Sudden Infant Death Associated with Rhinovirus Infection.

A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant's environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.

Rhinovirus-induced wheeze was associated with asthma development in predisposed children.

AIM: This study explored whether early-life factors, such as rhinovirus-induced wheeze and allergic sensitisation, were related to asthma at 11 years of age. METHODS: We focused on 107 children aged 6-48 months, who attended the paediatric emergency department at Astrid Lindgren's Children's Hospital in Stockholm, Sweden, with acute wheeze in 2008-2012. They also attended follow-up visits at 11 years of age and were compared with 46 age-matched healthy controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with logistic regression. RESULTS: We found that 62.6% of the acute wheeze cases had asthma at 11 years of age. Rhinoviruses at inclusion were the only common airway viruses associated with an increased asthma risk (OR 2.4, 95% CI 1.02-5.6). Other increased risks were parental heredity for asthma and/or allergies (adjusted OR 3.4, 95% CI 1.1-9.9) and allergic sensitisation at 2 years of age (adjusted OR 3.0, 95% CI 1.02-8.7). The highest prevalence of asthma was when children had both rhinovirus-induced wheeze at inclusion and allergic sensitisation at 7 years of age. CONCLUSION: Our findings highlight the importance of hereditary factors and allergic sensitisation on the development of asthma and suggest that rhinoviruses are associated with asthma development in predisposed children.

A Case Series of Infants 60 Days of Age or Younger With Human Parechovirus (PeV) Meningitis From a New York City Pediatric Emergency Department.

Human parechovirus is a relatively lesser known virus that has recently spread across the United States, primarily affecting newborns and young infants. A particular strain of parechovirus, PeV-A3, has been found in the cerebrospinal fluid studies of many young patients in the spring and summer of 2022; however, short- and long-term neurologic effects of this virus are often not well known. We present a case series of 4 infants, 60 days of age or younger, found to have human parechovirus meningitis. Our retrospective study found that none of the 4 infants presented with any significant neurological findings, nor did they develop any specific neurologic signs or symptoms during their hospitalizations. Patients should continue to be monitored for long-term neurological and neurodevelopmental sequelae.

Asthma Exacerbations: Patient Features and Potential Long-Term Implications.

Asthma exacerbations occur in the context of a complex interplay between external exposures and host factors. Respiratory tract viral infections, in particular rhinovirus, are dominant initiators of exacerbations, with allergens and other inhalation exposures as additional key contributors. The presence of underlying type II inflammation, with associated biomarker elevations, is a major driver of exacerbation risk and mechanism, as evidenced by the consistent reduction of exacerbations seen with biologics targeting these pathways. Several genetic polymorphisms are associated with exacerbations, and while they may individually have small effects, they are cumulatively important and magnified by environmental exposures. A history of exacerbations predicts future exacerbations with potentially negative implications on long-term lung health.

Histamine-releasing factor in severe asthma and rhinovirus-associated asthma exacerbation.

BACKGROUND: Histamine-releasing factor (HRF) is implicated in allergic diseases. We previously showed its pathogenic role in murine models of asthma. OBJECTIVE: We aim to present data analysis from 3 separate human samples (sera samples from asthmatic patients, nasal washings from rhinovirus [RV]-infected individuals, and sera samples from patients with RV-induced asthma exacerbation) and 1 mouse sample to investigate correlates of HRF function in asthma and virus-induced asthma exacerbations. METHODS: Total IgE and HRF-reactive IgE/IgG as well as HRF in sera from patients with mild/moderate asthma or severe asthma (SA) and healthy controls (HCs) were quantified by ELISA. HRF secretion in culture media from RV-infected adenovirus-12 SV40 hybrid virus transformed human bronchial epithelial cells and in nasal washings from experimentally RV-infected subjects was analyzed by Western blotting. HRF-reactive IgE/IgG levels in longitudinal serum samples from patients with asthma exacerbations were also quantified. RESULTS: HRF-reactive IgE and total IgE levels were higher in patients with SA than in HCs, whereas HRF-reactive IgG (and IgG1) level was lower in asthmatic patients versus HCs. In comparison with HRF-reactive IgElow asthmatic patients, HRF-reactive IgEhigh asthmatic patients had a tendency to release more tryptase and prostaglandin D2 on anti-IgE stimulation of bronchoalveolar lavage cells. RV infection induced HRF secretion from adenovirus-12 SV40 hybrid virus transformed bronchial epithelial cells, and intranasal RV infection of human subjects induced increased HRF secretion in nasal washes. Asthmatic patients had higher levels of HRF-reactive IgE at the time of asthma exacerbations associated with RV infection, compared with those after the resolution. This phenomenon was not seen in asthma exacerbations without viral infections. CONCLUSIONS: HRF-reactive IgE is higher in patients with SA. RV infection induces HRF secretion from respiratory epithelial cells both in vitro and in vivo. These results suggest the role of HRF in asthma severity and RV-induced asthma exacerbation.

EEG and clinical characteristics of neonatal parechovirus encephalitis.

RATIONALE: Human parechoviruses (HPeVs) are single -stranded ribonucleic (RNA) viruses belonging to the picornaviridae family with characteristics similar to enteroviruses. They either cause mild respiratory and gastrointestinal or no symptoms in older children and adults but can be a major cause of central nervous system (CNS) infection in the neonatal period and demonstrate a seasonal predilection. Starting in March 2022, we saw eight patients with polymerase chain reaction (PCR) proven HPeV encephalitis with seizures and some electroencephalographic (EEG) features raising concerns for neonatal genetic epilepsy. Although cerebrospinal fluid (CSF) and imaging findings have been previously described, there is little emphasis on seizure presentation and EEG findings of HPeV in the literature. We wish to highlight the EEG and seizure semiology of HPeV encephalitis that may mimic a genetic neonatal epilepsy syndrome. METHODS: Retrospective chart review of all neonates seen at Children's Health Dallas, UTSW Medical Center between 03/18/2022-06/01/2022 with HPeV encephalitis. RESULTS: Term neonates (postmenstrual age 37-40 weeks) presented with a variable combination of fever, lethargy, irritability, poor oral intake, erythematous rash, and focal seizures. One patient with a single episode of limpness and pallor did not undergo EEG due to a low suspicion for seizures. CSF indices were normal in all patients. EEG was abnormal in all patients where performed (n = 7). EEG features included dysmaturity (7/7, 100 %); excessive discontinuity (6/7, 86 %); excessive asynchrony (6/7, 86 %); multifocal sharp transients (7/7, 100 %). Focal/multifocal seizures were captured in 6/7 (86 %); tonic in 3/7 (42 %) and described as migrating in 2 patients. Subclinical seizures were noted in 6/7 (86 %) with status epilepticus in 5/7 (71 %) patients. In 2/7 (28 %) the EEG showed a burst suppression pattern with poor state variation and voltages of < 5-10 uV/mm during the inter-burst intervals. Repeat EEG (3-11 days post initial EEG) showed improvement in 3 of 4 patients. No patient had ongoing seizures beyond day two of admission (22.5 h after EEG initiation). MRI showed extensive restricted diffusion in the supratentorial white matter, thalami, and less frequently the cortex, mimicking imaging findings of a metabolic or hypoxic-ischemic encephalopathy (7/8). Seizures responded within 36 h of presentation to treatment with acute bolus doses of medications. One patient died due to diffuse cerebral edema and status epilepticus. Six patients had a normal clinical exam at discharge. All patients started on maintenance antiseizure medication (ASM) were sent home on either a single medication or two medications (phenobarbital and levetiracetam) with plans to wean phenobarbital after discharge. CONCLUSIONS: HPeV is a rare cause of seizures and encephalopathy in neonates. Prior studies have emphasized specific patterns of white matter injury on imaging. We demonstrate that HPeV also commonly presents with clonic or tonic seizures with or without apnea and often subclinical multifocal and migrating focal seizures that could mimic a genetic neonatal epilepsy syndrome. Interictal EEG shows a dysmature background with excessive asynchrony, discontinuity, burst-suppression pattern, and multifocal sharp transients. However, we note that 100 % of patients responded quickly to standard ASM, and did not have seizures after hospital discharge- a factor that can help distinguish it from a genetic epilepsy syndrome.

Persistent Rhinovirus Infection in a Child With Leukemia.

Human Rhinovirus (HRV) is one of the most common pathogens causing acute respiratory tract infections in infants and children. Several reports suggest that HRV has the potential to cause chronic infection after an acute viral infection in an immunosuppressed patient. Although chronic HRV infection has been reported in lung transplant recipients, patients with hypogammaglobulinemia and cystic fibrosis, the duration and severity of HRV infection remain unclear. In this study, we present a case of persistent HRV infection in a stem cell transplanted leukemia patient. This report raises several questions regarding the risk factors, duration, and severity of persistent HRV infection in acute leukemia patients, which warrants prospective and longitudinal studies.

Colecistite alitiasíca em paciente com Hepatite A: relato de caso / Alithiasic cholecystitis in a patient with Hepatitis A: case report

A hepatite A é doença que, apesar de significativa redução na incidência nacional nos últimos 10 anos, se apresenta com o dobro da incidência nacional na cidade de São Paulo. Vírus da família Picornaviridae, que foi isolado apenas recentemente, em 1973, representa relevância na saúde pública no cenário de países em desenvolvimento e subdesenvolvidos, com maior prevalência em países da América Latina, África e Sul do continente asiático. Segundo Boletim Epidemiológico de Hepatites Virais de 2022 do Ministério da Saúde, entre 2000 e 2021 foram notificados ao SINAN 168.175 casos de Hepatite A, o que corresponde a 23,4% de todas as notificações de hepatites virais realizadas no período. Atualmente aliada a melhoria do acesso a água limpa, educação em saúde para população e saneamento básico, há a vacina para Hepatite A incluída no Programa Nacional de Imunização desde 2014, com extensão de cobertura a partir de 2017. A infecção pelo HAV em crianças é geralmente oligossintomática ou até mesmo assintomática, enquanto nos adultos geralmente se apresenta com sintomas possivelmente graves. Na medida em que há melhora nas condições socioeconômicas a prevalência das infecções se concentra entre adultos, assim apresentando um paradoxo da redução da incidência com aumento de morbidade associado. A hepatite A é doença que possui no ser humano seu único reservatório conhecido e, entre as hepatites virais, é a que apresenta maior relação com hepatite colestática. A colecistite alitiásica se apresenta em menos de 5-10% dos quadros diagnosticados de colecistite, com incidência desconhecida dentre as complicações colestáticas associadas a infecção por HAV. O presente trabalho tem como objetivo relatar o caso de uma paciente de 34 anos que foi atendida pela equipe de Gastroenterologia no Hospital do Servidor Público Municipal no ano de 2022 com colecistite atrelada a infecção pelo vírus da hepatite A, porém sem caracterização de colelitíase associado: um quadro de colecistite alitiásica. Palavras-chave: Hepatite Viral A. Colecistite Acalculosa. Colestase Extra-hepática.

COVID-19, rinovirus y asma... ¿Una mala combinación? / COVID-19, rhinovirus and asthma... a bad conmbination?

La pandemia de COVID-19 enfrentó a la humanidad a un gran desafío y hemos ido aprendiendo a medida que avanzó. La aparición de este virus, su comportamiento por si solo y en conjunto con los otros virus nos mantuvo alerta.. Los pacientes pediátricos asmáticos, a pesar de lo que se pensó en un principio, son menos afectados y hacen un cuadro clínico más leve. Objetivo: presentar un caso clínico de un paciente asmático, con una evolución tortuosa por co-infección SARS-CoV-2 y Rinovirus (RV) y revisión de la litaratura. Se trata de un escolar de 6 años, asmático con mal control, con 2 dosis de vacuna anti SARS-CoV-2, que presento un estado asmático por rinovirus y posterior evolución con neumonía grave por SARS-CoV-2, requiriendo ventilación mecánica invasiva y estadía en UCI Pediátrica. Es probable que la gravedad del caso presentado se deba al mal control del asma antes de la infección, ya que se ha visto que los niños asmáticos alérgicos presentan un factor protector para infección grave por SARS-CoV-2, lo cual esta supeditado a un buen control de su enfermedad basal.

The COVID-19 pandemic presented a great challenge and we have been learning as it has progressed. The appearance of this virus, its behavior by itself and in conjunction with the other viruses kept us alert. Pediatric asthmatic patients, despite what was initially thought, are less affected and present a milder clinical picture. Objective: to present a clinical case of an asthmatic patient, with a tortuous evolution due to SARS-CoV-2 and Rhinovirus (RV) co-infection and a literature review. This is a 6-year-old schoolboy, asthmatic with poor control, with 2 doses of the SARS-CoV-2 vaccine, who presents asthmatic status due to rhinovirus and subsequent evolution with severe pneumonia due to SARS-CoV-2, requiring invasive mechanical ventilation and stay in Pediatric ICU. It is likely that the severity of the case presented is due to poor asthma control before infection, since it has been seen that allergic asthmatic children present a protective factor for severe infection by SARS-CoV-2, which is subject to good control of his basal disease.

Rhinovirus Infection and Virus-Induced Asthma.

While the aetiology of asthma is unclear, the onset and/or exacerbation of asthma may be associated with respiratory infections. Virus-induced asthma is also known as virus-associated/triggered asthma, and the reported main causative agent is rhinovirus (RV). Understanding the relationship between viral infections and asthma may overcome the gaps in deferential immunity between viral infections and allergies. Moreover, understanding the complicated cytokine networks involved in RV infection may be necessary. Therefore, the complexity of RV-induced asthma is not only owing to the response of airway and immune cells against viral infection, but also to allergic immune responses caused by the wide variety of cytokines produced by these cells. To better understand RV-induced asthma, it is necessary to elucidate the nature RV infections and the corresponding host defence mechanisms. In this review, we attempt to organise the complexity of RV-induced asthma to make it easily understandable for readers.

Effects of COVID-19 and Social Distancing on Rhinovirus Infections and Asthma Exacerbations.

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the "common cold" and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae.

Parechovirus A infection and risk of gastroenteritis in children: A systematic review and meta-analysis.

Parechovirus A (PeV-A) belongs to the genus Parechovirus in the family Picornaviridae associated with gastroenteritis illness, particularly in children, but prior studies have produced ambiguous results. This study aimed to provide a systematic review of the PeV-A prevalence in paediatric patients with gastroenteritis and the association between PeV-A infection and the risk of gastroenteritis. A systematic search of the literature was conducted in Embase, PubMed, Scopus, and Web of Science, in combination with the reference lists of potentially relevant articles. A random effect-based model was applied to analyse data from included studies. The pooled odds ratio (OR) and 95% confidence interval (CI) were used for assessing the risk between PeV-A and gastroenteritis. A total of 41 studies assessing 21,850 cases and 1746 healthy controls were analysed. The overall prevalence of PeV-A among paediatric patients with gastroenteritis was 10.4% (95% CI: 7.9%-13.2%), while it was estimated at 8.1% (95% CI: 5.1%-11.7%) based on studies only investigating children without gastroenteritis. The pooled OR for all eight case-control studies was 1.079 (95% CI: 0.730-1.597), indicating there was no statistically significant association. PeV-A genotype 1 was the most frequent genotype of PeV-A infection in children with gastroenteritis. The PeV-A prevalence in cases of gastroenteritis is higher than that in children without gastroenteritis. However, the present meta-analysis did not indicate a statistically significant association between PeV-A infection and risk of gastroenteritis. Given the considerable heterogeneity and various sample sizes among the included studies, relevant investigations in the future should be carried out based on a large-scale population.

Cluster analysis of nasal cytokines during rhinovirus infection identifies different immunophenotypes in both children and adults with allergic asthma.

BACKGROUND: Infection with rhinovirus (RV) is a major risk factor for disease exacerbations in patients with allergic asthma. This study analysed a broad set of cytokines in the noses of children and adults with asthma during RV infection in order to identify immunophenotypes that may link to virus-induced episodes. METHODS: Nasal wash specimens were analysed in children (n = 279 [healthy, n = 125; stable asthma, n = 64; wheeze, n = 90], ages 2-12) who presented to a hospital emergency department, and in adults (n = 44 [healthy, n = 13; asthma, n = 31], ages 18-38) who were experimentally infected with RV, including a subset who received anti-IgE. Cytokines were measured by multiplex bead assay and data analysed by univariate and multivariate methods to test relationships to viral load, allergic status, airway inflammation, and clinical outcomes. RESULTS: Analysis of a core set of 7 cytokines (IL-6, CXCL8/IL-8, IL-15, EGF, G-CSF, CXCL10/IP-10 and CCL22/MDC) revealed higher levels in children with acute wheeze versus those with stable asthma or controls. Multivariate analysis identified two clusters that were enriched for acutely wheezing children; one displaying high viral load ("RV-high") with robust secretion of CXCL10, and the other displaying high IgE with elevated EGF, CXCL8 and both eosinophil- and neutrophil-derived mediators. Broader assessment of 39 cytokines confirmed that children with acute wheeze were not deficient in type 1 anti-viral responses. Analysis of 18 nasal cytokines in adults with asthma who received RV challenge identified two clusters; one that was "RV-high" and linked to robust induction of anti-viral cytokines and anti-IgE; and the other associated with more severe symptoms and a higher inflammatory state featuring eosinophil and neutrophil factors. CONCLUSIONS: The results confirm the presence of different immunophenotypes linked to parameters of airway disease in both children and adults with asthma who are infected with RV. Such discrepancies may reflect the ability to regulate anti-viral responses.

A severe case of human rhinovirus A45 with central nervous system involvement and viral sepsis.

BACKGROUND: Rhinovirus is a common viral aetiology of upper respiratory infection and is mostly associated with common cold or flu-like illness. Although rhinovirus has been recognized as a pathogen for lower respiratory infections in severe cases credited to advances in molecular detection, central nervous system involvement and multiorgan dysfunction are extremely rare. CASE PRESENTATION: A previously healthy 10-year-old girl developed fever, sore throat and conjunctive injection after contact with an upper respiratory infection patient, followed by seizures, haematuria, and severe diarrhoea. She experienced viral sepsis and multiorgan dysfunction after admission. Cerebral computed tomography showed significant diffuse encephaledema. Cerebrospinal fluid analysis showed significantly elevated protein levels. After her consciousness disturbance improved, she still took a long time to recover from haematuria and diarrhoea. We identified a rarely reported rhinovirus A45 in her oropharyngeal and anal swabs by metagenomic next-generation sequencing, and bacterial culture of blood specimens yielded negative results. CONCLUSIONS: This case presents a patient with severe rhinovirus infection, which was very likely responsible for her central nervous system symptoms and viral sepsis.

Neuroimaging Findings in Parechovirus Encephalitis: A Case Series of Pediatric Patients.

BACKGROUND: Human parechovirus infection can cause parechovirus encephalitis in neonates and should be considered as a differential diagnosis in the emergency department. Neuroimaging features of parechovirus encephalitis have been described in neonates and young infants, but there is a paucity of literature regarding magnetic resonance imaging brain injury patterns in older children. We aim to present three cases of parechovirus encephalitis, showing distinctive magnetic resonance imaging brain patterns of injury in two newborns and, for the first time, in an adolescent. METHODS: We conducted a retrospective review of parechovirus encephalitis cases in our pediatric hospital. Clinical information and neuroimaging findings are described in detail. RESULTS: Classical neuroimaging findings in neonatal parechovirus encephalitis include restricted diffusion of the subcortical and periventricular white matter with frontoparietal predominance, in association with corpus callosum signal abnormality and bilateral swollen thalami. Parechovirus encephalitis in the adolescent appeared with an additional pattern of white matter signal abnormality in the corona radiata in continuity with the corticospinal tracts. CONCLUSIONS: Parechovirus encephalitis should be considered in the differential diagnosis when magnetic resonance imagingdemonstrates white matter injury with typical (sunburst type) distribution in the deep and periventricular white matter in both neonates and adolescents, especially in those with comorbidities or therapy that lead to an immunosuppressive status.

Rhinovirus-Induced Cytokine Alterations With Potential Implications in Asthma Exacerbations: A Systematic Review and Meta-Analysis.

BACKGROUND: Rhinovirus (RV) infections are a major cause of asthma exacerbations. Unlike other respiratory viruses, RV causes minimal cytotoxic effects on airway epithelial cells and cytokines play a critical role in its pathogenesis. However, previous findings on RV-induced cytokine responses were largely inconsistent. Thus, this study sought to identify the cytokine/chemokine profiles induced by RV infection and their correlations with airway inflammatory responses and/or respiratory symptoms using systematic review, and to determine whether a quantitative difference exists in cytokine levels between asthmatic and healthy individuals via meta-analysis. METHODS: Relevant articles were obtained from PubMed, Scopus, and ScienceDirect databases. Studies that compared RV-induced cytokine responses between asthmatic and healthy individuals were included in the systematic review, and their findings were categorized based on the study designs, which were ex vivo primary bronchial epithelial cells (PBECs), ex vivo peripheral blood mononuclear cells (PBMCs), and human experimental studies. Data on cytokine levels were also extracted and analyzed using Review Manager 5.4. RESULTS: Thirty-four articles were included in the systematic review, with 18 of these further subjected to meta-analysis. Several studies reported the correlations between the levels of cytokines, such as IL-8, IL-4, IL-5, and IL-13, and respiratory symptoms. Evidence suggests that IL-25 and IL-33 may be the cytokines that promote type 2 inflammation in asthmatics after RV infection. Besides that, a meta-analysis revealed that PBECs from children with atopic asthma produced significantly lower levels of IFN-ß [Effect size (ES): -0.84, p = 0.030] and IFN-λ (ES: -1.00, p = 0.002), and PBECs from adult atopic asthmatics produced significantly lower levels of IFN-ß (ES: -0.68, p = 0.009), compared to healthy subjects after RV infection. A trend towards a deficient production of IFN-γ (ES: -0.56, p = 0.060) in PBMCs from adult atopic asthmatics was observed. In lower airways, asthmatics also had significantly lower baseline IL-15 (ES: -0.69, p = 0.020) levels. CONCLUSION: Overall, RV-induced asthma exacerbations are potentially caused by an imbalance between Th1 and Th2 cytokines, which may be contributed by defective innate immune responses at cellular levels. Exogenous IFNs delivery may be beneficial as a prophylactic approach for RV-induced asthma exacerbations. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=184119, identifier CRD42020184119.