Adenovirus Infection Research Articles

The Outcomes of Adenovirus Infection in Kidney Transplant Recipients.

Adenovirus (ADV) infection can lead to significant morbidity and mortality in immunocompromised patients, particularly in those with hematopoietic stem cells or solid organ transplants. The incidence of ADV infection in kidney transplant (KT) is not well-defined as ADV is often asymptomatic and not routinely checked. This retrospective case-series study included KT and simultaneous pancreas-KT (SPKT) recipients from January 1, 2008, to January 31, 2024, across three Mayo Clinic sites (Arizona, Florida, and Minnesota) with symptomatic adenovirus polymerase chain reaction cases. The primary outcomes were allograft function at various intervals post-ADV infection, allograft, and patient survival. We report one of the largest multi-site case series regarding outcomes of ADV in KT with 17 patients. The median time to ADV infection was 30 weeks (5-74). Five patients (29%) developed disseminated infection. Nine patients (53%) of the entire cohort experienced graft loss within a median of 35 (4-168) weeks, with four (44%) of graft loss attributed to ADV. Nine patients (53%) developed rejections post-ADV infection with a median of 4 (2-8) weeks after resolution. One patient died from acute hypoxic respiratory failure from ADV infection. ADV should be considered in KT/SPKT patients with renal dysfunction, hematuria, and with or without fever. Despite the low mortality rate, there is a significant risk of graft loss and rejection after ADV infection. It is crucial to screen for ADV and develop intervention strategies for treatment. Further multicenter studies are needed to better define, stage, and manage ADV infection.

Results of monitoring probable cases of acute severe hepatitis of unknown etiology in children in Мoscow in 2022

In the spring 2022, the number of cases of severe acute hepatitis of unknown etiology was unusual increased in Europe. As an immediate response, the World health organization recommended active efforts to identify such cases at the international level. For monitoring of acute hepatitis in Moscow, patients with suspected liver disease were sent to Infectious Diseases Clinical Hospital No. 1. The goal: study of the structure of diseases occurring with liver damage in children hospitalized in 2022. Materials and methods: analysis of medical records of children hospitalized with a diagnosis of hepatitis from May 1 to December 31, 2022. Еpidemiological data (age, gender, parenteral manipulations, contacts with patients, travel abroad), clinical (fever, jaundice, etc.), laboratory parameters were assessed. Results: A total of 164 completed cases of hepatitis in children aged 5 months to 17 years were analyzed. 36 children met the criteria for probable severe acute hepatitis of unknown etiology. Age median was 7 years [2.25;11]. Girls made up more than half (21 (58.3%). Non-infectious genesis was established in 15 (41.6%). The infectious disease was verified in 11 (30.5%), of which adenoviral infection was detected in 2 children. In 9 (25%) children the etiology of hepatitis was not established. Conclusion. Various infectious and non-infectious diseases among hospitalized children lead to a significant increase in liver transaminases. Most acute hepatitis with unspecified etiology proceeded as an acute infectious disease and ended in recovery. The role of adenoviruses in the development of severe hepatitis in children was not confirmed in our study.

Comparative analysis of the epidemiological characteristics of adenovirus, rotavirus A, and coinfection in children during 2014-2023 in Guangzhou, China.

Infection is the cause of diarrhoea, and rotaviruses and adenoviruses are important pathogens in children. A retrospective study was conducted on 144,067 children with diarrhoea between 2014 and 2023 in China. We used the colloidal gold method to detect intestinal adenovirus and rotavirus A antigens in faeces. The epidemiological characteristics of these viruses and the impact of meteorological factors on them were analysed before and after coronavirus disease 2019 (COVID-19) pandemic. During this decade, the positive rate of adenovirus infection was 6.41%, while the positive rate of rotavirus A infection was 11.81%, higher than that of adenovirus infection. The positive rate of adenovirus and rotavirus A coinfection was 1.92%. The positive rates of adenovirus, rotavirus A and coinfection showed a fluctuating trend, and suddenly decreased in 2020. There was an apparent decrease of positive rate of rotavirus A, with a decrease of 57.27%, during 2020-2023. Surprisingly, the positive rate of adenovirus infection exceeded that of rotavirus A infection in 2021 and 2023. During the COVID-19 pandemic, the proportion of female patients and children over two years of age infected with adenovirus or rotavirus A increased, while the proportion of cases in winter decreased. In addition, we found that the positive rate of rotavirus A infection was related to average temperature and sunshine, and the positive rate of adenovirus and rotavirus A coinfection was only related to sunshine. However, these correlations disappeared during the COVID-19 pandemic. This study revealed the recent prevalence of adenovirus and rotavirus A infections in children with diarrhoea in south-central China and provided a theoretical basis for the prevention and control of viral diarrhoea.

Diels–Alder Adducts of <i>N</i>-Substituted 2-Pyridones with Maleinimides. Synthesis and Antiviral Activity

Adducts of N-substituted 2-pyridones [pyridine-2(1H)-ones] and N-substituted maleic acid imides were synthesized under thermal conditions of the Diels–Alder reaction with yields from 68 to 97%. Cytotoxicity and antiviral activity of the obtained compounds were studied using a model of adenovirus infection [human adenovirus type 5 (AdV5)] in MA-104 cell culture. It was shown that the synthesized adducts have low toxicity and medium antiviral activity. Only 9-hexyl-2-phenyl-3a,4,7,7a-tetrahydro-1H-4,7-(epiminomethano)isoindole-1,3,8-trione has the most pronounced viral inhibitory properties with a selectivity index of 7.

Abstract 4121816: Viral Venture: A Case of Myocarditis and IgA Vasculitis from Adenovirus Infection

Case Description: A 19-year-old man presented to the emergency department for 3 days of shortness of breath, progressive bilateral lower extremity rash, generalized fatigue, and diffuse joint following an earlier visit to urgent care for pharyngitis symptoms. Physical exam was notable for tachycardia, pain with active wrist and ankle range of motion, pharyngeal erythema, cervical adenopathy, and confluent erythematous palpable purpura and petechiae noted on bilateral lower extremities with scattered lesions on his thighs, arms, and back. Laboratory workup notable for markedly elevated high-sensitivity troponin to 3398 ng/L, and elevated CRP. Further workup was notable for normal urinalysis, negative streptococcus antigen, negative ANCA antibodies, ANA, Hepatitis B and C, and cryoglobulins. Imaging and cardiac workup were notable for normal left ventricular function and cardiac MRI notable for late gadolinium enhancement in the anteroapical mid-myocardial region suggestive of myocarditis. Skin biopsy ultimately revealed immunodeposition of IgA on superficial capillaries compatible with a diagnosis of IgA vasculitis. The patient was started on steroids for IgA vasculitis with rapid improvement in his symptoms and he was discharged home in good condition. Discussion: Recognizing the severe complications of viral infection can lead to prompt treatment and prevention of progression to severe end organ damage. Our case highlights rarely reported cardiac involvement of IgA vasculitis secondary to adenovirus infection based on laboratory and imaging diagnosis with cardiac MRI. To date, only 16 cases of cardiac involvement in IgA vasculitis have been reported. This case adds to the limited body of published cases describing this presentation of IgA vasculitis and is also consistent with the results of prior cases suggesting that an immunosuppressive regimen including glucocorticoids may help to prevent disease progression and induce remission in cases with cardiac involvement without the need for endomyocardial biopsy.

EXTH-34. ACETYLATION SUPPRESSION MEETS ONCOLYTIC VIRUSES FOR THE TREATMENT OF PEDIATRIC DIFFUSE MIDLINE GLIOMA

Abstract Diffuse midline glioma (DMG) remains a devastating pediatric brain tumor without effective treatment. In a recent clinical trial, we demonstrated the feasibility and efficacy of Delta-24-RGD oncolytic virus combined with radiation therapy in patients with newly diagnosed diffuse intrinsic pontine gliomas (NCT03178032). Because the adenoviral protein E1A binds to P300 and redirects acetylation upon virus infection, we hypothesized that combining oncolytic adenoviruses with P300 inhibitors will cause a remarkable shifting in acetylation and the post-translational landscape of DMG, ultimately enhancing the anti-glioma effect of oncolytic viruses. Western blot analyses showed a longitudinal reduction in H3K27ac (89%) and H3K18ac (99%) in a panel of human (TP54 and SF8628) and murine (24B_1 and 26C_7) DMG cells after Delta-24-RGD infection. In addition, using histone fractionation by high-performance liquid chromatography, we detected an increase in total H3 upon adenovirus infection. Mass spectrometry of histones in the human DIPG cell line, TP54 using middle-down approach illustrated post-translational changes across histones, including hypoacetylation of the H3.2K14 mark. To further modify histone acetylation in DMG during Delta-24-RGD infection, we combined virotherapy with C646, a selective and competitive histone acetyltransferase inhibitor of the E1A-binding p300/CBP complex of proteins. In vitro, the combination of Delta-24-RGD with C646 synergistically increased cell death in a panel of human and murine DIPG cell lines (zip-scores ranging from 6.3-11.3 with zip-scores above 10 being indicative of synergy). Ongoing experiments using a panel of adenoviruses expressing E1A with defective P300 binding or expressing a dominant-negative form of P300 or wild-type P300 are designed to test the extent to which E1A binding of P300 drives hypoacetylation in DMG upon virus infection. In addition, we are performing in vivo experiments to establish the anti-cancer effect of the combination of Delta-24-RGD and P300 inhibitors in clinically relevant animal models of DMG, with a feasible translation to the clinic.

IMMU-11. GUARDIANS OF INNATE IMMUNE ACTIVATION: CRUCIAL ROLES OF NONO AND CGAMP IN GLIOMA VIROTHERAPY

Abstract Despite aggressive therapeutic interventions, glioblastoma patients face a median survival of seven months after tumor recurrence. Alarmingly, there has been no improvement to the standard of care for two decades, and patients still receive toxic doses of radiation and chemotherapy, rendering many unable to perform daily functions. An emerging approach, oncolytic virotherapy (OV) using Delta-24-RGD, is gaining traction due to recent clinical trials (NCT00805376, NCT03178032, and NCT02798406) exhibiting robust responses in subsets of patients. While these studies demonstrated the therapeutic potential of OV, findings also indicate the early clearance of the virus, hindering the establishment of an effective anti-tumor immune response in most patients. We propose that mitigating the innate immune response against the therapeutic virus should result in improved intratumoral persistence, increasing the window of opportunity for developing an anti-tumor immune response. RNA-sequencing identified the non-POU domain containing octamer-binding (NONO) pathway as highly upregulated in syngenic glioma models and further amplified by OV treatment. In-vitro RNA sequencing and comparative analysis complemented these results to define a unique transcriptomic profile induced by adenovirus infection. LC-MS/MS identified host cGAS and adenoviral capsid proteins as candidate binding partners of NONO, which were validated using co-immunoprecipitation. Although the type I interferon cluster is deleted in most gliomas, tumor cells have a profound influence on their microenvironment through the secretion of the second messenger cGAMP. We show that NONO is required for cGAMP production, providing a mechanism to modulate antiviral responses in the tumor microenvironment during OV. Our findings underscore the significance of cGAMP shed from tumor cells in response to OV, and how NONO interacts with cGAS in the nucleus to sensor adenovirus infection. These findings uncover novel innate immunity mechanisms in gliomas and will inform the design of more efficacious oncolytic adenoviruses for glioma therapy.

Construction and validation of a mouse model for studying severe human adenovirus infections

Human adenoviruses (HAdVs) are highly contagious pathogens with various genotypes implicated in acute respiratory disease (ARD) and linked to mortality, especially in immunosuppressed patients, young children, and military recruits. Currently, no vaccines or specific drugs are approved for clinical use. The hosts of adenoviruses are strictly species-specific, which strongly limits the development of vaccines and drugs against HAdVs. In this study, immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5 (HAdV-5) via tail intravenous injection (i.v.). All mice challenged with a high dose of HAdV-5 (3.2×1010 TCID50/kg) died within 3 to 5 days, while those receiving a low dose of HAdV-5 (8×109 or 4×109 TCID50/kg) survived. Interestingly, among the mice receiving a medium dose of HAdV-5 (1.6×1010 TCID50/kg), 60% (n = 3/5) of male mice died, while all female mice survived. This suggests that male mice may be more susceptible to HAdV-5 infection than female mice, consistent with clinical findings in children. HAdV-5 DNA was mainly distributed in the liver, followed by the spleen and lungs. Pathological changes were observed in the lungs, liver, and spleen, with severity increasing in correlation with the virus challenge dosage. Transcriptome and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa, H2-Ea-ps, CD74, and H2-Eb1 genes in male mice, as well as the AHR gene in female mice, may contribute to the observed higher mortality rates in male mice. Therefore, this effective, feasible, and cost-efficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.

Uncovering the Potent Antiviral Activity of the Sesterterpenoids from the Sponge Ircinia Felix Against Human Adenoviruses: from the Natural Source to the Total Synthesis.

Human Adenovirus (HAdV) infections in immunocompromised patients can result in disseminated diseases with high morbidity and mortality rates due to the absence of available treatments for these infections. The sponge Ircinia felix was selected for the significant anti-HAdV activity displayed by its organic extracts. Its chemical analysis yielded three novel sesterterpene lactams, ircinialactams J-L, along with three known sesterterpene furans which structures were established by a deep spectrometric analysis. Ircinialactam J displayed significant antiviral activity against HAdV without significant cytotoxicity, showing an effectiveness 11 times greater than that of the standard treatment, cidofovir®. Comparison of the antiviral evaluation results of the isolated compounds allowed us to deduce some structure-activity relationships. Mechanistic assays suggest that ircinialactam J targets an early step of the HAdV replicative cycle before HAdV genome reaches the nucleus of the host cell. The first total synthesis of ircinialactam J was also accomplished to prove the structure and to provide access to analogues. Key steps are a regio- and stereoselective construction of the trisubstituted Z-olefin at Δ7 by iron-catalyzed carbometallation of a homopropargylic alcohol, a stereoselective methylation to generate the stereogenic center at C18, and the formation of the (Z)-Δ20 by stereoselective aldol condensation to introduce the tetronic acid unit. Ircinialactam J is a promising chemical lead to new potent antiviral drugs against HAdV infections.

Bacterial-like inflammatory response in children with adenovirus leads to inappropriate antibiotic use: a multicenter cohort study.

To compare the clinical severity of Human Adenovirus (HAdV) infection with other viral diseases in a cohort of children, evaluating presentation, therapy, and outcome. We conducted a retrospective multicenter cohort study in Italian children hospitalized from January to December 2023 for respiratory symptoms. The study included children with HAdV infection presenting primarily with respiratory symptoms. Patients with isolated gastrointestinal involvement or coinfection with bacteria were excluded. A total of 171 children were enrolled: 98 with HAdV infection (age 44.3 ± 37.9 months) and 73 with other viruses (age 20.4 ± 27.2 months). In the first group, 57.1% had a coinfection with one or more additional viruses. The most common symptoms were fever (89.8%), cough (73.5%) and sore throat (52%). Respiratory distress and hypoxemia were more frequent in the non-HAdV group. Children with HAdV infection demonstrated significantly higher C-reactive protein levels (50.8 ± 54.2 vs. 16.5 ± 33.8mg/L, p < 0.001), experienced a longer duration of fever (4.9 ± 3.6 vs. 3.4 ± 2.3 days, p = 0.009) and were more likely to receive antibiotic treatment (77.6% vs. 27.4%, p < 0.001). No differences were observed in hospitalization stay, rate of complications, and ICU admission. Interestingly, our data suggests that HAdV-infected children exhibit a more pronounced inflammatory response despite experiencing less severe respiratory symptoms compared to other viruses. The presence of prolonged fever and a strong inflammatory response often leads to antibiotic overuse during the initial phase, when the viral etiology is yet to be confirmed. Early and accurate identification of HAdV infection is crucial to optimize treatment strategies and minimize unnecessary antibiotic use.

Adenoviral fiber-knob based vaccination elicits efficient neutralizing antibodies and T cell responses against adenovirus infection

BackgroundHuman adenoviruses (HAdVs) frequently cause common respiratory or gastrointestinal infections among children, adults, individuals with immune deficiencies, and other vulnerable populations with varying degree of symptoms, ranging from mild to server, and in some cases, even fatalities. Despite the significant clinical impact of HAdVs, there is currently no approved vaccine available.MethodsThis study explores the potential of the adenovirus type 5 fiber knob (Ad5-FK) to stimulate the production of Ad-specific neutralizing antibodies and T-cell responses in mice. Based on structure predictions, we first expressed Ad5-FK in E. coli and confirmed the assembly of FK into its trimeric form. After testing the binding capability of the trimeric FK to susceptible cells, the immunogenicity of the protein in combination with the c-di-AMP adjuvant was assessed in BALB/c mice.ResultsThe purified Ad5-FK exhibited self-trimerization and maintained correct conformation akin to the authentic FK structure. This facilitated effective binding to susceptible HEK293 cells. Notably, the protein demonstrated significant inhibition of HEK293 cells infection by rAd5-GFP. Immunization of BALB/c mice with Ad5-FK, or Ad5-FK mixed with c-di-AMP yielded FK-specific antibodies with potent neutralization capacity. Significantly, Ad5-FK was found to elicit a vigorous CD4+ T-cell response in the immunized mice.ConclusionOur findings underscore the efficacy of FK-based vaccine in eliciting anti-Ad humoral immune response and CD4 T-cell immune reactions essential for protection against viral infections.

Epidemiology and clinical characteristics of acute viral gastroenteritis in 350 paediatric patients hospitalised between 2019 and 2022 in the Military Institute of Medicine – National Research Institute in Warsaw, Poland: a single-centre retrospective analysis

Introduction and objective: Acute gastroenteritis, a common childhood illness worldwide, manifests with symptoms including fever, abdominal pain, vomiting, and diarrhoea. It is highly contagious, with transmission occurring through contaminated water, food, or poor hygiene. Globally, 1.7 billion cases of diarrhoeal diseases are diagnosed annually, causing approximately 525,000 deaths among children under the age of five. Dehydration caused by diarrhoea is a primary cause of hospitalisation, particularly in developing countries. Aim: Analysis of the aetiology, frequency, and seasonal distribution of viral pathogens responsible for acute gastroenteritis in children hospitalised between 2019 and 2022 at the Military Institute of Medicine – National Research Institute in Warsaw, Poland. Materials and methods: Medical records of patients aged 0 to 18 diagnosed with rotavirus, norovirus, and adenovirus-induced acute gastroenteritis were analysed. The pathogens had been identified with reliable immunochromatographic tests. Exclusion criteria encompassed bacterial infections, dietary errors, and inflammatory conditions. Data examined included age, gender, aetiology of gastroenteritis, seasonality, duration of hospitalisation, and clinical symptoms (diarrhoea, vomiting, fever, abdominal pain, and dehydration). Laboratory results such as white blood cell count, C-reactive protein, electrolyte levels, and organ function markers were also evaluated. Results: Data from 350 children hospitalised between 2019 and 2022 were analysed. The highest number of hospitalisations occurred in 2019 and 2022, with fewer cases in 2020–2021, likely reflecting the impact of the COVID-19 pandemic. Most patients were between 6 and 12 months old. Rotavirus infection commonly presented with fever, vomiting, diarrhoea, and dehydration. Adenovirus and mixed infections were associated with slightly higher C-reactive protein levels, while rotavirus infections showed mildly elevated aspartate aminotransferase levels. Haematocrit, blood urea nitrogen, creatinine, and electrolyte levels were similar across all cases. Conclusions: Our analysis showed that rotavirus was the most frequent cause of acute viral diarrhoea in children, followed by norovirus and adenovirus, with mixed infections being the least common. The peak incidence occurred in autumn and winter, except in 2021, reflecting changes in the dynamics of infections related to the coronavirus pandemic. Biochemical findings were not sufficiently characteristic to infer the aetiology of the disease.

Severe Clinical Outcomes Due to Human Adenoviral Respiratory Infections in Hospitalized Immunocompetent Adults

Background Human adenoviral infections typically result in upper respiratory tract infections, conjunctivitis, and gastroenteritis that is classically self-limiting but can be life-threatening in immunocompromised individuals. In relatively rare cases, adenovirus infections in immunocompetent patients can result in hospitalizations and severe outcomes that include need for critical care or death. The risk factors that are associated with severe adenoviral infections in immunocompetent hosts have not been thoroughly investigated and are currently poorly understood. Methods Retrospective cohort of 78 patients with ages ranging from 18–85 years who were admitted to Yale New Haven-affiliated hospitals over a period of 2 years with positive adenovirus tests on a nasopharyngeal respiratory viral panel. Immunocompromised patients were excluded from the study. Patient charts were reviewed to obtain demographic information, comorbid conditions, smoking history, and clinical outcomes. Results Of the 78 patients admitted, 15 (19.2%) were admitted as observation, 44 (56.4%) were admitted to the hospital for over 48 hours, 15 (19.2%) required critical care, and 4 (5.1%) expired during hospitalization. Pulmonary disease as a comorbidity in the form of asthma (33.3%) or chronic obstructive pulmonary disease (12.8%), and smoking history (59.0%) were more common in those with severe adenoviral infections. With severe disease, 13 (16.7%) required mechanical ventilation, 10 (12.8%) required pressor support, and 2 (2.6%) required extracorporeal membrane oxygenation. Conclusions This retrospective study characterizes severity of adenoviral infections in adult immunocompetent patients, highlights the lack of treatment available, and identifies potential risk factors for severe disease, including asthma, smoking, absence of fever, and presence of coinfection.

A-315 Cardiac Troponin Concentrations in Pediatric Patients Infected with Respiratory Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is associated with considerable morbidity and mortality in pediatric patients. Cardiac troponin I (TnI) has been shown to increase in patients with acute respiratory illness, including COVID-19. The impact of RSV infection on circulating TnI has been formally demonstrated in the literature. The goal of this study was to assess the relationship between TnI and respiratory syncytial virus (RSV) in pediatric patients. Methods A prospective study was conducted at St. Louis Children’s Hospital from October 2023 to February 2024. Patients older than 6 months who presented to the ED and had a CBC ordered within 6 hours of testing positive for RSV on the Biofire® FilmArray® Respiratory Panel were enrolled. Patients with Rhinovirus, Enterovirus, Streptococcus pneumoniae, or Adenovirus infections were included as controls. Remnant EDTA specimens were tested on an Abbott ARCHITECT i2000 for high sensitivity TnI (hs-TnI) with a limit of detection of 1.4 ng/L and a limit of quantitation of 3.5 ng/L. 99% upper reference limits from the CALIPER database on the Abbott of &amp;lt;7 ng/L were used as a threshold for positive results. The electronic medical record (EPIC) was assessed for demographic information and outcomes including length of stay (LOS), intensive care unit (ICU) length of stay, requirement of supplemental oxygen, white blood cell count (WBC), and creatinine. Results A total of 103 patients had RSV and 35 had other respiratory infections (ORI). The average age for the RSV positive group was 2.3 and for the ORI group was 2.4. Males made up 61% of the RSV+ group and 51% of the ORIs. 93 patients in the RSV group were admitted. The median TnI for RSV patients was 1.4 (IQR, 1.2-2.9) and for ORIs was 1.4 (IQR, 1.4-6.8). TnI was measurable in 58% of those with RSV and 54% in ORIs. We next assessed the correlation between hospital LOS and TnI in RSV+ patients, with a Pearson r of 0.42 (95% CI= 0.23-0.58). There was no correlation between WBC and LOS (r=-0.04, 95% CI=-0.25-0.17). There was also no correlation between TnI and WBCs or creatinine. Of admitted patients, 44 (47%) in the RSV group were in the ICU compared to 18 (51.4%) in those with ORIs. RSV+ patients that required ICU treatment had comparable TnI (1.4, IQR, 0.9-3.5) to those that didn’t require ICU stay (1.4, IQR, 0.75-1.5). There was no correlation between ICU LOS and TnI in RSV+ patients (r=-0.08, 95% CI=-0.39-0.24). There was a significant difference in mean TnI concentrations in RSV+ patients that required supplemental oxygen (8.7, 95% CI: 0-19) versus those that did not (1.7, 95% CI: 1.1-2.4). Conclusions There was no difference in TnI in patients hospitalized for RSV relative to ORIs. While TnI concentration was associated with LOS, there were minimally other associations between TnI and outcomes in patients hospitalized with RSV. While TnI elevations are associated with acute respiratory infections in adults, the impact on pediatric patients is not as clear. Future investigation is needed to understand how severe respiratory infections impact pediatric cardiac function.

Epidemiological and clinical characteristics of adenovirus-associated respiratory tract infection in children in Hangzhou, China, 2019-2024.

This study aimed to assess the impact of COVID-19 on the prevalence of adenovirus (AdV) infection in children. This study retrospectively analyzed the changes in the epidemiological and clinical features of AdV-associated respiratory infections in children in Hangzhou, China, between January 2019 and July 2024. A total of 771 316 samples were included in the study, and the positive rate was 6.10% (47 050/771 316). Among them, the positive rate of AdV infection was highest in 2019, reaching 11.29% (26 929/238 333), while the positive rates in the remaining years were between 2% and 9%. In terms of seasonal epidemic characteristics, the summer of 2019 was the peak of AdV incidence, with the positive rate peaking at around 16.95% (7275/45 268), followed by a gradual decline and a low-level epidemic in winter, with a positive rate of 8.79% (8094/92 060). However, during the period 2020-2024, the AdV epidemic season did not show any significant regularity. Gender analysis revealed that the positive rate of male patients was generally greater than that of female patients. In different age groups, the population susceptible to AdV changed before and after the epidemic. In the early and middle stages of the COVID-19 epidemic, the susceptible population was mainly 2-5 years old, whereas in the later stages of the epidemic, the susceptible population was 5-18 years old. In addition, the main clinical symptoms of AdV-positive children from 2019-2024 were respiratory tract symptoms and fever. In summary, the COVID-19 epidemic has had a certain impact on the prevalence of AdV. These findings provide an important basis and reference for the prevention and diagnosis of AdV, especially in the context of increasing age- and gender-specific public health strategies.

Prevalence of Human Adenovirus Type 3 Associated with Pharyngoconjunctival Fever in Children in Osaka, Japan during and after the COVID-19 Pandemic.

The incidence and type distribution of human adenovirus (HAdV) infections among children with pharyngoconjunctival fever (PCF) in Osaka, Japan between 2019 and 2023 were analyzed to assess the effect of the coronavirus disease 2019 (COVID-19) pandemic. The number of reported PCF cases in Osaka decreased from 2020 to 2022, followed by an unprecedented increase in 2023. HAdV-C strains, including types C1, C2, and C5, were detected in throughout the study period. Conversely, HAdV-B3 was not detected for 2 years and 9 months from March 2020 to December 2022, but the number of detections increased from July 2023. Overall, HAdV-B3 was the most frequently detected type (27 of 52 strains), and genetic analysis of its hexon hypervariable regions showed that, except for one strain, the HAdV-B3 strains identified after 2022 had different amino acid substitutions to those identified in 2019 and 2020. These results suggest that the PCF epidemic in 2023 was predominantly caused by variant strains of HAdV-B3, and that children were susceptible owing to a lack of exposure to HAdV-B3 between 2020 and 2022. Ongoing surveillance is needed to evaluate the impact of COVID-19 on the prevalence of HAdV infection.

Detection of Adenovirus Among a Sample of Hemodialysis Patients in Baghdad city

Background: Adenovirus is a DNA virus that was identified in the 1950s from cases of atypical pneumonia in military recruits. Most of the elevated serotype group has been isolated from People who are immunocompromised. While most viral infections are self-limiting, those that affect people with impaired immune systems can be significantly more hazardous and occasionally fatal. Due to increased rates of viral infection, individuals whose renal function has reached its end are suffering from impaired immune responses. The instant study was designed to detect the infection with adenovirus among HD patients in Baghdad city. Objective: To detect of adenovirus in hemodialysis (HD) patients. Methods: In this cross-sectional study, a total of ninety samples patients on maintenance HD attending the Dialysis centers of Al-Kadhimiya Educational Hospital and Al-Yarmouk Teaching Hospital and Al-Shu’ala General Hospital in the period from November 2023 to March 2024. Using enzyme linked immunosorbent assay (ELISA) kit, serum samples were examined for the existence of adenovirus-specific immunoglobulin (IgG) and conformation by using molecular polymerase chain reaction (PCR). Results: Out of 90 hemodialysis patients, the seropositive result for adenovirus-IgG was 41 (68.33). While 16 (26.67) patients were positive by PCR with significant difference (p≤0.01). In addition, 22 (36.67%) patients were males and 19 (31.67%) were females. Conclusions: Patients undergoing HD are susceptible to adenovirus infection, the sero-prevalence of adenovirus in patients considered as risk factor.

Expediting adenovirus titer assays via an algorithmic live-cell imaging technique

Interest in virus-based therapeutics for the treatment of genetic and oncolytic diseases has created a demand for high-yield, low-cost virus-manufacturing processes. However, traditional analytical methods of assessing infectious virus titer require multiple processing steps and manual counting, limiting sample throughput, and increasing human error. This bottleneck severely limits the development of new manufacturing unit operations to drive down costs. In this work, we utilize an Incucyte Live-Cell Analysis System to develop a high-throughput infectious titer assay for adenovirus expressing a GFP-transgene. Although previous studies have demonstrated live-cell imaging’s potential for use with other viruses, they provide little guidance regarding the selection of the viewing and analysis parameters. To fill this gap, we develop an algorithmic approach to identify the optimum viewing and analysis parameters and create a statistical workflow for quantifying infectious adenovirus in a sample dilution series in a standard 24-well microplate. The developed assay is comparable to Hexon staining, the gold-standard for adenovirus infectious titer, with a Pearson correlation coefficient of 0.9. Finally, the developed algorithmic approach and statistical workflow were applied to create an assay for adenovirus titer using a 96-well microplate, allowing five times more samples to be quantified compared to the standard 24-well plate. While this assay uses a GFP-insert that precludes its use in a clinical environment, the key learnings surrounding the careful use of viewing and analysis parameters, and the statistical workflow are widely applicable to implementing life-cell imaging for dilution-series-based assays. Moreover, this method directly enables the fast and accurate evaluation of virus samples in a preclinical environment.

Immune checkpoint inhibitor-induced gastrointestinal injury: prevalence of cytomegalovirus, adenovirus and Epstein-Barr virus

AimsWidespread use of immune checkpoint inhibitors (ICIs) for treatment of advanced malignancies led to an increase in number of immune-related adverse events such as ICI gastrointestinal (GI) injury (ICIGI). The...

High prevalence and genetic heterogeneity of adenoviruses at a psittacine breeding facility.

A polymerase chain reaction (PCR) survey was performed at an amateur parrot breeding facility in Italy to investigate the presence and molecular characteristics of adenoviruses. Eighty psittacine birds, belonging to seven parrot species, were sampled by cloacal swabs; in addition, 15 livers were collected from specimens that were found dead. Seventy-two out of 95 samples collected were positive for adenoviruses, with a prevalence rate of 75.8%. All seven psittacine species tested positive for at least one genus of the family Adenoviridae; notably, adenoviral infection was found for the first time in the hooded parrot (Psephotellus dissimilis). Based on the sequences and phylogenetic analysis, 57 sequences were psittacine adenovirus 2, seven sequences were duck adenovirus 1 and two sequences were identified as psittacine adenovirus 5. The six remaining sequences showed low nucleotide and amino acid identity with the reference strains of accepted species or types, revealing the presence of novel adenoviruses belonging to the genera Aviadenovirus, Barthadenovirus and Siadenovirus. There were identical adenovirus sequences in both apparently healthy and dead birds suggesting that further investigation into the role and impact of these viruses on the health of psittacine birds is warranted.