HAdV Infection Research Articles

Molecular Characterization of Human Adenoviruses Associated with Pediatric Respiratory Infections in Omdurman, Sudan

Acute respiratory viral infection (ARVI) is a common cause of morbidity and mortality especially in pediatric patients. Among important respiratory pathogens are adenoviruses, The illnesses can range from the common cold to pneumonia Depending on the type, adenoviruses can cause other illnesses such as gastroenteritis, conjunctivitis, cystitis, and, less commonly, neurological disease. Aim of study: molecular detection of respiratory infection due to adenovirus among children in Khartoum state. Respiratory specimens were collected from children’s patients with RTIs in the emergency department Mohamed Alamin Hamid pediatric hospital Omdurman in Khartoum state during the period of October 2022 to February 2023.the HAdV infection were determined by PCR technique. A total of 50 nasal swap were investigated for HAdV, throughout th PCR technique by using specific primer. The results showed 18 (36.0%) were positive and 32 (64.0%) were negative for HAdVs. The statistical analysis revealed no significant difference between age groups (X2= 0.786 P. value: 0.375). This study summarized the HAdV were the predominant types identified in children less than five years intend to have respiratory tract infection according to clinical symptoms of upper or lower respiratory infections.by using conventional PCR for identify with highly sensitively.

Immune reconstitution and cidofovir administration rescue human adenovirus hepatitis after allogeneic hematopoietic cell transplantation

Human adenovirus infection (HAdV) may be fatal in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cidofovir is effective in only a part of the post-HCT HAdV infection. Therefore, posttransplant immune reconstitution is important for HAdV clearance. We describe the detailed immune reconstitution and response of adenovirus-specific T cells in a patient with inborn errors of immunity who had disseminated HAdV infection with hepatitis post-HCT and was treated with cidofovir.Though the patient received cidofovir for only 19 days starting from Day 72 after HCT because of renal dysfunction, we observed T-cell reconstitution, a decrease in HAdV copy number, and amelioration of the symptoms of HAdV infection after Day 90. We initially observed expanded NK and CD8+CD45RO+ memory subsets and later gradual increase of naïve T cells eveloped after cessation of cidofovir treatment. An increase in adenovirus-specific IFN-γ secretion from 2 to 4 months after HCT was confirmed by ELISpot assay.The progression of immune reconstitution and cidofovir treatment are considered to have contributed to survival in this patient. Optimization of transplantation methods, prompt appropriate antiviral medication, and virus-specific T-cell therapy would be necessary as the better strategy for systemic HAdV infection.

Retrospective analysis of hospital electronic health records reveals unseen cases of acute hepatitis with unknown aetiology in adults in Oxfordshire

BackgroundAn outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other ‘helper viruses’, including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data captured by electronic health records (EHR).MethodsWe used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016–2022, for all ages from 18 months and older. We investigated clinical characteristics and temporal distribution of presentations of acute hepatitis and of adenovirus infections based on laboratory data and clinical coding. We relaxed the stringent case definition adopted during the AS-Hep-UA to identify all cases of acute hepatitis with unknown aetiology (termed AHUA). We compared events within the outbreak period (defined as 1st Oct 2021—31 Aug 2022) to the rest of our study period.ResultsOver the study period, there were 903,433 acute presentations overall, of which 391 (0.04%) were classified as AHUA. AHUA episodes had significantly higher critical care admission rates (p < 0.0001, OR = 41.7, 95% CI:26.3–65.0) and longer inpatient admissions (p < 0.0001) compared with the rest of the patient population. During the outbreak period, significantly more adults (≥ 16 years) were diagnosed with AHUA (p < 0.0001, OR = 3.01, 95% CI: 2.20–4.12), and there were significantly more human adenovirus (HadV) infections in children (p < 0.001, OR = 1.78, 95% CI:1.27–2.47). There were also more HAdV tests performed during the outbreak (p < 0.0001, OR = 1.27, 95% CI:1.17–1.37). Among 3,707 individuals who were tested for HAdV, 179 (4.8%) were positive. However, there was no evidence of more acute hepatitis or increased severity of illness in HadV-positive compared to negative cases.ConclusionsOur results highlight an increase in AHUA in adults coinciding with the period of the outbreak in children, but not linked to documented HAdV infection. Tracking changes in routinely collected clinical data through EHR could be used to support outbreak surveillance.

Pathogenesis diagnosis of a pediatric patient suffering from multi-organ abscesses

A pediatric patient suffered from renal and hepatic abscesses (through hepatorenal space) and recovered by antibiotics and other therapies. By clinical analysis, the multi-organ abscesses might be caused by bloodstream-disseminated infection. In order to identify the pathogen, we collected kidney biopsy tissue, swabs, and plasma samples, and used metagenomics next-generation sequencing (mNGS) and some traditional methods. The results revealed that polymicrobial especially anaerobic bacteremia (Bacteroides fragilis, et al.) contributed to the abscess formation. What is more, systematic human adenovirus C (HAdV-C) infection was shown, and the virus was isolated. The titer of HAdV-2 neutralizing antibodies was 1/4 in the plasma after symptoms onset. Although the exact mechanism of HAdV-2 infection in multiple abscess formation has not been clarified, the case of multi-organ abscesses in the context of polymicrobial especially anaerobic bacteremia and HAdV infection in healthy children is infrequent.

Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir.

human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

Surveillance and epidemiological characterization of human adenovirus infections among outpatient children with acute gastroenteritis during the COVID-19 epidemic in Shanghai, China

BackgroundHuman adenovirus (HAdV) has been recognized as one of the common enteric viruses associated with acute gastroenteritis (AGE) in children. The aim of this study was carried out to illustrate the epidemiological characterization of HAdV Infections among children younger than 15 years in Shanghai during COVID-19.MethodsDuring May 2020 and April 2022, 1048 fecal samples were collected from children ≤ 15 years diagnosed with AGE in the Children’s Hospital of Fudan University. HAdV was identified by PCR and sequenced with specific primers. All the obtained sequences were analyzed by MEGA (version 6.0). Demographic information and clinical features data were also collected and analyzed.ResultsIn total, 97 (9.3%, 97/1048) samples were detected to be HAdV during May 2020 and April 2022. We found an atypical upsurge in HAdV infection in the year 2021 after a major suppression in the year 2020. Approximately 84.5% (82/97) of HAdV-infected children were aged 0–60 months. Among the 97 HAdV-positive samples, only two species and five genotypes were detected. HAdV-F (88.7%, 86/97) was the most prevalent species and HAdV-F41 (87.6%, 85/97) was the most common genotype. Diarrhea, vomiting, and fever were the main clinical manifestations in children infected with HAdV. The children aged from 0 to 12 months showed simpler patterns of clinical presentation than those of children older than 13 months.ConclusionsOur findings described the epidemiological changes of HAdV infection in children with AGE during the COVID-19, which further underscored the importance of continuous surveillance of HAdV at both local and global scales.

Fecal rotavirus and adenovirus antigen detection and clinical analysis of children with acute gastroenteritis in a hospital of Beijing City from 2019 to 2022

As a single-center retrospective study, we analyzed the results of rotavirus and human adenovirus antigens in stool samples with colloidal gold immunochromatography method in children with acute gastroenteritis under the age of five who were treated in our hospital from 2019 to 2022. After excluding nonconforming cases and duplicate cases, 2 896 cases were included, of which 559 cases were detected with at least one viral antigen. According to the test results, they were divided into RV positive group, HAdV positive group and RV & HAdV double positive group. The gender, age, seasonal distribution, clinical symptoms and related laboratory tests were compared and analyzed with χ2 test, analysis of variance and nonparametric test. Among the single samples from 2 896 children, the positive rate of RV antigen was 6.21% (180/2 896), the positive rate of HAdV antigen was 10.91% (316/2 896), and the double positive rate of RV & HAdV was 2.18% (63/2 896). The positive rate of HAdV antigen in 2021 was 16.11%, a significant increase compared with 6.20% in 2020. RV infection has obvious seasonality, and spring and winter are the seasons with high incidence of infection (χ2=74.018, P<0.001), while HAdV infection has no obvious seasonality (χ2=2.110, P=0.550), showing sporadic infection throughout the year. The proportions of fever and vomiting symptoms in children with RV infection were significantly higher than those in the HAdV infection group (χ2=40.401, P<0.001; χ2=32.593, P<0.001), but the positive rate of white blood cells in the stool was significantly lower than that in the HAdV infection group (χ2=13.741,P<0.01). In summary, paying attention to the epidemiological changes of RV and HAdV is of great significance for clinical diagnosis and treatment and disease prevention and control.

Monocyte count is associated with the severity of human adenovirus pneumonia in hospitalized children aged less than 6 years

BackgroundHuman Adenovirus (HAdV) pneumonia is common in young children and infants. Overall, 7–8% of all viral respiratory illnesses among children for less than 5 years are induced by HAdVs. Unfortunately little is known about the role of monocyte count in the disease severity.MethodsData were gathered from 595 children (age < 6 years) who were diagnosed with HAdV infection at the 1st People's Hospital (Changde City, China) between January 2019 and December 2019. There were 181 cases of severe adenovirus pneumonia.ResultsThe correlation between the patients' monocyte count and the severity of HAdV pneumonia was estimated by performing a multiple linear regression analysis. The results showed a negative association (OR: 0.53, 95% CI 0.31 to 0.89, P < 0.05). We further built Generalized Additive Models (GAMs) and demonstrated that the monocyte count had a non-linear association with severe HAdV pneumonia. The inflection point of monocyte count detected in the two-stage linear regression model was 1.5. On the left side of this point, the monocyte count was negatively interrelated (OR: 0.26, 95% CI 0.13 to 0.52, P < 0.001), while on the opposite side, there was a positive association (OR: 7.48, 95% CI 1.30 to 43.08, P < 0.05).ConclusionsBased on the results of this investigation, we established a link between monocyte count and the severity of HAdV pneumonia. Monocyte count is negatively associated with severe HAdV pneumonia. The inflection point of monocyte count detected in the two-stage linear regression model was 1.5 × 109/L.

1356. Case Series of Children with Hepatitis and Adenovirus Infection, Alabama, October 2021—February 2022

Abstract Background Human adenoviruses (HAdV) are a common cause of respiratory and gastrointestinal infections but rarely cause end-organ disease in children. From October 2021 to February 2022, several previously healthy children admitted to a single center for significant hepatitis also tested positive for HAdV. The aim of this investigation is to describe characteristics of these children. Methods Children admitted to Children’s of Alabama (COA) from October 2021 to February 2022 with hepatitis who tested positive for HAdV by whole blood RT-PCR were included. Demographic, clinical, laboratory and treatment data were collected from medical records. Residual blood specimens were sent for adenovirus typing. Results Nine pediatric patients with hepatitis and HAdV infection were identified (78% female; median age 3.0 years; IQR 1.7-3.0). Before admission, six reported diarrhea and three had respiratory symptoms. At presentation, eight had scleral icterus, six had jaundice, seven had hepatomegaly, and one was encephalopathic. All patients had elevated transaminases (AST range: 447-4000 U/L, ALT range: 784-4695 U/L); initial total bilirubin varied [range 0.23-13.5 mg/dL]). All had confirmed HAdV by RT-PCR on whole blood (initial qPCR range: 991-70,680 copies/mL). Notably, two children who transferred to another facility were negative for HAdV by RT-PCR when plasma was tested (instead of whole blood). Six children underwent liver biopsy showing varying degrees of hepatitis with no adenovirus detected on immunohistochemistry stains. Five children had HAdV type 41 confirmed. Three children presented or progressed to acute liver failure, two children were treated with cidofovir, and two underwent successful liver transplantation. No known epidemiologic links between patients were identified and all were from geographically distinct parts of Alabama. Conclusion HAdV is a potentially underrecognized cause of hepatitis. Whole blood specimens may be preferred over plasma for HAdV RT-PCR testing. HAdV type 41 was identified in all patients with typing results available. Improved type-based surveillance may help determine HAdV patterns of circulation and inform future diagnostic testing. Disclosures William Britt, MD, First Energy Corporation: Stocks/Bonds|Hookipa Pharma: Advisor/Consultant|Kroger Care: Stocks/Bonds|MDU Resources Group: Stocks/Bonds|PG&amp;E Corporation: Stocks/Bonds.

Molecular typing and epidemiology profiles of human adenovirus infection among children with severe acute respiratory infection in Huzhou, China.

Human adenoviruses (HAdVs) are prevalent worldwide and are a common cause of respiratory tract infection in people of all ages. However, little is known about HAdV infection among children with severe acute respiratory infection (SARI). The present study retrospectively analysed the molecular typing and epidemiological characteristics of HAdV-positive samples from children with SARI from January 2017 to December 2021 in Huzhou. The results showed that 89 (8·27%) of 1078 SARI paediatric patients were positive for HAdVs. Children <5 years of age accounted for 87·64% of the positive cases. The peak seasons for HAdV infection were the first quarter and the fourth quarter. In addition, HAdV-B and HAdV-C were circulating among paediatric patients with SARI, of which the B3 genotype (n = 30, 51·72%) was the most prevalent and was detected every year, indicating that B3 is the main epidemic strain in the Huzhou area, followed by C1 (n = 9, 15·52%), C2 (n = 7, 12·07%) and B7 (n = 5, 8·62%). These findings provide a benchmark for future epidemiology and prevention strategies for HAdVs.

Molecular epidemiology of human adenoviruses in children with and without respiratory symptoms: Preliminary findings from a case-control study

BackgroundHuman adenovirus (HAdV) is an important viral agent in children which can lead to severe acute respiratory infection (SARI). Reports on molecular epidemiology of HAdVs in Iran are limited. This case-control study is conducted to compare the HAdV infection rate and molecular epidemiology among two groups of children with and without respiratory symptoms in Tehran, Iran during 2018–2019.MethodsNested PCR was performed on 120 oropharyngeal swabs taken from children aged five and younger with SARI who were hospitalized as the case group, and 120 oropharyngeal swabs were collected from children of the same age without respiratory symptoms as the control group. For positive samples Sanger sequencing was done and a phylogenetic tree was drawn afterward.ResultsOut of 120 cases, 8 (6.6%) tested positive for eachHAdV types including 6 (75%) HAdV-B7, 1 (12.5%) HAdV-C2, and 1 (12.5%) HAdV-C6. Among the control group, out of 120 samples, 8 (6.6%) were positive comprising 5 (62.5%) HAdV-C5, 2 (25%) HAdV-F41, and 1 (12.5%) HAdV-C6.ConclusionThe present study indicated a different viewpoint of HAdV molecular epidemiology in which the genotypes were compared in children with and without respiratory symptoms. HAdV prevalence was equally common in cases and controls but different genotypes were detected in these two groups. HAdV-B7 was the main type among children with SARI, dissimilar to children with no respiratory symptoms where HAdV-C5 was the predominant type. Detecting HAdV-F in oropharyngeal swabs was a rare finding, which requires further investigation.

PML Alternative Splice Products Differentially Regulate HAdV Productive Infection.

ABSTRACTPromyelocytic leukemia nuclear bodies (PML-NBs) were considered to maintain antiviral capacity, as these spherical complexes are antagonized by viruses. Actual work provides evidence, that PML-NB-associated factors might also be beneficial for distinct viral processes indicating why genomes and replication centers of nuclear replicating viruses are often found juxtaposed to PML-NBs. Several early HAdV proteins target PML-NBs, such as E4orf3 that promotes redistribution into track-like structures. PML-associated dependency factors that enhance viral gene expression, such as Sp100A remain in the nuclear tracks while restrictive factors, such as Daxx, are inhibited by either proteasomal degradation or relocalization to repress antiviral functions. Here, we did a comprehensive analysis of nuclear PML isoforms during HAdV infection. Our results show cell line specific differences as PML isoforms differentially regulate productive HAdV replication and progeny production. Here, we identified PML-II as a dependency factor that supports viral progeny production, while PML-III and PML-IV suppress viral replication. In contrast, we identified PML-I as a positive regulator and PML-V as a restrictive factor during HAdV infection. Solely PML-VI was shown to repress adenoviral progeny production in both model systems. We showed for the first time, that HAdV can reorganize PML-NBs that contain PML isoforms other then PML-II. Intriguingly, HAdV was not able to fully disrupt PML-NBs composed out of the PML isoforms that inhibit viral replication, while PML-NBs composed out of PML isoforms with beneficial influence on the virus formed tracks in all examined cells. In sum, our findings clearly illustrate the crucial role of PML-track formation in efficient viral replication.IMPORTANCE Actual work provides evidence that PML-NB-associated factors might also be beneficial for distinct viral processes indicating why genomes and replication centers of nuclear replicating viruses are often found juxtaposed to PML-NBs. Alternatively spliced PML isoforms I-VII are expressed from one single pml gene containing nine exons and their transcription is tightly controlled and stimulated by interferons and p53. Several early HAdV proteins target PML-NBs, such as E4orf3, promoting redistribution into track-like structures. Our comprehensive studies indicate a diverging role of PML isoforms throughout the course of productive HAdV infection in either stably transformed human lung (H1299) or liver (HepG2) cells, in which we observed a multivalent regulation of HAdV by all six PML isoforms. PML-I and PML-II support HAdV-mediated track formation and efficient formation of viral replication centers, thus promoting HAdV productive infection. Simultaneously, PML-III, -IV,-V, and -VI antagonize viral gene expression and particle production.

Molecular and epidemiological characterization of human adenoviruses infection among children with acute diarrhea in Shandong Province, China

BackgroundHuman adenovirus (HAdV) had been recognized as one of the most common enteric viruses associated with acute diarrhea in children. The present study was carried out to demonstrate the molecular and epidemiological characterization of HAdV Infections among children in Shandong province in China between July 2017 and June 2018.MethodsFecal specimens were collected from children under 5 years old with acute diarrhea. DNA was extracted from the stool specimens and adenovirus DNA was detected by PCR amplification with specific primers. The amplification products were subjected to electrophoresis and visualized on a UV transilluminator. All positive RT-PCR amplification products were sequenced and the obtained sequences analyzed by MEGA (version 7.0). Demographic information and clinical manifestation data were also analyzed.ResultsIn total, 656 fecal specimens were collected and the overall positive rate of HAdV was 7.47%. HAdV infections were detected in all age groups, in which children aged 13–24 months presented the highest positive rate. Seasonal pattern could be observed with a peak in December, January and February. Diarrhea, vomiting, dehydration and fever were the main clinical manifestations, in which vomiting was the most common accompanied symptom. By phylogenetic analysis, four species (A, B, C, and F) were detected and seven different serotypes were identified. HAdV-41 (48.98%, 24/49) was the most common serotype followed by HAdV-3 (18.37%, 9/49), HAdV-31 (14.29%, 7/49), HAdV-7 (8.16%, 4/49), HAdV-40 (4.08%, 2/49), HAdV-1 (4.08%, 2/49) and HAdV-2 (2.04%, 1/49).ConclusionThis study indicated that HAdV infection was an important cause of acute diarrhea among children under 5 years old in Shandong province. The results will contribute to (a) increase understanding of the role of HAdV in diarrheal children and enhance identification of the predominant diarrhea pathogen for diagnosis; (b) avoid abuse of antibiotics; (c) monitor the change of prevalent HAdV serotypes and promote vaccine development and vaccination.

Genetic characterization and phylogenetic variations of human adenovirus-F strains circulating in eastern India during 2017-2020.

Human adenovirus-F (HAdV-F) (genotype 40/41) is the second-most leading cause of pediatric gastroenteritis after rotavirus, worldwide, accounting for 2.8%-11.8% of infantile diarrheal cases. Earlier studies across eastern India revealed a shift in the predominance of genotypes from HAdV41 in 2007-09 to HAdV40 in 2013-14. Thus, the surveillance for HAdV-F genotypes in this geographical setting was undertaken over2017-2020 to analyze the viral evolutionary dynamics. A total of 3882 stool samples collected from children (≤5 years) were screened for HAdV-F positivity by conventional PCR. The hypervariable regions of the hexon and the partial shaft region of long fiber genes were amplified, sequenced, and phylogenetically analyzed with respect to the prototype strains. A marginal decrease in enteric HAdV prevalence was observed (9.04%, n = 351/3882) compared to the previous report (11.8%) in this endemic setting. Children <2 years were found most vulnerable to enteric HAdV infection. Reduction in adenovirus-rotavirus co-infection was evident compared to the sole adenovirus infection. HAdV-F genotypes 40 and 41 were found to co-circulate, but HAdV41 was predominant. HAdV40 strains were genetically conserved, whereas HAdV41 strains accumulated new mutations. On the basis of a different set of mutations in their genome, HAdV41 strains segregated into 2 genome type clusters (GTCs). Circulating HAdV41 strains clustered with GTC1 of the fiber gene, for the first time during this study period. This study will provide much-needed baseline data on the emergence and circulation of HAdV40/41 strains for future vaccine development.

Alterations in biochemical markers in adenovirus infection.

BackgroundAnalyze possible relationships between HAdV and markers for inflammation, specifically the C-reactive protein (CRP) and procalcitonin (PCT) tests, along with other haematological markers.MethodsRetrospective study of 487 children presenting with fever and/or acute respiratory symptoms in the Paediatric Emergency Department. Analyses included viral presence/absence (both HAdV and other respiratory viruses) in respiratory exudates, CRP and PCT alterations in plasma, and haematological markers in whole blood.ResultsViral load was >500 copies/103 cells of HAdV in 127 cases (26.1%), of which 66 (52%, P<0.0001) had alterations in PCT, and 112 (88.1%, P<0.0001) in CRP. Haematological markers were similar either HAdV was present or not, although many HAdV positive patients demonstrated leukocytosis (66%). Bacterial cultures from 141 samples showed altered PCT in 27 (60%) with HAdV infection, in 3 (18.7%) with bacterial infection, and 13 (26.5%) without either viral or bacterial infection (P<0.05). CRP was altered in 88.9% of HAdV infected children and in 87% infected with bacteria, although the percentage was greater than in cases where other respiratory viruses were present (61.3% P<0.05).ConclusionsResults demonstrate a clear relationship between HAdV infection and alterations in PCT and CRP which should be taken into account in paediatric patient management.

#18: Brincidofovir for the Treatment of Disseminated Human Adenovirus Infection in Pediatric Solid-organ Transplant Recipients

Abstract Background Human adenovirus (HAdV) viremia can cause significant morbidity among pediatric patients undergoing solid-organ transplantation (SOT). Currently, there are no US Food and Drug Administration (FDA)-approved treatments for HAdV infections, and historically the mainstay of treatment has been decreasing immunosuppression with antiviral therapies reserved for those with severe disease. Brincidofovir (BCV) is an investigational antiviral drug with potency against HAdV. We describe four cases of disseminated HAdV infection treated with (BCV) among pediatric SOT patients. Methods We retrospectively reviewed 4 cases of severe disseminated HAdV infection, which occurred between 2018 and 2019, in a tertiary pediatric transplant center. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. Baseline clinical characteristics, disease course, treatment, and outcomes were reviewed. Results Four pediatric SOT patients (2 kidneys, 1 dual kidney/liver, and 1 liver) ranging in age from 9 months to 19 years were diagnosed with HAdV infection (Table 1). Patients presented with varied symptoms from 12 to 912 days post-transplant. Peak HAdV viral load ranged from 37,000 to &amp;gt;1,000,000 copies/mL. All patients had disseminated disease with evidence of graft involvement and varying degrees of acute kidney injury (AKI) making them candidates for BCV therapy over cidofovir to avoid nephrotoxicity. Three out of four patients received cidofovir prior to conversion to BCV. IRB-approved compassionate use of BCV was dosed at 2 mg/kg (max 100 mg) twice weekly PO along with reduced immunosuppression. Resolution of symptoms and HAdV viremia was seen at a mean of 21.5 days (range 15–32) of therapy. All patients had resolution of AKI with a return to baseline creatinine after therapy. Conclusions Though HAdV infection in pediatric SOT patients is uncommon, a subset of patients experience severe disease, morbidity, and graft loss. Currently, HAdV is not routinely monitored in pediatric SOT transplant patients. Although supportive care and decreased immunosuppression remain as the most important component of therapy, BCV was well tolerated and efficacious in our series. Further research is needed to better understand risk factors for HAdV infection and potential antiviral treatment options to improve patient outcomes.

Adenovirus infection in children hospitalized with pneumonia in Guangzhou, China.

BackgroundHAdV infection can cause a variety of diseases. Although infections with HAdVs often are mild, life‐threatening respiratory disease can occur. Pneumonia is one of the more serious types of HAdV‐induced respiratory disease in children. In this study, we determined the prevalence and genotype of HAdVs among children hospitalized with pneumonia in Guangzhou, China.MethodsNasopharyngeal swabs (NPSs) were collected from children hospitalized with pneumonia in Guangzhou, China, from January 2013 to June 2019. HAdVs were detected by real‐time polymerase chain reaction assay, and hexon, fiber, and penton gene were amplified and used for phylogenetic analysis. Epidemiological data were analyzed using SPSS16.0 software.Results and ConclusionsA total of 1778 children hospitalized with pneumonia were enrolled. The overall HAdV detection rate was 3.26%. And the yearly detection rate varied from around 2.5% in 2013‐2017 to around 6% in 2018‐2019. Children >5 years had the highest HAdV infection rate. 92.86% of HAdV sequences obtained in this study were belonged to species B, and no recombination was observed. HAdV‐B7 and HAdV‐B3 were the common types detected in the study period, with the predominant HAdV genotype shifted from HAdV‐B3 in 2015‐2016 to HAdV‐B7 in 2017‐2018. The discrepancies in HAdV detection rates in different study period and changes of HAdV predominant types over time highlighted the importance of continued surveillance.

Outbreaks of Adenovirus-associated Respiratory Illness on 5 College Campuses in the United States, 2018-2019.

Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, 5 United States (US) colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. A case was defined as a student at one of the 5 colleges, with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018-December 2018 or March-May 2019. Available respiratory specimens were typed by HAdV type-specific real-time polymerase chain reaction assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. We identified 168 HAdV cases. Median age was 19 (range, 17-22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; 2 cases died. Among questionnaire respondents, 80% (75/94) missed ≥ 1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on 5 US college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses.

Structure-Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection.

The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (11, 13, 14, 17, 20, 58, 60, 62, and 70) showed significantly improved anti-HAdV activities with nanomolar to submicromolar IC50 values and high selectivity indexes (SI > 100), indicating better safety windows, compared to those of the lead compound niclosamide. Our mechanistic assays suggest that compounds 13, 62, and 70 exert their activities in the HAdV entry pathway, while compounds 14 and 60 likely target the HAdV DNA replication, and 11, 17, 20, and 58 inhibit later steps after DNA replication. Given the broad anti-viral activity profile of niclosamide, these derivatives may also offer therapeutic potential for other viral infections.

Transfer of Hexon‐ and Penton‐selected adenovirus‐specific T cells for refractory adenovirus infection after haploidentical stem cell transplantation

Adenovirus (HAdV) infections confer a high risk of morbidity and mortality for immunocompromised patients after stem cell transplantation (SCT). Treatment with standard antiviral drugs is of limited efficacy and associated with a high rate of adverse effects. HAdV-specific T cells are crucial for sustained viral elimination and the efficacy of adoptive T-cell therapy with donor-derived HAdV-specific T cells has been reported by several investigators. Here, we report our experience with the transfer of HAdV-specific T cells specific for penton, which was recently identified as an immunodominant target of T cells, and hexon in a 14-year-old boy after T-cell-depleted haploidentical SCT for myelodysplastic syndrome (MDS). He developed severe HAdV-associated enteritis complicated by acute graft-versus-host disease (GvHD). The patient received ten infusions of allogeneic HAdV-specific T cells manufactured from the haploidentical stem cell donor using the CliniMacs Interferon-γ (IFN-γ) cytokine capture and immunomagnetic selection. Initially, T cells were generated against the immunodominant target hexon and in subsequent transfers dual antigen-specific T cells against hexon and penton were applied. T-cell transfers were scheduled individually tailored to current immunosuppressive treatment. Each transfer was followed by reduction of HAdV load in peripheral blood and clinical improvement. Importantly, T-cell responses to both penton and hexon pools emerged in patient blood after repetitive transfers. Unfortunately, the patient experienced bacterial sepsis, and in this context, severe GvHD requiring intensive immunosuppression followed by secondary progression of HAdV infection. The patient succumbed to multiorgan failure 283days after SCT. This case demonstrates the feasibility of HAdV-specific T-cell transfer even in the presence of immunosuppressive treatment. Targeting of multiple immunodominant viral proteins may prove valuable in patients with complicated HAdV infections.