Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study.

The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34-2.06-fold lower in males than females (P = 0.018 - < 0.001). IFN-ß, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.

Bluegill Picornavirus isolated from a mortality event involving Bluegill (Lepomis macrochirus) in the upper Mississippi River.

A mortality event involving an estimated 1,000 adult bluegills (Lepomis macrochirus) was observed in an ice-covered backwater lake of the upper Mississippi River near Alma, Wisconsin, in December of 2017. Macroscopic signs of disease included abdominal distension due to fluid accumulation within the internal organs as well as external and internal haemorrhaging. Histological evaluation revealed chronic peritonitis with peritoneal adhesions in all fish examined. Kidney, spleen and ascites fluid samples were collected from diseased bluegills and examined for the presence of pathogens. Bluegill picornavirus (BGPV) was isolated using tissue cell culture methods utilizing a recently developed, uncharacterized bluegill fry cell line (BF-4), and the presence of this virus was confirmed through molecular identification. The current geographic range, known susceptible hosts as well as historical epizootics associated with BPGV is discussed. The ability of BGPV to cause significant mortality in wild fish further emphasizes the importance of monitoring both wild and hatchery populations for this pathogen.

Paediatric intensive care admissions during the 2015-2016 Queensland human parechovirus outbreak.

AIM: The human parechovirus (HPeV) has emerged as a pathogen causing sepsis-like presentations in young infants, but there is a lack of data on HPeV presentations requiring intensive care support. We aimed to characterise the clinical presentation, disease severity, management and outcome of a population-based cohort of children with microbiologically confirmed HPeV infection requiring admission to paediatric intensive care units (PICUs) in Queensland, Australia during a recent outbreak. METHODS: This was a multicentre retrospective study of children admitted to PICU between 1 January 2015 and 31 December 2016 with confirmed HPeV infection. RESULTS: Thirty infants (median age 20 days) with HPeV genotype 3 were admitted to PICU, representing 16% of all children with HPeV admitted to hospital and 6.4% of non-elective PICU admissions in children <1 year of age. Children requiring PICU admission were younger than children admitted to hospital (P = 0.001). Apnoea, haemodynamic instability with tachycardia and seizures represented the main reasons for PICU admission. Eleven children (37%) required mechanical ventilation for a median duration of 62 h, 22 (73%) received fluid boluses and 7 (23%) were treated with vasoactive agents for a median duration of 53 h. Median length of stay was 2.62 days. A total of 24 children (80%) fulfilled sepsis criteria, 14 (47%) severe sepsis and 7 (23%) septic shock criteria. Eight (27%) had abnormal brain magnetic resonance imaging. No patient died. CONCLUSIONS: We confirm that HPeV infection is an important cause of sepsis-like syndrome in infants with substantial associated morbidity. Optimal management and long-term outcomes require further investigation.

Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

Pathogenicity of duck hepatitis A virus type 3 and innate immune responses of the ducklings to virulent DHAV-3.

Duck virus hepatitis caused by duck hepatitis A virus (DHAV) is an acute and contagious disease. To better understand the pathogenic mechanism of DHAV-3 in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DHAV-3 could infect many tissues, leading to pathological lesions, especially on the livers and spleen, and the host immune responses are activated in infection. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the livers and spleen, and antiviral innate immune response was established, but not sufficient to restrict the virus replication of lethal dose. Many major pattern recognition receptors (PRRs) (RIG-1, MDA5, and TLR7) are involved in the host immune response to DHAV-3, and the expression of interferon (IFNα, IFNß and IFNγ) and antiviral proteins (MX, OAS and PKR) are also up-regulated in the liver and spleen. The expression of most cytokines (IL-1ß, IL-2 and IL-6) was also up-regulated to different degrees and was various; the expression of IL-2 increased most significantly in liver. Our data provide a foundation for further study of the pathogenicity of duck virus hepatitis and extend our understanding of the immune responses of ducklings to DHAV-3 infection.

A novel passerivirus (family Picornaviridae) in an outbreak of enteritis with high mortality in estrildid finches (Uraeginthus sp.).

An enteric outbreak with high mortality (34/52, 65.4%) was recorded in 2014 in home-reared estrildid finches (Estrildidae) in Hungary. A novel passerivirus was identified in a diseased violet-eared waxbill using viral metagenomics and confirmed by RT-(q)PCR. The complete genome of finch picornavirus strain waxbill/DB01/HUN/2014 (MF977321) showed the highest amino acid sequence identity of 38.9%, 61.6%, 69.6% in P1cap, 2Chel and 3CproDpol, respectively, to passerivirus A1 (GU182406). A high viral load (6.58 × 1010 genomic copies/ml) was measured in a cloacal specimen and in the tissues (spinal cord, lung, and the intestines) of two additional affected finches. In addition to intestinal symptoms (diarrhoea), the presence of extra-intestinal virus suggests a generalized infection in this fatal disease, for which the passerivirus might be a causative agent.

Viruses associated with congenital tremor and high lethality in piglets.

The recently described atypical porcine pestivirus (APPV) has been associated with congenital tremor (CT) type A-II in piglets in different countries. Another important neurological pathogen of pigs is porcine teschovirus (PTV), which has been associated with non-suppurative encephalomyelitis in pigs with severe or mild neurological disorders. There have been no reports of APPV and/or PTV coinfection associated with CT or encephalomyelitis in Brazilian pig herds. The aim of this study was to describe the pathological and molecular findings associated with simultaneous infection of APPV and PTV in piglets with clinical manifestations of CT that were derived from a herd with high rates of CT-associated lethality. In 2017, three piglets from the same litter with CT died spontaneously. The principal pathological alterations in all piglets were secondary demyelination and hypomyelination at the cerebellum, brainstem and spinal cord confirmed by histopathology and luxol fast blue-cresyl violet stain. Additional significant pathological findings included multifocal neuronal necrosis, neuronophagia and gliosis found in the cerebral cortex and spinal cord of all piglets, while atrophic enteritis and mesocolonic oedema were observed in some of them. APPV and PTV RNA were detected in the central nervous system of affected piglets, and PTV was also detected in the intestine and faeces. The pathological alterations and molecular findings together suggest a dual infection due to APPV and PTV at this farm. Moreover, the combined effects of these pathogens can be attributed to the elevated piglet mortality, as coinfections involving PTV have a synergistic effect on the affected animals.

Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013.

We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R0) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y529 allele, which increases risk for rhinovirus C infection and asthma in human children. These results indicate that chimpanzees exhibit a species-wide genetic susceptibility to rhinovirus C and that this virus, heretofore considered a uniquely human pathogen, can cross primate species barriers and threatens wild apes. We advocate engineering interventions and prevention strategies for rhinovirus infections for both humans and wild apes.

A flavone-polysaccharide based prescription attenuates the mitochondrial dysfunction induced by duck hepatitis A virus type 1.

The principal target organ of duck hepatitis A virus type 1 (DHAV-1) is duckling liver, which is an energy-intensive organ and plays important roles in body's energy metabolism and conversion. As the "power house" of the hepatocytes, mitochondria provide more than 90% of the energy. However, mitochondria are much vulnerable to the oxidative stress for their rich in polyunsaturated fatty acids. Although previous researches have demonstrated that DHAV-1 could induce the oxidative stress in the serum of the infected ducklings, no related study on the mitochondria during the pathological process of DVH has been reported by far. To address this issue, we examined the HE stained tissue pathological slices, detected the hepatic SOD, CAT and GPX activities and MDA contents and analyzed the ATP content, mitochondrial ultrastructure and the mitochondrial SOD, GPX activities and MDA content in the liver tissues. The results showed that the hepatic redox status was significantly disturbed so that causing the mitochondrial dysfunction, ATP depletion and mitochondrial oxidative stress during the process of the DHAV-1 infection, and a prescription formulated with Hypericum japonicum flavone, Radix Rehmanniae Recens polysaccharide and Salvia plebeia flavone (HRS), which had been demonstrated with good anti-oxidative activity in serum, could effectively alleviate the hepatic injury and the oxidative stress in liver tissue induced by DHAV-1 thus alleviating the mitochondrial injury and oxidative stress. In a word, this research discovers the oxidative stress induced mitochondrial dysfunction and oxidative stress during the DVH pathological process and demonstrates HRS exerts good anti-oxidative activity in liver tissue to protect mitochondria against reactive oxygen species (ROS).

Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality.

Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. We evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. As comparative cohorts, 273 recipients with lower respiratory tract infection caused by respiratory syncytial virus (N=117), parainfluenza virus (N=120), or influenza (N=36) were analyzed. Factors associated with mortality were analyzed using Cox proportional hazard models. Among 569 subjects with rhinovirus upper respiratory tract infection and 128 subjects with rhinovirus lower respiratory tract infection, probabilities of overall mortality at 90 days were 6% and 41%, respectively (P<0.001). The survival rate after lower respiratory tract infection was not affected by the presence of co-pathogens (55% in patients with co-pathogens, 64% in patients without, P=0.34). Low monocyte count (P=0.027), oxygen use (P=0.015), and steroid dose greater than 1 mg/kg/day (P=0.003) before diagnosis were significantly associated with mortality among patients with lower respiratory tract infection in multivariable analysis. Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model. In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses. Our data suggest rhinovirus can contribute to severe pulmonary disease in immunocompromised hosts.

The Use of Polymerase Chain Reaction Amplification for the Detection of Viruses and Bacteria in Severe Community-Acquired Pneumonia.

BACKGROUND: Pathogens are often not identified in severe community-acquired pneumonia (CAP), and the few studies using polymerase chain reaction (PCR) techniques for virus detection are from temperate countries. OBJECTIVE: This study assesses if PCR amplification improves virus and bacteria detection, and if viral infection contributes to mortality in severe CAP in a tropical setting, where respiratory pathogens have less well-defined seasonality. METHODS: In this cohort study of patients with severe CAP in an intensive care unit, endotracheal aspirates for intubated patients and nasopharyngeal swabs for non-intubated patients were sent for PCR amplification for respiratory viruses. Blood, endotracheal aspirates for intubated patients, and sputum for non-intubated patients were analysed using a multiplex PCR system for bacteria. RESULTS: Out of 100 patients, using predominantly cultures, bacteria were identified in 42 patients; PCR amplification increased this number to 55 patients. PCR amplification identified viruses in 32 patients. In total, only bacteria, only viruses, and both bacteria and viruses were found in 37, 14, and 18 patients, respectively. The commonest viruses were influenza A H1N1/2009 and rhinovirus; the commonest bacterium was Streptococcus pneumoniae. Hospital mortality rates for patients with no pathogens, bacterial infection, viral infection, and bacterial-viral co-infection were 16.1, 24.3, 0, and 5.6%, respectively (p = 0.10). On multivariable analysis, virus detection was associated with lower mortality (adjusted odds ratio 0.12, 95% confidence interval 0.2-0.99; p = 0.049). CONCLUSIONS: Viruses and bacteria were detected in 7 of 10 patients with severe CAP with the aid of PCR amplification. Viral infection appears to be independently associated with lower mortality.

Neonatal Mortality, Vesicular Lesions and Lameness Associated with Senecavirus A in a U.S. Sow Farm.

A 300-sow farrow-to-finish swine operation in the United States experienced a sudden and severe increase in mortality in neonatal piglets with high morbidity followed by vesicular lesions on the snout and feet of adult females and males. Affected live piglets were submitted for diagnostic investigation. Samples tested polymerase chain reaction (PCR) negative for foot-and-mouth disease virus, porcine delta coronavirus, porcine epidemic diarrhoea virus, porcine rotavirus types A, B and C, transmissible gastroenteritis virus, and porcine reproductive and respiratory syndrome virus. Senecavirus A (SV-A) formerly known as Seneca Valley virus was detected by real-time reverse-transcription polymerase chain reaction (rRT-PCR) from serum, skin and faeces of piglets and from serum and faeces of sows. SV-A was isolated in cell culture from piglet samples. SV-A VP1 gene region sequencing from piglet tissues was also successful. A biosecurity and disease entry evaluation was conducted and identified potential biosecurity risks factors for the entry of new pathogens into the operation. This is the first case report in the United States associating SV-A with a clinical course of severe but transient neonatal morbidity and mortality followed by vesicular lesions in breeding stock animals. Veterinarians and animal caretakers must remain vigilant for vesicular foreign animal diseases and report suspicious clinical signs and lesions to state animal health authorities for diagnostic testing and further investigation.

Productive Infection of Human Embryonic Stem Cell-Derived NKX2.1+ Respiratory Progenitors with Human Rhinovirus.

UNLABELLED: Airway epithelial cells generated from pluripotent stem cells (PSCs) represent a resource for research into a variety of human respiratory conditions, including those resulting from infection with common human pathogens. Using an NKX2.1-GFP reporter human embryonic stem cell line, we developed a serum-free protocol for the generation of NKX2.1(+) endoderm that, when transplanted into immunodeficient mice, matured into respiratory cell types identified by expression of CC10, MUC5AC, and surfactant proteins. Gene profiling experiments indicated that day 10 NKX2.1(+) endoderm expressed markers indicative of early foregut but lacked genes associated with later stages of respiratory epithelial cell differentiation. Nevertheless, NKX2.1(+) endoderm supported the infection and replication of the common respiratory pathogen human rhinovirus HRV1b. Moreover, NKX2.1(+) endoderm upregulated expression of IL-6, IL-8, and IL-1B in response to infection, a characteristic of human airway epithelial cells. Our experiments provide proof of principle for the use of PSC-derived respiratory epithelial cells in the study of cell-virus interactions. SIGNIFICANCE: This report provides proof-of-principle experiments demonstrating, for the first time, that human respiratory progenitor cells derived from stem cells in the laboratory can be productively infected with human rhinovirus, the predominant cause of the common cold.

A multicenter outcomes analysis of children with severe rhino/enteroviral respiratory infection.

OBJECTIVES: To investigate the impact of human rhino/enteroviruses on morbidity and mortality outcomes in children with severe viral respiratory infection. DESIGN: Retrospective cohort study. SETTING: The ICU, either PICU or cardiac ICU, at three urban academic tertiary-care children's hospitals. PATIENTS: All patients with laboratory-confirmed human rhino/enteroviruses 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 519 patients included in our analysis. The median patient age was 2.7 years. The median hospital and ICU lengths of stay were 4 days and 2 days, respectively. Thirty-four percent of patients had a history of asthma, and 25% of patients had a chronic medical condition other than asthma. Thirty-two percent of patients required mechanical ventilation. Eleven patients (2.1%) did not survive to hospital discharge. The rate of viral coinfection was 12.5% and was not associated with mortality. Predisposing factors associated with increased mortality included immunocompromised state (p < 0.001), ICU admission severity of illness score (p < 0.001), and bacterial coinfection (p = 0.003). CONCLUSIONS: There is substantial morbidity associated with severe respiratory infection due to human rhino/enteroviruses in children. Mortality was less severe than reported in other respiratory viruses such as influenza and respiratory syncytial virus. The burden of illness from human rhino/enteroviruses in the ICU in terms of resource utilization may be considerable.

[Etiology of fatal pneumonia caused by influenza A(H1N1)pdm2009 virus during the pandemic in Russia].

The results of the study of the autopsy materials from 61 patients with the diagnosis of pneumonia received by virological and genetic methods are reviewed. The materials were studied at the Influenza Etiology and Epidemiology Center of the Ivanovsky Institute of Virology, Ministry of Health and Social Development of the Russian Federation, during epidemic seasons 2009-2010 and 2010-2011. The data were analyzed with respect to age, sex, comorbidity diseases and identified on the groups of the risk of severe forms of the disease. The presence of the pandemic influenza virus strain RNA was confirmed in 70.5% of materials; RNA of influenza B was detected in 1.2% cases. The co-infections caused by the bocavirus, adenovirus, parainfluenza virus type 2 and 4, rhinovirus, and streptococcus were detected only in 19.7%. In most cases, the influenza virus was the etiologic agent of lethal pneumonia, which justifies the necessity of the early etiological diagnosis and treatment with antiviral drugs.

Human rhinovirus infections of the lower respiratory tract in hematopoietic stem cell transplant recipients.

BACKGROUND: Human rhinoviruses (HRVs) are a common cause of upper respiratory infection (URI) in hematopoietic stem cell transplant (HSCT) recipients; yet, their role in lower respiratory illness is not well understood. METHODS: We performed a retrospective chart review of HSCT recipients with HRV infection from the time molecular detection methods were implemented at our institution in 2008. Factors associated with proven or possible HRV pneumonia at the first HRV detection were evaluated by univariate and multivariate analysis. We then characterized all episodes of proven and possible HRV pneumonia from the initial HRV infection through a 1-year follow-up period. RESULTS: Between 2008 and 2011, 63 HSCT recipients had ≥1 documented HRV infections. At first HRV detection, 36 (57%) patients had HRV URI and 27 (43%) had proven or possible HRV pneumonia; in multivariate analysis, hypoalbuminemia (odds ratio [OR] 9.5, 95% confidence interval [CI] 1.3-71.7; P = 0.03) and isolation of respiratory co-pathogen(s) (OR 24.2, 95% CI 2.0-288.4; P = 0.01) were independently associated with pneumonia. During the study period, 22 patients had 25 episodes of proven HRV pneumonia. Fever (60%), cough (92%), sputum production (61%), and dyspnea (60%) were common symptoms. Fifteen (60%) episodes demonstrated bacterial (n = 7), fungal (n = 5), or viral (n = 3) co-infection. Among the remaining 10 (40%) cases of HRV monoinfection, patients' oxygen saturations ranged from 80% to 97% on ambient air, and computed tomography scans showed peribronchiolar, patchy, ground glass infiltrates. CONCLUSIONS: HRV pneumonia is relatively common after HSCT and frequently accompanied by bacterial co-infection. As use of molecular assays for respiratory viral diagnosis becomes widespread, HRV will be increasingly recognized as a significant cause of pneumonia in immunocompromised hosts.

Rhinovirus and other respiratory viruses exert different effects on lung allograft function that are not mediated through acute rejection.

BACKGROUND: Community acquired respiratory virus (CARV) infections in lung transplant recipients (LTR) have been associated with adverse outcomes, including acute rejection (AR) and decline in allograft function, in some but not in all studies. METHODS: Spirometry and transbronchial biopsy results of LTR diagnosed with CARV infection over a two-yr period were extracted from clinical records. Primary outcomes, studied at 1-2.5 months postinfection, were as follows: (i) incidence of biopsy-proven AR (grade >A0) and (ii) allograft function, defined by forced expiratory volume in one s (FEV(1)). A reference group of biopsies (n = 526) collected during the study period established the baseline incidence of AR. Rhinovirus (RV) and non-rhinovirus (non-RV) infections were analyzed as subgroups. RESULTS: Eighty-seven cases of CARV infection were identified in 59 subjects. Incidences of AR were similar in the post-CARV and reference groups and did not differ significantly after RV vs. non-RV infection. Allograft function declined significantly after non-RV infection, but not after RV infection. CONCLUSIONS: In LTR, CARV infections other than RV are associated with allograft dysfunction at 1-2.5 months after infection. However, CARVs do not appear associated with AR at this time point. The impact of specific CARVs on lung allografts, including the development of chronic allograft rejection, merits further study.

Fatal respiratory infections associated with rhinovirus outbreak, Vietnam.

During an outbreak of severe acute respiratory infections in 2 orphanages, Vietnam, 7/12 hospitalized children died. All hospitalized children and 26/43 children from outbreak orphanages tested positive for rhinovirus versus 9/40 control children (p = 0.0005). Outbreak rhinoviruses formed a distinct genetic cluster. Human rhinovirus is an underappreciated cause of severe pneumonia in vulnerable groups.