Hospitalized Children With Common Human Coronavirus Clinical Impact of Codetected Respiratory Syncytial Virus and Rhinovirus.

BACKGROUND: The clinical impact of common human coronavirus (cHCoV) remains unclear. We studied the clinical manifestations of pediatric cHCoV infections and the possible modifying effects of codetected human rhinovirus (RV) and respiratory syncytial virus (RSV). METHODS: We used data from an 11-year-long prospective study of hospitalized children with community-acquired respiratory tract infections. Nasopharyngeal aspirates were analyzed with real-time polymerase chain reaction assay for cHCoV OC43, NL63, HKU1 and 229E, and 15 other respiratory viruses. We assessed disease severity based on the clinical factors hospitalization length, oxygen requirement, other respiratory support and supplementary fluids. RESULTS: cHCoV was detected in 341 (8%) of 4312 children. Among 104 children with single cHCoV detections, 58 (56%) had lower respiratory tract infection (LRTI) and 20 (19%) developed severe disease. The proportion with severe disease was lower among single cHCoV detections compared with single RSV detections (338 of 870; 39%), but similar to single RV detections (136 of 987; 14%). Compared with single cHCoV, codetected cHCoV-RSV was more often associated with LRTI (86 of 89; 97%) and severe disease (adjusted odds ratio, 3.3; 95% confidence interval: 1.6-6.7). LRTI was more frequent in codetected cHCoV-RV (52 of 68; 76%) than single cHCoV, but the risk of severe disease was lower (adjusted odds ratios, 0.3; 95% confidence interval: 0.1-1.0). CONCLUSIONS: cHCoV was associated with severe LRTI in hospitalized children. Viral codetections were present in two-thirds. Codetections of cHCoV-RV were associated with lower proportions of severe disease, suggesting a modifying effect of RV on HCoV.

Status asthmaticus requiring extracorporeal membrane oxygenation associated with rhinovirus infection.

Objective: Evolving research links human rhinovirus (HRV) with status asthmaticus (SA) as well as severe respiratory illness in patients with atopy and asthma. This case series reviews five episodes of HRV-associated SA that required extracorporeal membrane oxygenation (ECMO). Methods: Charts of four patients, five total episodes of ECMO, with SA secondary to HRV were reviewed in this IRB-approved case series. Outcomes included demographic information, past medical history, clinical parameters and spirometry. Results: Patients (three male, one female), mean age 9 years (range 7-12 years) at the time of admission, were African American, on Medicaid, carried a diagnosis of persistent asthma, and had documented non-adherence to prescribed, daily controller medications. One patient had passive smoke exposure. All patients had a mean IgE of 734 (range 12-2497) with seasonal allergic rhinitis was diagnosed in three patients. Cases occurred in spring (3/5) and fall (2/5). Venous/venous ECMO (4/5) or venous/arterial ECMO (1/5) was continued for a mean duration of 4.2 days (range 3-7 days). Spirometry after hospitalization had a mean FEV1 of 1.59 L (81% predicted, range 69%-91%), and an FEF25%-75% 1.13 L (47.5% predicted, range 41%-65%) at an average of 16.7 weeks post ECMO. Conclusions: This case series highlights the association between persistent, poorly controlled asthma and severe SA with HRV infection resulting in ECMO. Despite life-threatening illness, these patients did not demonstrate significant large-airway obstruction following infection. However, patients showed persistently abnormal small airway function, which could be a risk factor or early evidence of vulnerability to infection.

Parechovirus A Pathogenesis and the Enigma of Genotype A-3.

ParechovirusA is a species in the Parechovirus genus within the Picornaviridae family that can cause severe disease in children. Relatively little is known on ParechovirusA epidemiology and pathogenesis. This review aims to explore the ParechovirusA literature and highlight the differences between ParechovirusA genotypes from a pathogenesis standpoint. In particular, the curious case of Parechovirus-A3 and the genotype-specific disease association will be discussed. Finally, a brief outlook on ParechovirusA research is provided.

Are rhinoviruses implicated in the pathogenesis of sinusitis and chronic rhinosinusitis exacerbations? A comprehensive review.

BACKGROUND: Rhinovirus (RV) infections are the most common cause of viral upper respiratory infections (URIs), and in the majority of persons they are self-limiting. However, in others, viral URIs can progress to bacterial sinusitis and induce chronic rhinosinusitis (CRS) exacerbations. METHODS: We conducted a comprehensive Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) review through April 2018 based on MEDLINE, EMBASE, Web of Science-Science Citation Index (SCI), and Conference Proceedings Citation Index- Science (CPCI-S) using keywords: RV, respiratory virus, sinusitis, and airway epithelial cells. The goal of this systematic review was to: (1) determine the prevalence between RV and CRS, (2) study the changes that occur after experimental RV inoculation, (3) investigate the pathophysiologic mechanisms by which RV induces sinonasal inflammation, and (4) explore the treatment options available for RV-associated sinusitis. Data regarding study design, research question, intervention, subjects, outcomes, and biases was extracted. RESULTS: The initial search yielded 2395 unique abstracts, of which 614 were selected for full-text review; 147 were included in the final review. We determined that (1) the prevalence of RV infections is increased in those with CRS, (2) humans challenged in vivo with RV secrete local inflammatory mediators with radiographic mucosal thickening, (3) RV species RV-A and RV-C challenges in vitro to sinonasal epithelia produce robust cytokine responses and differential gene changes, and (4) no current therapies have produced consistent and significant resolution of disease. CONCLUSION: RV infections are common in persons with CRS, and incite inflammatory reactions that may result in CRS exacerbations and progression of disease. Further studies assessing RV species, and the host-virome response are required to develop new strategies targeting RV-induced CRS.

Impact of Rhinovirus Infections in Children.

Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection's epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.

Distinct transcriptional modules in the peripheral blood mononuclear cells response to human respiratory syncytial virus or to human rhinovirus in hospitalized infants with bronchiolitis.

Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection-comparatively to HRV infection-was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.

Respiratory Tract Infections and Voice Quality in 4-Year-old Children in the STEPS Study.

OBJECTIVES: Health-related factors are part of the multifactorial background of dysphonia in children. Respiratory tract infections affect the same systems and structures that are used for voice production. The purpose of this study was to investigate if the number of respiratory tract infections or the viral etiology were significant predictors for a more hoarse voice quality. METHODS: The participants were 4-year-old children who participated in the multidisciplinary STEPS study (Steps to the Healthy Development and Well-being of Children) where they were followed up from pregnancy or birth to 4 years of age. Data were collected through questionnaires and a health diary filled in by the parents. Some of the children were followed up more intensively for respiratory tract infections during the first 2 years of life, and nasal swab samples were taken at the onset of respiratory symptoms. Our participants were 489 of these children who had participated in the follow-up for at least 1 year and for whom data on respiratory tract infections and data on voice quality were available. RESULTS: The number of hospitalizations due to respiratory tract infections was a significant predictor for a more hoarse voice quality. Neither the number of rhinovirus infections nor the number of respiratory syncytial virus infections was statistically significant predictors for a more hoarse voice quality. CONCLUSIONS: Based on our results, we would suggest including questions on the presence of respiratory tract infections that have led to hospitalization in the pediatric voice anamnesis. Whether the viral etiology of respiratory tract infections is of importance or not requires further research.

The Resource Burden of Infections With Rhinovirus/Enterovirus, Influenza, and Respiratory Syncytial Virus in Children.

We reviewed the resource utilization of patients with human rhinovirus/enterovirus (HRV/ENT), influenza A/B (FLU), or respiratory syncytial virus (RSV). A total of 2013 patients with nasopharyngeal swabs positive for HRV/ENT, RSV, or FLU were included. Records were reviewed for respiratory support, vascular access procedures, emergency department care only versus admission versus pediatric intensive care unit (PICU) care, antibiotics, length of stay, and billing data. Of the 2013 subjects, 1251 tested positive for HRV/ENT, 558 for RSV, and 204 for FLU. Fewer HRV/ENT patients were discharged from the emergency department ( P < .001); and they were more likely to be admitted to the pediatric intensive care unit ( P < .001). HRV/ENT and RSV patients were more likely to require invasive procedures ( P = .01). Median hospital costs for HRV/ENT patients were more than twice that of FLU patients ( P < .001). HRV/ENT infection in pediatric patients poses a significant resource and cost burden, even when compared with other organisms.

Comparison of the Severity of Respiratory Disease in Children Testing Positive for Enterovirus D68 and Human Rhinovirus.

OBJECTIVE: To compare the characteristics and severity of respiratory disease in children testing positive for enterovirus D68 (EV-D68) and for human rhinovirus (RhV). STUDY DESIGN: A retrospective single center study of children presenting with acute respiratory symptoms and positive polymerase chain reaction for RhV/EV from September 1, 2014 through October 31, 2014 was performed. Specimens were subsequently tested specifically for EV-D68 and specimens identified as RhV were subtyped when possible into RhV-A, RhV-B, and RhV-C species. Clinical manifestations in patients with EV-D68 were compared with those with non-EV-D68, RhV, and RhV-C. RESULTS: Of the 173 patients included in the analysis, 72 tested positive for EV-D68, 61 for RhV, and 30 for RhV-C. There were significantly fewer infants in the EV-D68 group. Patients with EV-D68 were more likely than those without EV-D68, and specifically with RhV-C, to have fever and wheezing. Patients with EV-D68 received more magnesium sulfate for respiratory distress not responding adequately to repeated doses of inhaled albuterol. Hospitalized patients with EV-D68 received more bronchodilator therapy than patients with RhV. Patients with EV-D68 were more likely to be admitted to the intensive care unit and were older than patients without EV-D68. There was no difference in length of overall hospitalization or time in the pediatric intensive care unit. CONCLUSIONS: Children with EV-D68 appeared to have more severe respiratory disease on admission than children with RhV as evidenced by higher rates of fever, wheezing, bronchodilator use and pediatric intensive care unit admission. Despite the initial difference in severity, no significant difference in length of stay was found suggesting that patients with EV-D68 recovered as quickly as other groups.

Outbreak of influenza and rhinovirus co-circulation among unvaccinated recruits, U.S. Coast Guard Training Center Cape May, NJ, 24 July-21 August 2016.

Military and Coast Guard recruits are particularly susceptible to respiratory infections. Although seasonal influenza vaccinations are mandatory for recruits, the vaccine expires annually in June. On 29 July 2016, the U.S. Coast Guard Training Center Cape May, NJ, identified an increase in febrile respiratory illness (FRI) among recruits. During 24 July-21 August, a total of 115 recruits reported symptoms. A total of 74 recruits tested positive for respiratory infections: influenza A (H3) (n=34), rhinovirus (n=28), influenza/rhinovirus co-infection (n=11), and adenovirus/rhinovirus co-infection (n=1), while 41 recruits had no laboratory-confirmed specimen but were considered suspected cases. Only one recruit reported receiving the seasonal influenza vaccine within the previous 12 months. Influenza predominated during 24 July-6 August, whereas rhinovirus predominated during 7 August-20 August. Most (92.2%) cases were identified in four of 10 recruit companies; incidence rates were highest among recruits in weeks 2-4 of an 8-week training cycle. Key factors for outbreak control included rapid detection through routine FRI surveillance, quick decision-making and streamlined response by using a single chain of command, and employing both nonpharmaceutical and pharmaceutical interventions.

[Epidemiological and clinical characteristics of infants admitted to hospital due to human parechovirus infections: A prospective study in Spain]. / Características epidemiológicas y clínicas de los lactantes hospitalizados por infecciones por parechovirus humanos. Estudio prospectivo en España.

INTRODUCTION: Human parechovirus (HPeV) is one of the recently described picornaviridae viruses that have been associated with fever of unknown origin (FUO), clinical sepsis, gastroenteritis, meningitis, or encephalitis in very young infants. The aim of this study is to describe the epidemiology and clinical features of these viruses. PATIENTS AND METHODS: A prospective multicentre 3-year study was conducted in 12 hospitals in Spain. Out of 850 specimens examined, 47 were positive (5.52%), with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae. RESULTS: Out of 850 specimens examined, 47 were positive (5.52%) for HPeV, with HPeV-3 being the most frequent (29 cases). Infections occurred throughout the year, but mainly in May and July, and a biennial distribution was observed. More than half (57%) were neonates, and only 2 children were older than 3 months. Fever was present in all children, with irritability in 45%, rash in 18.6%, and diarrhoea in 14%. The results of biochemical tests were all in normal range. The most common final diagnosis was FUO (61%), followed by clinical sepsis (29%). Up to 29% of infants were admitted to the intensive care unit, but only one patient had sequelae CONCLUSIONS: HPeV circulates in our country, mainly during spring and summer, and affects young infants with a FUO and clinical sepsis. Molecular diagnostic techniques in all hospitals could help in improving the management of patients with these infections.

Severe Parechovirus 3 Infections in Young Infants-Kansas and Missouri, 2014.

BACKGROUND: Infection with parechovirus type 3 (PeV3) can cause severe neurologic and sepsis-like illness in young infants; clinical and epidemiologic descriptions have been limited. We aimed to characterize PeV3 illness and explore risk factors for acquisition in a cluster of neonatal cases at Children's Mercy Hospital in Kansas City, Missouri. METHODS: Cerebrospinal fluid specimens were obtained from infants aged <180 days who were hospitalized with sepsis-like illness or meningitis between June 1 and November 1, 2014. PeV-positive specimens were sequenced at the Centers for Disease Control and Prevention. We reviewed the medical and birth charts of the infants and performed face-to-face parent interviews. We analyzed characteristics according to infant age and intensive care admission status. RESULTS: We identified 35 cases of PeV infection in infants aged 5 to 56 days. Seven infants required intensive care (median age, 11 days vs 27 days among those who did not require intensive care; P = .0044). Six of these 7 infants had neurologic manifestations consistent with seizures, and all 6 of them were treated with acyclovir but subsequently tested negative for herpes simplex virus. Virus sequences formed 2 lineages, both of which were associated with severe illness. Half of the infants were reported to have household contacts who were ill during the week before onset. Infants aged ≤7 days at onset were more likely to have been delivered at the same hospital. CONCLUSIONS: PeV3 can cause severe neurologic illness in neonates, and younger infants are more likely to require intensive care. PeV3 should be considered along with herpes simplex virus and other pathogens when evaluating young infants with sepsis-like illness or meningitis. More widespread testing for PeV3 would enable us to gain a better understanding of the clinical scope and circulation of this virus.

Heated, humidified air for the common cold.

BACKGROUND: Heated, humidified air has long been used by people with the common cold. The theoretical basis is that steam may help congested mucus drain better and that heat may destroy the cold virus as it does in vitro. This is an update of a review last published in 2013. OBJECTIVES: To assess the effects of inhaling heated water vapour (steam) in the treatment of the common cold by comparing symptoms, viral shedding, and nasal resistance. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to February 2017), MEDLINE (1966 to 24 February 2017), Embase (1990 to 24 February 2017), and Current Contents (1998 to 24 February 2017). We also searched World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (8 March 2017) and ClinicalTrials.gov (8 March 2017) as well as reference lists of included studies. SELECTION CRITERIA: Randomised controlled trials using heated water vapour in participants with the common cold or experimentally induced common cold were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Three review authors independently screened titles and abstracts for inclusion of potential studies identified from the search. We recorded the selection process in sufficient detail to complete a PRISMA flow diagram. We used a data collection form for study characteristics and outcome data that was developed and used for previous versions of this review. Two review authors independently extracted data, and a third review author resolved any disagreements. We used Review Manager 5 software to analyse data. MAIN RESULTS: We included six trials from five publications involving a total of 387 participants. We included no new studies in this 2017 update. The 'Risk of bias' assessment suggested an unclear risk of bias in the domain of randomisation and a low risk of bias in performance, detection, attrition, and reporting.It was uncertain whether heated, humidified air provides symptomatic relief for the common cold, as the fixed-effect analysis showed evidence of an effect (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.16 to 0.56; 2 studies, 149 participants), but the random-effects analysis showed no significant difference in the results (OR 0.22, 95% CI 0.03 to 1.95). There is an argument for using either form of analysis. No studies demonstrated an exacerbation of clinical symptom scores. One study conducted in the USA demonstrated worsened nasal resistance, but an earlier Israeli study showed improvement. One study examined viral shedding in nasal washings, finding no significant difference between treatment and placebo groups (OR 0.47, 95% CI 0.04 to 5.19). As judged by the subjective response to therapy (i.e. therapy did not help), the number of participants reporting resolution of symptoms was not significantly higher in the heated humidified group (OR 0.58, 95% CI 0.28 to 1.18; 2 studies, 124 participants). There was significant heterogeneity in the effects of heated, humidified air on different outcomes, therefore we graded the quality of the evidence as low. Some studies reported minor adverse events (including discomfort or irritation of the nose). AUTHORS' CONCLUSIONS: The current evidence does not show any benefits or harms from the use of heated, humidified air delivered via the RhinoTherm device for the treatment of the common cold. There is a need for more double-blind, randomised trials that include standardised treatment modalities.

Rhinovirus and preschool wheeze.

Rhinovirus (RV) known as the common cold virus generally only causes a mild upper respiratory infection, but severe lower respiratory symptoms have been associated with RV infections especially in asthmatic individuals. Wheezing is a symptom of airway obstruction, and preschool children wheezing with RV have been associated with increased risk of asthma at school age. There are, however, conflicting opinions as to whether there are differences in response to RV infection or whether wheezing with RV reveals a preexisting impairment that promotes asthma mainly in predisposed children. The advent of molecular diagnostics to detect respiratory viruses has led to new insights into the role of RV infections. This review will discuss recent information concerning the role of RV as an important respiratory pathogen related to early onset wheeze and exacerbation of established asthma in preschool children.

Single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen.

BACKGROUND: The number of viral pathogens associated with pediatric acute respiratory tract infection (ARI) has grown since the introduction of reverse transcription real-time polymerase chain reaction (RT-PCR) assays. Multiple viruses are detected during a single ARI episode in approximately a quarter of all cases. The clinical relevance of these multiple detections is unclear, as is the role of the individual virus. We therefore investigated the correlation between clinical data and RT-PCR results in children with single- and multiple viral ARI. METHODS: Data from children with ARI were prospectively collected during two winter seasons. RT-PCR testing for 15 viruses was performed in 560 ARI episodes. In the patients with a single-viral etiology, clinical data, laboratory findings, patient management- and outcome data were compared between the different viruses. With this information, we compared data from children of whom RT-PCR data were negative, with children with single- and multiple viral positive results. RESULTS: The viral detection rate was 457/560 (81.6%) of which 331/560 (59.1%) were single infections and 126/560 (22.5%) were multiple infections. In single viral infections, some statistically significant differences in demographics, clinical findings, disease severity and outcome were found between children with different viral etiologies. However, no clinically recognizable pattern was established to be virus-specific. In a multivariate analysis, the only variables that were correlated with longer hospital stay were the use of oxygen and nebulizer therapy, irrespective of the viral pathogen. Children with RT-PCR positive test results had a significant higher disease severity, fever, length of hospital stay, days of extra oxygen supply, and days of antibiotic treatment than children with a negative RT-PCR test result. For children with single- versus children with multiple positive RT-PCR test results, these differences were not significant. CONCLUSIONS: Disease (severity), management and outcome in pediatric ARI are not associated with a specific virus. Single- and multiple viral ARI do not significantly differ with regard to clinical outcome and patient management. For general pediatrics, RT-PCR assays should be restricted to pathogens for which therapy is available or otherwise may have clinical consequences. Further research with an extended panel of RT-PCR assays and a larger number of inclusions is necessary to further validate our findings.

Enterovirus and parechovirus infection in children: a brief overview.

UNLABELLED: Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of enterovirus and parechovirus infection in children. CONCLUSIONS: EV and HPeV infections are a frequent cause of infection in childhood. The clinical presentation is diverse. RT-qPCR is the best way to detect an EV or HPeV. Cerebrospinal fluid, blood and feces have the highest sensitivity for detecting an EV or HPeV. There is no treatment for EV and HPeV infections. Two vaccines against EV 71 are just licensed in China and will be available on the private market. Little is known about the prognosis of EV and HPeV infections. WHAT IS KNOWN: •EV and HPeV are a frequent cause of infection in children. What is new: •This review gives a brief overview over EV and HPeV infection in children.

Human rhinovirus in experimental infection after peroral Lactobacillus rhamnosus GG consumption, a pilot study.

BACKGROUND: Data has emerged on possible beneficial effects of probiotics in respiratory tract viral infections, but it is unclear if the promising positive effects evidenced are due to a reduced viral load during infections. The aims of this work were to investigate the effect of peroral probiotic Lactobacillus rhamnosus GG (American Type Culture Collection [ATCC], Accession No. 53103) consumption on human rhinovirus (HRV) load in nasopharyngeal lavage samples in experimental HRV infection, and to correlate viral load to clinical symptoms. METHODS: Intranasal HRV A39 inoculation was performed on 59 adults, who had consumed juice enriched with live or heat-inactivated L. rhamnosus GG or control juice for 3 weeks prior to inoculation in a randomized, controlled, pilot trial setting. Nasopharyngeal lavage samples and symptom data were analyzed on day 0 before inoculation, and on days 2 and 5. Samples were subjected to quantitative HRV detection by polymerase chain reaction (PCR). RESULTS: Before inoculation 9 of 59 (15%) samples presented with another HRV strain than the studied A39. There was a tendency toward the lowest HRV loads in the L. rhamnosus GG groups and the highest in placebo group (log10 copies/mL, 95% confidence interval [CI], 6.20 [5.18 to 7.40] in live, 6.30 [4.91 to 7.08] in inactivated L. rhamnosus GG, and 7.25 [5.81 to 7.52] in placebo group, p = 0.57 in day 2) in the wild-type excluded population. The HRV load positively correlated with the symptom scores on days 2 and 5 (correlation coefficient 0.61 [p < 0.001] and 0.28 [p = 0.034], respectively). CONCLUSION: Results did not show statistical differences in viral loads in subjects using L. rhamnosus GG when compared to placebo. HRV load positively correlated with the total symptom scores.

Human Parechovirus 3: The Most Common Viral Cause of Meningoencephalitis in Young Infants.

Human parechoviruses (HPeVs) were initially classified as echoviruses. HPeVs occur worldwide, comprising up to 17 genotypes. HPeV1 and HPeV3 are most common. Clinical disease varies somewhat among genotypes. HPeV1 causes mostly gastrointestinal infections. HPeV3's prominence is due to its causing sepsis syndromes and central nervous system (CNS) infections in young infants. Currently, HPeV3 is the most common single cause of aseptic meningitis/meningoencephalitis in infants less than 90 days old in North America, usually with biannual summer-fall seasonality. HPeV3 CNS infections usually lack cerebrospinal fluid pleocytosis. Mortality and sequelae are uncommon, usually accompanying initially severe or neurologically complicated acute illnesses.

Human Memory B Cells Producing Potent Cross-Neutralizing Antibodies against Human Parechovirus: Implications for Prevalence, Treatment, and Diagnosis.

UNLABELLED: The family Picornaviridae is a large and diverse group of positive-sense RNA viruses, including human enteroviruses (EVs) and human parechoviruses (HPeVs). The human immune response against EVs and HPeVs is thought to be mainly humoral, and an insufficient neutralizing antibody (Ab) response during infection is a risk factor and can ultimately be life threatening. The accessibility of different antigenic sites and observed cross-reactivity make HPeVs a good target for development of therapeutic human monoclonal antibodies (MAbs). In this study, we generated two different human MAbs specific for HPeV by screening culture supernatants of Ab-producing human B cell cultures for direct neutralization of HPeV1. Both MAbs showed HPeV1-specific neutralization as well as neutralization of HPeV2. One antibody, AM18, cross-neutralized HPeV4, -5, and -6 and coxsackievirus A9 (CV-A9). VP1 capsid protein-specific assays confirmed that AM18 bound VP1 of HPeV1, -2, and -4 with high affinity (11.5 pM). In contrast, the HPeV1-specific MAb AM28, which neutralized HPeV1 even more efficiently than did AM18, showed no cross-reactivity with HPeV3 to -6 or other EVs and did not bind any of the capsid proteins, suggesting that AM28 is specific for a conformation-dependent, nonlinear epitope on the virus. The discovery of MAbs that are cross-reactive between HPeVs may help development of HPeV treatment options with antibodies and vaccine design based on epitopes recognized by these antibodies. IMPORTANCE: HPeV infections are widespread among young children and adults, causing a broad range of disease. Infections can be severe and life threatening, while no antiviral treatment is available. Given that the absence of neutralizing Abs is a risk factor for severe disease in infants, treatment of picornavirus infections with MAbs would be a therapeutic option. To study antibody neutralization of HPeV in more detail, we generated two different HPeV1-specific human MAbs. Both MAbs show HPeV1-specific neutralization and cross-neutralized HPeV2. One MAb also cross-neutralized other HPeVs. Surprisingly, this MAb also neutralized CV-A9. These MAbs provide a unique tool for further research and for the diagnosis (antigen detection) and possible treatment of HPeV infections.