[Adenovirus-related acute liver failure treated with intravenous immunoglobulin]. / Insuficiencia hepática aguda por adenovirus tratada con inmunoglobulina intravenos.

BACKGROUND: Acute liver failure in pediatric age is a serious multisystem disease, characterized by a failure of the synthesis and detoxification function of the liver. Among the etiologies, viral infection should be investigated. Treatment is supportive and some cases require liver transplantation. CASE REPORT: A 2-year-old girl was admitted for acute liver failure. The PCR viral panel was positive for Adenovirus 41 and IgG antibodies to SARS-CoV-2 were also found. Supportive treatment was started without improvement, so intravenous immunoglobulin was administered, with resolution of the liver failure. CONCLUSIONS: Immunoglobulin has immunomodulatory mechanisms in children with severe acute hepatitis of infectious etiology, so in some cases, its administration can be considered as adjuvant therapy.

ANTECEDENTES: La insuficiencia hepática aguda en pacientes pediátricos es una enfermedad multisistémica grave, caracterizada por falla de la función de síntesis y detoxificación del hígado. Dentro de su origen debe investigarse alguna infección viral. El tratamiento es de soporte y algunos casos requieren trasplante hepático. REPORTE DE CASO: Paciente pediátrica de 2 años, que ingresó al servicio médico por insuficiencia hepática aguda. El panel viral por PCR fue positivo para adenovirus 41 y anticuerpos IgG para SARS-CoV-2. Se inicio tratamiento de soporte sin reacción satisfactoria, por lo que se administró inmunoglobulina intravenosa, con resultados adecuados y curación de la insuficiencia hepática. CONCLUSIONES: La inmunoglobulina tiene mecanismos inmunomoduladores en pacientes pediátricos con hepatitis aguda grave de origen infeccioso, por lo que en algunos casos puede considerase su administración como terapia adyuvante.

Epidemiology and molecular detection of human adenovirus and non-polio enterovirus in fecal samples of children with acute gastroenteritis: A five-year surveillance in northern Brazil.

Acute gastroenteritis (AGE) is a common pediatric infection that remains a significant cause of childhood morbidity and mortality worldwide, especially in low-income regions. Thus, the objective of this study was to detect human adenovirus (HAdV) and non-polio enterovirus (NPEV) in fecal samples from the Gastroenteritis Surveillance Network, and to identify circulating strains by nucleotide sequencing. A total of 801 fecal samples were tested using qPCR/RT-qPCR, and 657 (82.0%) were inoculated into HEp-2C and RD cell lines. The HAdV and NPEV positivity rates obtained using qPCR/RT-qPCR were 31.7% (254/801) and 10.5% (84/801), respectively, with 5.4% (43/801) co-detection. Cytopathic effect was observed in 9.6% (63/657) of patients, 2.7% (18/657) associated with HAdV, and 6.2% (41/657) associated with NPEV after testing by ICC-PCR. A comparison of the two methodologies demonstrated an agreement of 93.5% for EVNP and 64.4% for HAdV. These two viruses were detected throughout the study period, with HAdV positivity rates ranging from 41% in Amapá to 18% in Pará. The NEPV varied from 18% in Pará/Rondônia to 3% in Acre. The most affected age group was over 60 months for both HAdV and NPEV. Samples previously positive for rotavirus and norovirus, which did not show a major difference in the presence or absence of diarrhea, fever, and vomiting, were excluded from the clinical analyses of these two viruses. These viruses circulated over five years, with a few months of absence, mainly during the months corresponding to the waves of SARS-CoV-2 infection in Brazil. Five HAdV species were identified (A, B, C, D, and F), with a greater predominance of HAdV-F41 (56.5%) followed by HAdV-C (15.2%). Three NPEV species (A, B, and C) were detected, with serotypes E14 (19.3%) and CVA-24 (16.1%) being the most prevalent. The present study revealed a high diversity of NPEV and HAdV types circulating in children with AGE symptoms in the northern region of Brazil.

Adenovirus 36 seropositivity is related to the expression of anti-adipogenic lncRNAs GAS5 and MEG3 in adipose tissue obtained from subjects with obesity.

BACKGROUND: Human Adenovirus D-36 (HAdV-D36) promotes adipogenesis in cellular and animal models and may contribute to the development of human obesity. Induction of PPARγ by HAdV-D36 seems to have a central role in the maintenance of adipogenic status. There is limited information about epigenetic mechanisms contributing to this process in human adipose tissue. This study evaluated the expression of lncRNAs (ADINR, GAS5 and MEG3) and miRNAs (miR-18a and miR-140) involved in the adipogenic process in visceral adipose tissue (VAT) of subjects with obesity with previous HAdV-D36 infection (seropositive) and unexposed (seronegative) subjects with obesity. METHODS: Individuals with obesity were grouped according to the presence of antibodies against HAdV-D36 (Seropositive: HAdV-D36[+], n = 29; and Seronegative: HAdV-D36[-], n = 28). Additionally, a group of individuals without obesity (n = 17) was selected as a control group. The HAdV-D36 serology was carried out by ELISA. Biopsies of VAT were obtained during an elective and clinically indicated surgery (bariatric or cholecystectomy). RNA extraction from VAT was performed and the expression of PPARG and non-coding RNAs was evaluated by qPCR. RESULTS: HAdV-D36[+] individuals had lower expression of anti-adipogenic lncRNAs GAS5 (p = 0.016) and MEG3 (p = 0.035) compared with HAdV-D36[-] subjects with obesity. HAdV-D36[+] subjects also presented increased expression of the adipogenic miRNA miR-18a (p = 0.042), which has been reported to be modulated by GAS5 through a RNA sponging mechanism during adipogenic differentiation. Additionally, an inverse correlation of GAS5 with PPARG expression was observed (r = -0.917, p = 0.01). CONCLUSION: Our results suggest that HAdV-D36 is related to non-coding RNAs implicated in adipogenesis, representing a potential mechanism by which previous HAdV-D36 infection could be associated with the long-term maintenance of adipogenic status, probably through the GAS5/miR-18a axis.

Influence of Seropositivity against Adenovirus-36 on the Risk of Obesity and Insulin Resistance in the Child Population of Southern Chile.

Background: Previous infection with Adenovirus-36 (HAdv-D36) has been associated with adipogenesis and glycemic regulation in cell culture and animal models. In humans, HAdv-D36 antibodies correlate with increased obesity risk yet paradoxically enhance glycemic control across various demographics. This study assesses the association of HAdv-D36 seropositivity with obesity, lipid, and glycemic profiles among school-aged children. Methods: We evaluated 208 children aged 9-13, categorized by BMI z-scores into normal weight (-1 to +1), overweight (+1 to +2), and obese (>+3). Assessments included anthropometry, Tanner stage for pubertal development, and biochemical tests (relating to lipids, glucose, and insulin), alongside HAdv-D36 seropositivity checked via ELISA. Insulin resistance was gauged using Chilean pediatric criteria. Results: The cohort displayed a high prevalence of overweight/obesity. HAdv-D36 seropositivity was 5.4%, showing no correlation with nutritional status. Additionally, no link between HAdv-D36 seropositivity and lipid levels was observed. Notably, insulin levels and HOMA-RI were significantly lower in HAdv-D36 positive children (p < 0.001). No cases of insulin resistance were reported in the HAdv-D36 (+) group in our population. Conclusions: HAdv-D36 seropositivity appears to decrease insulin secretion and resistance, aligning with earlier findings. However, no association with obesity development was found in the child population of southern Chile.

An Observational Study Suggests That Natural HAdV-36 Infection Decreases Blood Glucose Levels without Affecting Insulin Levels in Obese Young Subjects.

Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects). All participants underwent assessments for anthropometry, blood pressure, circulating fasting levels of glucose, lipids, insulin, and anti-HAdV-36 antibodies; additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. In all, 57.17% of the subjects were HAdV-36 seropositive. Moreover, HAdV-36 seroprevalence was higher in obese subjects compared to their normal weight counterparts (59% vs. 55%). BMI (33.1 vs. 32.3 kg/m2, p = 0.03), and waist circumference (107 vs. 104 cm, p = 0.02), insulin levels (21 vs. 16.3 µU/mL, p = 0.003), and HOMA-IR (4.6 vs. 3.9, p = 0.02) were higher in HAdV-36-positive subjects with obesity compared to seronegative subjects. In the obese group, HAdV-36 seropositivity was associated with a reducing effect in blood glucose levels in a model adjusted for total cholesterol, triglyceride levels, age and sex (ß = -10.44, p = 0.014). Furthermore, a statistically significant positive relationship was observed between HAdV-36 seropositivity and insulin levels in the obesity group. These findings suggest that natural HAdV-36 infection improves glycemic control but does not ameliorate hyperinsulinemia in obese subjects.

Fecal leukocyte frequency in children with acute viral gastroenteritis: a single-center experience.

OBJECTIVE: Our objective was to determine the frequency of rotavirus, adenovirus, and rota-adenovirus co-infections and investigate the fecal leukocyte rate associated with these infections in patients with gastroenteritis. METHODS: This is a retrospective study. We identified patients who were admitted to the pediatric emergency department with acute gastroenteritis and had their stool samples tested for rotavirus and/or adenovirus antigens. Among them, we determined the individuals who underwent stool microscopy tests on the same day and recorded their results. RESULTS: A total of 1,577 patients who underwent testing for rotavirus and/or adenovirus antigens in their stool samples were identified. Among these patients, 583 individuals had concurrent fecal microscopy results. The prevalence of solely rotavirus antigen positivity was 16.4%, solely adenovirus antigen positivity was 2.9%, and rota-adenovirus co-infections were detected in 1.8% of the children. The fecal leukocyte rates in children infected with rotavirus, adenovirus, and rota-adenovirus co-infections were 4.8, 13.3, and 88.9%, respectively. CONCLUSION: The presence of fecal leukocytes was detected at a high rate in cases of viral gastroenteritis, especially in rota-adenovirus co-infections. Therefore, clinicians should not consider only bacterial pathogens in the presence of fecal leukocytes.

Severe adenovirus infection outbreak in Colombia: Experience from a tertiary pediatric hospital in 2022. / Brote de adenovirus grave en Colombia: experiencia de un hospital pediátrico de tercer nivel en 2022

Introduction. During the SARS-CoV-2 pandemic, many countries experienced decreased respiratory virus circulation, followed by an out-of-season outbreak. In a pediatric hospital in Colombia, we observed a surge in severe adenovirus infections, leading to concerns about the impact of eased public health restrictions and immune debt in children under five years old. Objective. To describe the clinical characteristics of patients with severe adenovirus infection in a pediatric hospital in Colombia. Materials and methods. We reviewed the data of 227 patients with severe adenovirus infection at the Fundación Hospital Pediátrico La Misericordia. Results. A total of 196 patients were included in this study. The median age was two years, and 62% were male. Adenoviruses were isolated from all patients' samples. Ninetyseven percent were admitted to the pediatric intensive care unit, 94% required respiratory support, and the in-hospital lethality rate was 11%. Conclusion. In 2022, there was an outbreak of severe adenovirus infections, affecting mainly children under five years of age, with higher-than-usual mortality.

Introducción. Durante la pandemia por SARS-CoV-2, muchos países evidenciaron una disminución en la circulación de virus respiratorios, seguida por un brote fuera de la temporada esperada. En un hospital de Colombia, se observó un aumento en los casos de infección grave por adenovirus, lo cual generó preocupación sobre el impacto que tuvo la disminución de los cuidados establecidos durante pandemia y la posible deuda inmunológica en niños menores de cinco años. Objetivo. Describir las características clínicas de los pacientes con infección grave por adenovirus en un hospital pediátrico de Colombia. Materiales y métodos. Se revisaron 227 pacientes con infección grave por adenovirus en la Fundación Hospital Pediátrico La Misericordia, desde el 1° de enero hasta el 31 de diciembre de 2022. Resultados. El estudio incluyó 196 casos. La edad media de los pacientes fue de dos años y el 62 % eran de sexo masculino. Los adenovirus se aislaron a partir de las muestras de todos los pacientes. El 97 % de los pacientes ingresó a la unidad de cuidados intensivos, el 94 % requirió soporte ventilatorio y la tasa de mortalidad fue del 11 %. Conclusiones. En el 2022 hubo un brote de adenovirus que afectó principalmente a los niños menores de cinco años, con una mortalidad mayor a lo reportado con anterioridad en Colombia.

Adipocyte commitment of 3T3-L1 cells is required to support human adenovirus 36 productive replication concurrent with altered lipid and glucose metabolism.

Human adenovirus 36 (HAdV-D36) can cause obesity in animal models, induces an adipogenic effect and increased adipocyte differentiation in cell culture. HAdV-D36 infection alters gene expression and the metabolism of the infected cells resulting in increased glucose internalization and triglyceride accumulation. Although HAdV-D36 prevalence correlates with obesity in humans, whether human preadipocytes may be targeted in vivo has not been determined and metabolic reprogramming of preadipocytes has not been explored in the context of the viral replication cycle. HAdV-D36 infection of the mouse fibroblasts, 3T3-L1 cells, which can differentiate into adipocytes, promotes proliferation and differentiation, but replication of the virus in these cells is abortive as indicated by short-lived transient expression of viral mRNA and a progressive loss of viral DNA. Therefore, we have evaluated whether a productive viral replication cycle can be established in the 3T3-L1 preadipocyte model under conditions that drive the cell differentiation process. For this purpose, viral mRNA levels and viral DNA replication were measured by RT-qPCR and qPCR, respectively, and viral progeny production was determined by plaque assay. The lipogenic effect of infection was evaluated with Oil Red O (ORO) staining, and expression of genes that control lipid and glucose metabolism was measured by RT-qPCR. In the context of a viral productive cycle, HAdV-D36 modulated the expression of the adipogenic genes, C/EBPα, C/EBPß and PPARγ, as well as intracellular lipid accumulation, and the infection was accompanied by altered expression of glucolytic genes. The results show that only adipocyte-committed 3T3-L1 cells are permissive for the expression of early and late viral mRNAs, as well as viral DNA replication and progeny production, supporting productive HAdV-D36 viral replication, indicating that a greater effect on adipogenesis occurs in adipocytes that support productive viral replication.

Enteric adenovirus epidemiology from historical fecal samples in Brazil (1998-2005): Pre-rotavirus vaccine era.

Human adenovirus (HAdV) is recognized as frequent cause of acute gastroenteritis and enteric viruses can be preserved in frozen stored feces for long periods of times. The purpose of the present study was to investigate enteric HAdV genotypic diversity in archival fecal specimens stored from 1998 to 2005 in order to understand the natural history of HAdV in diarrheal patients in Brazil before rotavirus vaccine introduction. A total of 3346 specimens were tested for HAdV using conventional PCR. Genotypes were identified by sequencing. HAdV was detected in 6.8% (228/3346). Positivity was higher in children ≤ 5 years and males (p < 0.05). HAdV was most frequently observed during winter and spring seasons (p < 0.05). HAdV-F41 was the most prevalent genotype (59.2%;135/228), followed by HAdV-F40 (16.2%;37/228), HAdV-C1 (5.2%;12/228), HAdV-C2 (5.2%;12/228), HAdV-C5 (3.1%;7/228), HAdV-A12 (1.3%;3/228), HAdV-E4 (0.9%;2/228), HAdV-B3 (0.9%;2/228) and HAdV-B21 (0.4%;1/228). In 7.6% (17/228) only species D could be defined. HAdV-E4 strains were phylogenetic analyzed and classified as lineage (a)-like PG II. HAdV prevalence remained stable in Brazilian population, regardless rotavirus vaccine introduction. The predominant HAdV genotypes detected did not change over time, highlighting a high diversity of circulating strains in the country throughout decades. Due to the historical lack of HAdV genotyping surveillance in Brazil, HAdV-E4 epidemiology is virtually unknown in the country. The present study contributed significantly to the understanding of the natural history of HAdV in diarrheal patients in Brazil. The acquired data are important for clinical diagnosis, particularly for studies investigating enteric viruses' prevalence and molecular epidemiology of archival clinical specimens.

Epidemiology of enteric virus infections in children living in the Amazon region.

OBJECTIVES: To verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix™ vaccination coverage in children from the Amazon region. DESIGN: Fecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix™ RVA vaccination data were recorded. RESULTS: Norovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0-2.3; P = 0.04) but not to RVA, norovirus or SaV infection. CONCLUSIONS: Norovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene.

Epidemiology and factors associated with the severity of viral acute lower respiratory infection in children hospitalized in Manaus, Amazonas, in 2017-2018: An observational study.

ABSTRACT: To investigate the epidemiology and factors associated with the severity of viral acute lower respiratory infection (ALRI) in children hospitalized in Manaus, Amazonas, in 2017 to 2018.Retrospective cohort study of children hospitalized at the Hospital and Emergency Room Delphina Rinaldi Abdel Aziz, in Manaus, from April 01, 2017 to August 31, 2018, with a clinical diagnosis of ALRI and nasopharyngeal aspirates positive for at least 1 respiratory virus.One hundred forty-six children aged 0.2 to 66 months (median 7 months) were included. Patients were divided into 2 groups according to the disease severity classified by an adapted Walsh et al score: moderate disease, score 0-4, n = 66 (45.2%) and severe disease, score 5-7, n = 80 (54.8%). A greater number of viral ALRI cases were observed in the rainiest months. Respiratory syncytial virus was the most prevalent (n = 103, 70.3%), followed by metapneumovirus (n = 24, 16.4%), influenza virus (n = 17, 11.6%), parainfluenza virus (n = 11, 7.5%), and adenovirus (n = 4, 2.7%). Co-detections of 2 to 3 viruses were found in 12 (8.2%) patients. The presence of viral coinfection was an independent risk factor for disease severity (adjusted relative risk [RR] 1.53; 95% CI 1.10-2.14). Twelve patients (8.2%) died, all with severe disease. Risk factors for death were shock (adjusted RR 10.09; 95% CI 2.31-43.90) and need for vasoactive drugs (adjusted RR 10.63; 95% CI 2.44-46.31).There was a higher incidence of viral ALRI in Manaus in the rainy season. Respiratory syncytial virus was the most prevalent virus. The presence of viral coinfection was an independent risk factor for disease severity.

Genotypes and phylogenetic analysis of adenovirus in children with respiratory infection in Buenos Aires, Argentina (2000-2018).

Human adenoviruses (HAdV) are one of the most frequent causes of respiratory infections around the world, causing mild to severe disease. In Argentina, many studies focused on the association of HAdV respiratory infection with severe disease and fatal outcomes leading to the discovery in 1984 of a genomic variant 7h associated with high fatality. Although several molecular studies reported the presence of at least 4 HAdV species (B, C, D and E) in Argentina, few sequences were available in the databases. In this study, sequences from the hexon gene region were obtained from 141 patients as a first approach to assess the genetic diversity of HAdVs circulating in Buenos Aires, Argentina. Phylogenetic analysis of these sequences and others recovered from public databases confirmed the circulation of the four above-mentioned species represented by 11 genotypes, with predominance in species B and C and shifts in their proportion in the studied period (2000 to 2018). The variants detected in Argentina, for most of the genotypes, were similar to those already described in other countries. However, uncommon lineages belonging to genotypes C2, C5 and E4 were detected, which might indicate the circulation of local variants and will deserve further studies of whole-genome sequences.

Adenovirus-36 as one of the causes of obesity: the review of the pathophysiology.

The dramatic increase of people affected by obesity worldwide seems to be influenced by external factors independent of eating habits, physical exercise, or genetic characteristics. There may be a number of such factors, but one hypothesis is that there is person-to-person transmission, causing an epidemic effect, as occurs with infectious diseases. In animal models, experimental infection with human adenovirus-36 (Adv36) causes obesity. Humans cannot be experimentally infected, but a number of studies found a correlation of positive serology for Adv36 with overweight/obesity in humans. In vitro studies have shown that Adv36 accelerates the differentiation and proliferation of preadipocytes into adipocytes and increases their lipid concentration. Another viral mechanism involved is the activation of a noninsulin-dependent process that increases glucose uptake, mainly in adipose tissue and muscle. The increased glucose, coupled with increased lipogenesis due to increased fatty acid synthase and the action of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in stimulating adipocyte differentiation from adult stem cells enhances fat accumulation within the adipocytes. In studies conducted to date, the Adv36 E4 open reading frame 1 gene (E4orf1), which activates the glucose transporter protein isoform 4 (GLUT4) and glucose transporter protein isoform 1 (GLUT1) glucose transporters, appears to play a major role in the virus adipogenesis. The aim of this study was to review the pathophysiology of obesity and the role of Adv36.

Diversity of enteric and non-enteric human adenovirus strains in Brazil, 2006-2011.

During 2006-2011, 5035 fecal samples were tested by PCR for human adenovirus (HAdV) and sequenced. HAdV was detected in 198 cases (3.9%), with the highest rate in children ≤ 5 years. Enteric HAdVs were the most prevalent genotypes (78%; 146/187): HAdV-F41 (63.6%; 119/187), HAdV-F40 (12.3%; 23/187), HAdV-A12 (1.6%; 3/187) and HAdV-A31 (0.5%; 1/187). Non-enteric HAdVs were detected in 22% (41/187): HAdV-C1 (8.0%; 15/187), HAdV-C2 (6.9%; 13/187), HAdV-C5 (4.3%; 8/187), HAdV-D8 (1.3%; 2/187), HAdV-B21 (0.5%; 1/187), HAdV-B3 (0.5%; 1/187) and HAdV-C6 (0.5%; 1/187). This 6-year retrospective study points out a high diversity of HAdV types circulating in Brazil and highlights the need to carry out molecular epidemiological studies of HAdV among patients with acute diarrheal infection on a regular basis.

Epidemiology of human adenovirus associated with respiratory infection in southern Brazil.

Human adenoviruses (HAdVs) are associated with respiratory infection in the human population worldwide, but HAdV is underreported and less studied than other respiratory viruses. We investigated HAdV in patients with respiratory infection in Rio Grande do Sul (RS), Brazil, between 2004 and 2018. The frequency and seasonality of HAdV, clinical symptoms and underlying diseases were analysed. Respiratory samples from outpatients with acute respiratory illness (ARI) who attended sentinel units and from inpatients with severe acute respiratory infection (SARI) were collected for HAdV detection by immunofluorescence assay; demographic and clinical data were analysed. In total, 43,514 cases of respiratory infection were analysed, of which 8,901 were ARI (20.5%), and 34,613 (79.5%) were SARI. Respiratory viruses were detected in 35.8% of the cases. The frequency of HAdV in relation to respiratory viruses was 2.8%. HAdV circulated year-round, with higher frequency during winter and early spring; increases in the average monthly temperature were associated with decreases in HAdV infections (p = 0.013). Most hospitalized patients with HAdV were male (p = 0.003). HAdV infection showed association with age (p < 0.001), and children between 1 and 5 years old accounted for 30.8% of the outpatients, whereas among cases of SARI, 88.2% were paediatric patients. Among inpatients with HAdV, 3% died, and of these, the majority had at least one underlying condition, such as cardiopathy and immunosuppression. HAdV infection of the respiratory tract causes morbidity and mortality, and individuals with heart diseases and the immunocompromised are at higher risk of fatality.

Viral gastroenteritis in Tocantins, Brazil: characterizing the diversity of human adenovirus F through next-generation sequencing and bioinformatics.

Human enteric adenovirus species F (HAdV-F) is one of the most common pathogens responsible for acute gastroenteritis worldwide. Brazil is a country with continental dimensions where continuous multiregional surveillance is vital to establish a more complete picture of the epidemiology of HAdV-F. The aim of the current study was to investigate the molecular epidemiology of HAdV-F using full-genome data in rural and low-income urban areas in northern Brazil. This will allow a genetic comparison between Brazilian and global HAdV-F strains. The frequency of HAdV-F infections in patients with gastroenteritis and molecular typing of positive samples within this period was also analysed. A total of 251 stool samples collected between 2010 and 2016 from patients with acute gastroenteritis were screened for HAdV-F using next-generation sequencing techniques. HAdV-F infection was detected in 57.8 % (145/251) of samples. A total of 137 positive samples belonged to HAdV-F41 and 7 to HAdV-F40. HAdV-F40/41 dual infection was found in one sample. Detection rates did not vary significantly according to the year. Single HAdV-F infections were detected in 21.9 % (55/251) of samples and mixed infections in 37.4 % (94/251), with RVA/HAdV-F being the most frequent association (21.5 %; 54/251). Genetic analysis indicated that the HAdV-F strains circulating in Brazil were closely related to worldwide strains, and the existence of some temporal order was not observed. This is the first large-scale HAdV-F study in Brazil in which whole-genome data and DNA sequence analyses were used to characterize HAdV-F strains. Expanding the viral genome database could improve overall genotyping success and assist the National Center for Biotechnology Information (NCBI)/GenBank in standardizing the HAdV genome records by providing a large set of annotated HAdV-F genomes.

Pediatric Asthma Health Care Utilization, Viral Testing, and Air Pollution Changes During the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused dramatic changes in daily routines and health care utilization and delivery patterns in the United States. Understanding the influence of these changes and associated public health interventions on asthma care is important to determine effects on patient outcomes and identify measures that will ensure optimal future health care delivery. OBJECTIVE: We sought to identify changes in pediatric asthma-related health care utilization, respiratory viral testing, and air pollution during the COVID-19 pandemic. METHODS: For the time period January 17 to May 17, 2015 to 2020, asthma-related encounters and weekly summaries of respiratory viral testing data were extracted from Children's Hospital of Philadelphia electronic health records, and pollution data for 4 criteria air pollutants were extracted from AirNow. Changes in encounter characteristics, viral testing patterns, and air pollution before and after Mar 17, 2020, the date public health interventions to limit viral transmission were enacted in Philadelphia, were assessed and compared with data from 2015 to 2019 as a historical reference. RESULTS: After March 17, 2020, in-person asthma encounters decreased by 87% (outpatient) and 84% (emergency + inpatient). Video telemedicine, which was not previously available, became the most highly used asthma encounter modality (61% of all visits), and telephone encounters increased by 19%. Concurrently, asthma-related systemic steroid prescriptions and frequency of rhinovirus test positivity decreased, although air pollution levels did not substantially change, compared with historical trends. CONCLUSIONS: The COVID-19 pandemic in Philadelphia was accompanied by changes in pediatric asthma health care delivery patterns, including reduced admissions and systemic steroid prescriptions. Reduced rhinovirus infections may have contributed to these patterns.

Genomic Analyses of Potential Novel Recombinant Human Adenovirus C in Brazil.

Human Adenovirus species C (HAdV-C) is the most common etiologic agent of respiratory disease. In the present study, we characterized the nearly full-length genome of one potential new HAdV-C recombinant strain constituted by Penton and Fiber proteins belonging to type 89 and a chimeric Hexon protein of types 1 and 89. By using viral metagenomics techniques, we screened out, in the states of Tocantins and Pará, Northern and North regions of Brazil, from 2010 to 2016, 251 fecal samples of children between 0.5 to 2.5 years old. These children were presenting acute diarrhea not associated with common pathogens (i.e., rotavirus, norovirus). We identified two HAdV-C strains in two distinct patients. Phylogenetic analysis performed using all complete genomes available at GenBank database indicated that one strain (HAdV-C BR-245) belonged to type 1. The phylogenetic analysis also indicated that the second strain (HAdV-C BR-211) was located at the base of the clade formed by the newly HAdV-C strains type 89. Recombination analysis revealed that strain HAdV-C BR-211 is a chimera in which the variable regions of Hexon gene combined HAdV-C1 and HAdV-C89 sequences. Therefore, HAdV-C BR-211 strain possesses a genomic backbone of type HAdV-C89 and a unique insertion of HAdV-C1 in the Hexon sequence. Recombination may play an important driving force in HAdV-C diversity and evolution. Studies employing complete genomic sequencing on circulating HAdV-C strains in Brazil are needed to understand the clinical significance of the presented data.