilization may be considerable.

Clinical factors associated with extended hospitalization in pediatric patients ≥3 years of age with respiratory syncytial virus or human metapneumovirus infection: A Japanese single-center, retrospective study.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections are common in children worldwide. However, the clinical factors related to extended hospitalization in Japanese patients aged ≥3 years remain elusive. We aimed to elucidate the clinical risk factors contributing to hospital stays ≥7 days in patients with RSV and hMPV infections. Patients ≥3 years of age who were hospitalized due to RSV or hMPV infection between 2014 to 2020 were included. Twenty-one RSV- and 27 hMPV-infected patients were enrolled. Patients were divided into 2 groups: hospitalization for ≥ and <7 days. Univariate and multivariate analyses determined the clinical risk factors contributing to hospital stay ≥7 days. The RSV- and hMPV-infected patients had similar clinical characteristics. The clinical risk factors contributing to extended hospitalization were analyzed in the 48 infected patients of the 2 groups. The presence of prophylactic antibiotics usage, co-bacterial colonization, and underlying diseases were extracted by univariate analysis (P < .05). In multivariate analysis, underlying diseases were determined as an independent clinical risk factor (odds ratio 8.09, P = .005). Underlying diseases contributed to extended hospitalization in RSV- or hMPV-infected patients ≥3 years of age.

Azithromycin therapy in hospitalized infants with acute bronchiolitis is not associated with better clinical outcomes: a randomized, double-blinded, and placebo-controlled clinical trial.

OBJECTIVE: To test the hypothesis that azithromycin reduces the length of hospitalization and oxygen requirement in infants with acute viral bronchiolitis (AB). STUDY DESIGN: We performed a randomized, double-blinded, placebo-controlled trial in southern Brazil, from 2009 to 2011. Infants (<12 months of age) hospitalized with AB were recruited in 2 hospitals. Patients were randomized to receive either azithromycin or placebo, administered orally, for 7 days. At enrollment, clinical data were recorded and nasopharyngeal samples were collected for viral identification through immunofluorescence. Main outcomes were duration of oxygen requirement and length of hospitalization. RESULTS: One hundred eighty-four patients were included in the study (azithromycin 88 subjects, placebo 96 subjects). Baseline clinical characteristics and viral identification were not different between the groups studied. A virus was detected in 112 (63%) patients, and of those, 92% were positive for respiratory syncytial virus. The use of azithromycin did not reduce the median number of days of either hospitalization (P = .28) or oxygen requirement (P = .47). CONCLUSIONS: Azithromycin did not improve major clinical outcomes in a large sample of hospitalized infants with AB, even when restricting the findings to those with positive respiratory syncytial virus samples. Azithromycin therapy should not be given for AB because it provides no benefit and overuse increases overall antibiotic resistance.

Symptomatic parainfluenza virus infections in children undergoing hematopoietic stem cell transplantation.

Parainfluenza virus (PIV) infections cause significant mortality in adults undergoing hematopoietic stem cell transplantation (HSCT). Children are more prone to PIV infections than adults; however, data on the epidemiology of these infections in children undergoing HSCT are limited. This study examined the incidence of symptomatic PIV infections, risk factors for lower respiratory tract infection (LRTI), and the impact on mortality after pediatric HSCT. A total of 1028 children who underwent HSCT between 1995 and 2009 were studied. PIV infections were detected in 46 of the 738 patients tested for respiratory infection (6.2%). PIV infection was the most common symptomatic respiratory viral infection in this population. On multivariate logistic regression analysis, receipt of an allogeneic transplant (P < .0001) and total body irradiation-based conditioning (P < .0001) were associated with increased risk of acquiring symptomatic PIV infection. Of the 46 HSCT patients with PIV infection, 18 (39%) had an LRTI. LRTI was associated with PIV infection in the first 100 days post-HSCT (P = .006), use of steroids (P = .035), and absolute leukocyte count (ALC) <100 cells/µL at the onset of infection (P < .0001). An ALC of <500 cells/µL was associated with prolonged viral shedding (P = .045). Six (13%) HSCT patients died of PIV infection. Mortality was associated with African-American ethnicity (P = .013), LRTI (P = .002), use of steroids (P < .0001), mechanical ventilation (P < .0001), and ALC <100 cells/µL at the onset of infection (P = .01). PIV infection causes significant morbidity and mortality in children undergoing HSCT.

SARS-CoV-2 Complicated by Sinusitis and Co-Infection with Human Metapneumovirus.

A previously healthy 25-year-old Asian male was admitted with acute respiratory failure due to COVID-19 pneumonia to our intensive care unit. He received empiric therapy and higher level of respiratory support via a high flow nasal cannula. Notably, human metapneumovirus was detected from the nasopharyngeal swab by RT-PCR. Six days post-ICU admission, sinusitis was clinically and sonographically detected. SARS-CoV-2 was detected in the fluid aspirated from the antrum. The patient has made an uneventful recovery. Further studies are required to investigate co-infections with SARS-CoV-2 and other viruses.

Efficacy of four enrofloxacin treatment regimens against experimental infection in turkey poults with avian pneumovirus and Ornithobacterium rhinotracheale.

Drinking-water treatment with enrofloxacin is widely used to cure respiratory infections in turkeys. The current treatment regimen advises a 5-day treatment at 10 mg/kg body weight. Since enrofloxacin exerts a concentration-dependent activity it might be useful to provide the total treatment dose of 50 mg/kg total dose in a single-day treatment regimen. We therefore assessed whether single-day treatment regimens with 50 mg/kg body weight were clinically equivalent to the advised multiple-day treatment regimen with 10 mg/kg body weight for 5 days. For this purpose, five groups of 16 turkeys, 22 days old, were experimentally inoculated with avian metapneumovirus (APV) and Ornithobacterium rhinotracheale and subsequently treated in the drinking water with enrofloxacin, using either a single-day treatment regimen at 50 mg/kg body weight during a 5-h, 10-h or 20-h period or a standard 5-day treatment regimen at 10 mg/kg body weight/ day for 20 h. Although initially all dosage regimens cleared O. rhinotracheale from the trachea, 4 days after onset of treatment O. rhinotracheale bacteria were re-excreted in the single-day regimens but without worsening of the clinical symptoms. The 5-day treatment with 10 mg enrofloxacin/kg in turkeys provided the best results for the treatment of an O. rhinotracheale infection in turkeys by shortening the course and reducing the severity of clinical disease and by eliminating O. rhinotracheale from the respiratory tract without re-emergence. None of the used treatment regimens promoted the selection of bacterial clones with reduced susceptibility or resistance.

[Human metapneumovirus (HMPV) infections in young children]. / Zakazenia metapneumowirusem czlowieka (hMPV) u malych dzieci.

Human metapneumovirus (hMPV) is a recently discovered respiratory virus. hMPV, the second after respiratory syncytial virus (RSV), is leading cause of upper and lower respiratory tract infections mainly in infants and children. hMPV infections have been reported in many countries in all the world, in patients in every age and gender, but children under 5 years are most likely to be susceptible to infections caused by hMPV. The frequency of hMPV infections require hospitalization in this group is 5-10%. Late winter and early spring is the epidemic peak of hMPV infections in a lot of countries. The similar time of hMPV infections and another respiratory viruses is leading to appear coinfections. Many data reported higher frequency of double coinfections (RSV and hMPV), even 60-70%. This coinfections are responsible for 10-fold increase risk of admission children to a pediatric intensive care unit for mechanical ventilation. INF, AdV, PIV, EV are the other viruses cause coinfections with hMPV. The main laboratory method to diagnose hMPV infections is detect viral RNA and viral antigen in the sample.

Comparison of Clinical Characteristics of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Young Children.

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory tract infection in children, and clinical manifestations of these virus infections are considered similar. To investigate the differences in clinical characteristics between HMPV and RSV infections in young children, we prospectively enrolled children ＜ 3 years old who required hospitalization with acute respiratory tract infection due to HMPV or RSV at 10 hospitals in Japan. We enrolled 48 children with HMPV infection and 141 with RSV infection. Patients with HMPV infection were older than those with RSV infection. High-grade fever was more frequently observed in patients with HMPV infection, whereas no significant differences in respiratory symptoms were apparent. Abnormal serum lactate dehydrogenase values and consolidation shadows on chest X-ray were more frequently observed in patients with HMPV infection. During hospitalization, nasal mucus suction was more frequently required in patients with RSV infection. On the other hand, ß2-adrenergic agonists, corticosteroids, and leukotriene receptor antagonists were more frequently used in patients with HMPV infection. These findings suggest that HMPV and RSV infections show similar respiratory symptoms, but HMPV infection is more likely to lead to the development of pneumonia, at least among hospitalized young children.