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Concepción Santacruz Valdés,1 Efrén Raúl Ponce-Rosas,2 Maria C Jimenez-Martinez3,4 1Department of Cornea and Refractive Surgery, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico; 2Subdivision of Family Medicine, Department of Postgraduates, Faculty of Medicine, National Autonomous University of México, Mexico City, Mexico; 3Department of Immunology and Research Unit, Institute of Ophthalmology “Conde de Valenciana”, Mexico City, Mexico; 4Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, MexicoCorrespondence: Maria C Jimenez-Martinez, Email mcjimenezm@facmed.unam.mxIntroduction: Acute adenoviral conjunctivitis is a disease with mild to severe clinical manifestations. Animal models have provided insight into the role of the innate immune system in clinical damage, but the human immune response at the ocular surface remains poorly understood. Therefore, this study aimed to establish the relationship between tear cytokine levels and disease severity in patients with epidemic keratoconjunctivitis (EKC).Methods: Fourteen consecutive patients with EKC, confirmed with HAdV8 infection, were included. Ocular characteristics were documented, and each patient’s eye was classified as having more or less severe disease. After tear sampling, levels of cytokines IL-8, IL-6, IL-1b, IL-10, IL-12, and TNF-a were measured using a cytometric bead array.Results: Our results showed the expression of proinflammatory cytokines in EKC-affected eyes. IL-6, IL-8, and IL-12 significantly correlated with the total clinical ophthalmological score. In the more severely affected eyes, IL-8 and IL-6 significantly correlated with conjunctival hyperemia, and IL-6 correlated with conjunctival swelling. In the less severely affected eyes, inflammatory response, conjunctival hyperemia, and conjunctival hemorrhages were significantly correlated with IL-12 and TNF-a, and ocular discharge was significantly correlated with all tear cytokines. IL-10 was detected in both eyes, suggesting a possible regulatory counterbalance.Discussion: This study offers novel insights into the pathophysiology of human adenoviral keratoconjunctivitis and its association with clinical data.Plain language summary: Despite the clinical significance of adenoviral keratoconjunctivitis, most studies have concentrated on defining its genotype. Similarly, knowledge of the molecular basis of adenoviral conjunctivitis comes from animal models or cellular lines. Prior to our work, the human immune response at the ocular surface during adenovirus conjunctivitis was poorly understood. Our study described the clinical features of the disease based on severity and found significant correlations between proinflammatory tear cytokines and clinical signs. The results of this study provide new insights into the pathophysiology of adenoviral keratoconjunctivitis and a potential new approach to diagnosis and prompt treatment.Keywords: tear cytokines, adenovirus infection, keratoconjunctivitis, IL-1b, IL-6, IL-8, IL-10, IL-12, TNF-a

Adenovirus infection in dogs caused by canine adenovirus serotype 2 predominantly results in respiratory disease typically manifested by respiratory tract lesions. Infectious laryngotracheitis is the most often recorded in dogs in the central part of the Russian Federation and its incidence tends to increase. Therefore, preventive immunization against this disease remains important. Primarily, the virus strains currently important and circulating in the particular territory shall be used for vaccine production to induce long-term and strong immunity in animals. The study was aimed at isolation of canine adenovirus type 2 remaining stable during five or more passages from the biological samples collected from animals with adenovirus infection signs as well as at determination of its cultivation parameters. As a result, five virus isolates were recovered, one of the recovered virus isolates had optimal properties for its use for vaccine production. Comparative analysis of continuous Vero, MDCK (NBL-2 and NBL-9 line) cell cultures as well as primarily trypsinized cell cultures (baby dog kidney, baby dog spleen, baby cat kidney, baby cat spleen) for their susceptibility to the recovered virus showed that MDCK (NBL-2 line) was the most susceptible. The virus cultivation parameters in this cell culture was determined at the next step. The following optimal conditions under which the virus accumulated to the maximum titres were determined: cell culture monolayer age for inoculation – 48 hours, multiplicity of infection – 0.01 TCID50/cell, preliminary holding time – 60 min, temperature – (37.0 ± 0.5) °С, cultivation period – 120 hours.

Abstract Background Human 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. Methods This 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. Results The 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. Conclusion Our 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.

Background/aim: Differentiating multisystem inflammatory syndrome in children (MIS-C) from adenovirus infection (AI) can be challenging due to similar clinical and laboratory findings. This study aimed to identify distinguishing characteristics and develop a scoring system to facilitate accurate diagnosis. Materials and methods: A comprehensive review of medical records was undertaken for 108 MIS-C patients and 259 patients with confirmed AI. A comparison of laboratory data and clinical findings was conducted across the patient groups using appropriate statistical tests. Results: The MIS-C patients were significantly older than the AI patients (p < 0.001). Diarrhea, rash, abdominal pain, vomiting, nonexudative conjunctivitis, lymphadenopathy tachycardia, bradycardia, hypotension, hypoxia seizures, agitation, headache, and altered consciousness symptoms were more frequently associated with MIS-C (p < 0.001), while cough and runny nose were significantly more common in AI (p < 0.001). Lymphopenia and thrombocytopenia were more prevalent in the MIS-C patients (p < 0.001). AI and MIS-C were scored by giving one point each to the parameters that created the difference. For AI, being =60 months of age, the presence of cough, runny nose and absence of diarrhea, rash, abdominal pain, vomiting, nonexudative conjunctivitis, lymphadenopathy, tachycardia, bradycardia, hypotension, hypoxia seizures, agitation, headache, and altered consciousness, lymphopenia, thrombocytopenia, and C-reactive protein value <124.5 mg/L were determined as each parameter plus one point. A total score above 14 could predict AI with a high degree of accuracy, with sensitivity at around 97.5% and specificity at 92.6%. Conclusion: The proposed inpatient scoring system, when used in conjunction with polymerase chain reaction testing, may improve the early differentiation of AI and MIS-C. This approach could help reduce unnecessary testing and optimize resource allocation. Further research with larger samples should investigate this novel scoring system to establish its reliability and generalizability. [ABSTRACT FROM AUTHOR]

Background: Human 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. Methods: This 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. Results: The 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. Conclusion: Our 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. [ABSTRACT FROM AUTHOR]

ABSTRACT Viruses display large variability across all stages of their life cycle, including entry, gene expression, replication, assembly, and egress. We previously reported that the immediate early adenovirus (AdV) E1A transcripts accumulate in human lung epithelial A549 cancer cells with high variability, mostly independent of the number of incoming viral genomes, but somewhat correlated to the cell cycle state at the time of inoculation. Here, we leveraged the classical Luria–Delbrück fluctuation analysis to address whether infection variability primarily arises from the cell state or stochastic noise. The E1A expression was measured by the expression of green fluorescent protein (GFP) from the endogenous E1A promoter in AdV-C5_E1A-FS2A-GFP and found to be highly correlated with the viral plaque formation, indicating reliability of the reporter virus. As an ensemble, randomly picked clonal A549 cell isolates displayed significantly higher coefficients of variation in the E1A expression than technical noise, indicating a phenotypic variability larger than noise. The underlying cell state determining infection variability was maintained for at least 9 weeks of cell cultivation. Our results indicate that preexisting cell states tune adenovirus infection in favor of the cell or the virus. These findings have implications for antiviral strategies and gene therapy applications.IMPORTANCEViral infections are known for their variability. Underlying mechanisms are still incompletely understood but have been associated with particular cell states, for example, the eukaryotic cell division cycle in DNA virus infections. A cell state is the collective of biochemical, morphological, and contextual features owing to particular conditions or at random. It affects how intrinsic or extrinsic cues trigger a response, such as cell division or anti-viral state. Here, we provide evidence that cell states with a built-in memory confer high or low susceptibility of clonal human epithelial cells to adenovirus infection. Results are reminiscent of the Luria–Delbrück fluctuation test with bacteriophage infections back in 1943, which demonstrated that mutations, in the absence of selective pressure prior to infection, cause infection resistance rather than being a consequence of infection. Our findings of dynamic cell states conferring adenovirus infection susceptibility uncover new challenges for the prediction and treatment of viral infections.

Outbreaks of fowl adenovirus (FAdV) infection in chicken flocks in Poland threaten birds’ health and lives and are rising in frequency. The risk of these infections in immunocompromised poultry flocks with developed clinical symptoms was analysed through virus detection in broiler chicks and correlation of cases with the birds’ immune strength.

Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action's chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs. [ABSTRACT FROM AUTHOR]

Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action’s chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs.

Adenovirus (AdV) infection occurs in 0–20% of patients in the first 3–4 months after allogeneic hematopoietic cell transplantation (HCT), being higher in pediatric than in adult patients. About 50% of AdV infections involve the blood, which in turn, correlates with an increased risk developing AdV diseases, end‐organ damage, and 6‐month overall mortality. The main risk factors for AdV infection are T‐cell depletion of the graft by ex vivo selection procedures or in vivo use of alemtuzumab or antithymocyte serum, development of graft versus host disease (GVHD) grade III–IV, donor type (haploidentical or human leucocyte antigen mismatched related donor > cord blood> unrelated matched donor) and severe lymphopenia (<0.2 × 109/L). The prevention of AdV disease relies on early diagnosis of increasing viral replication in blood or stool and the pre‐emptive start of cidofovir as viral load exceeds the threshold of ≥102–3 copies/mL in blood and/or 106 copies/g stool in the stool. Cidofovir (CDV), a cytosine monophosphate nucleotide analog, is currently the only antiviral recommended for AdV infection despite limited efficacy and moderate risk of nephrotoxicity. Brincidofovir, a lipid derivative of CDV with more favorable pharmacokinetics properties and superior efficacy, is not available and currently is being investigated for other viral infections. The enhancement of virus‐specific T‐cell immunity in the first few months post‐HCT by the administration of donor‐derived or third‐party‐donor‐derived virus‐specific T‐cells represents an innovative and promising modality of intervention and data of efficacy and safety of the ongoing prospective randomized studies are eagerly awaited. [ABSTRACT FROM AUTHOR]

Adenovirus (ADV) may cause severe complications in hematopoietic stem cell transplant recipients, but disseminated ADV infections in patients who received chemotherapy alone for hematological malignancies are poorly understood due to the rarity of cases. Concomitant infection with Pneumocystis (PCP) is extremely rare. Despite being diagnostically challenging, a more specific workup needs to be initiated with a low threshold in patients who are exposed to agents with the potential to suppress T cells. We report a fatal case of disseminated ADV and drug‐resistant PCP pneumonia in a patient with mantle cell lymphoma who had only received combination chemotherapy. A 75‐year‐old man who was diagnosed with mantle cell lymphoma 10 months prior was admitted for mild hypoxic respiratory failure. Bendamustine, Rituximab, Cytarabine regimen had resulted in complete remission of his lymphoma, with the last cycle of chemotherapy administered 3 months prior to admission. CT of the chest revealed ground‐glass opacities concerning pneumonia. Initial laboratory tests were remarkable for mild leukopenia. The respiratory viral panel was only positive for ADV. He did not respond to empiric antibiotics for community‐acquired pneumonia and Trimethoprim / Sulfamethoxazole given later for positive Beta D Glucan (BDG) suggestive of Pneumocystis pneumonia. Then, he developed hemorrhagic cystitis, followed by liver and renal function derangement that prompted checking serum ADV viral load by polymerase chain reaction (PCR). This test took 1 week to return, with a viral load of 50, 000 copies/mL suggesting disseminated ADV infection. Despite initiation of Cidofovir, multi‐organ failure continued to progress, and the follow‐up viral load had doubled on Day 2. The patient passed away the same day shortly after transition to comfort care. T cell suppression seems to be a risk factor for disseminated ADV disease. Clinicians may need to maintain a low threshold to send serum quantitative ADV PCR when symptoms are not improved by antimicrobial treatment for more conventional infections in patients who received agents that are known to suppress T cells, such as Bendamustine. [ABSTRACT FROM AUTHOR]

The article presents a clinical observation of severe acute hepatitis of unknown aetiology with liver transplantation in a 16-year-old child, which occurred in October 2021. Initial symptoms were abdominal pain, diarrhea. The general wellbeing of the girl did not suffer, there was no fever, no intoxication syndrome. Over the next days, she began to notice the appearance of edema on the legs, an increase in the size of the abdomen. From the 10-11th day of illness – darkening of urine, acholia of feces, jaundice were observed. She was examined by a pediatrician, a biochemical blood test was performed, according to the results the girl was hospitalized with a diagnosis of acute hepatitis. According to the severity of the condition, she was hospitalized in the ICU. On admission she complained of abdominal pain, jaundice, edema, and weakness. On examination: jaundice, scleral icterus, hemorrhagic rash at the site of the tourniquet, bleeding from injection sites, hepatomegaly, anasarca. In blood tests: progressive anemia, thrombocytopenia, increased AST (with a decrease in dynamics against the background of progression of liver failure), a decrease in total protein and albumin, fibrinogen, prothrombin according to Quick. Laboratory excluded viral hepatitis A-E. The only infectious agent diagnosed was group F adenovirus in feces. By the third day of hospitalization developed of multiple organ failure, DIC. On the 4th day of hospitalization, the child was transferred to a specialized hospital, where an emergency liver transplantation was performed. The operation was successful, the child was discharged in a stable condition.

Exocrine pancreatic insufficiency (EPI) is suspected but remains understudied in immunosuppressed conditions such as post-hematopoietic stem cell transplantation (HSCT). This prospective observational study aimed to investigate the incidence, impact, and risk factors of EPI in a cohort of 83 pediatric and young adult patients who underwent allogeneic HSCT at Charité - Universitätsmedizin Berlin between 2020 and 2023. Fecal pancreatic elastase (PE) measurements and transabdominal ultrasound were utilized to evaluate pancreatic function over a one-year period. Secondary analysis explored the association of EPI with clinical complications and included a multivariable regression analysis of potential risk factors. Low PE levels significantly correlated with pathological pancreatic imaging findings, independent of concurrent diarrhea. EPI was suspected in 45% (32/71) of patients (95%CI: [34.1%, 56.6%]), with 29% (13/45) (95%CI: [17.7%, 43.4%]) showing signs of prolonged EPI (pEPI) lasting at least 8 weeks. After excluding cases with confounding factors such as missing enteral nutrition and diarrhea, the cumulative incidence of prolonged EPI was 20% (8/41) (95%CI: 10.2%-34.0%) in the overall cohort. EPI was associated with weight loss, prolonged dependence on parenteral nutrition, and extended hospitalizations. Adenovirus (ADV) infection emerged as a significant risk factor for EPI (hazard ratio 3.22 [95%CI:1.26-8.2], p = 0.014), along with additional factors such as higher BMI pre-HSCT, pre-existing pancreatic damage and early post-HSCT fasting. The persistence of pancreatic atrophy and EPI beyond two years post-HSCT in individual cases suggests a potential for permanent pancreatic damage. This study underscores that EPI is a common complication following HSCT, with ADV infection being an important risk factor. The findings support routine PE measurements and early initiation of pancreatic enzyme replacement therapy (PERT), alongside aggressive treatment of ADV infections. Further research is necessary to evaluate the effects of PERT in this population and to explore the applicability of these findings in other immunosuppressed groups., (© 2025 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The diagnostic potential of the 4B7 and 6B12 monoclonal antibodies (MAbs) against human adenovirus hexon protein has been studied in various immunological tests, namely, the in-cell enzyme-linked immunosorbent assay (cell-ELISA), sandwich ELISA, and the immunofluorescence antibody technique (IFA). It was shown that the sensitivities of cell-ELISA, sandwich ELISA, and IFA were 96, 86, and 84%, respectively, compared to PCR. Thus, 4B7 and 6B12 MAbs are promising immunoreagents for the construction of various diagnostic kits to use in laboratory practice for adenovirus detection in clinical samples. [ABSTRACT FROM AUTHOR]

Human Adenovirus (HAdV) infection occurs in 14–16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk of developing HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical, or HLA mismatched parent), and severe lymphopenia (<0.2 × 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold in the blood (≥102–3 copies/mL) and/or in the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3–5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention, applicable both in prevention and therapeutic settings. [ABSTRACT FROM AUTHOR]

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Objectives: To explore the characteristics of Kawasaki disease (KD) under 6 months and to investigate the possible indications of incomplete KD (iKD).Methods: The medical records of KD patients hospitalized in Children's Hospital of Soochow University from January 2007 to December 2017 were retrospectively reviewed and analyzed. A total of 50 cases of urinary tract infection (UTI) and 50 cases of adenovirus (ADV)-infected patients under 6 months that were age and gender-matched with the main complaint of high fever were selected as controls.Results: A total of 1,872 KD patients were enrolled. Among them, 194 (10.4%) were infantile patients under 6 months. There were 72 (37.1%) and 494 (29.4%) iKD in patients younger and older than 6 months, respectively (P < 0.05). Although patients under 6 months had a shorter fever duration before immunoglobulin (IVIG) treatment, a larger proportion of these patients had IVIG resistance and coronary artery lesions. They also tended to have higher platelet (PLT) counts and C-reactive protein (CRP) and lower hemoglobin (Hb), percentage of neutrophils (N%), albumin and serum sodium. When we compared iKD under 6 months with UTI and ADV-infected patients, significant differences were found in white blood cells (WBC), Hb, PLT, CRP, N% and serum albumin (P < 0.05). After adjusting the confounders, Hb < 105.5 g/L, CRP > 22.7 mg/L, N% > 47.4 and PLT > 496 × 109/L were indications of iKD when compared with ADV infection (area under the curve [AUC]: 0.872, 0.939, 0.707, and 0.684, respectively). N% > 51.8 and albumin < 39.0 g/L were indications of iKD when compared with UTI (AUC: 0.627 and 0.832, respectively).Conclusions: Infantile KD patients under 6 months had their own particularity. Laboratory variables could be good indications of iKD when compared with UTI and ADV infection.

Human adenoviruses (HAdVs) have been demonstrated to cause a diversity of diseases among children and adults. The circulation of human adenovirus type 21 (HAdV21) has been mainly documented within closed environments in several countries. Nonetheless, respiratory infections or outbreaks due to HAdV21 have never been reported in China. MinION and Illumina platforms were employed to identify the potential pathogen from a throat swab. Discrepancies between MinION and Illumina sequencing were validated and corrected via polymerase chain reaction (PCR). Genomic characterization and recombinant event detection were then performed. Among the 35,466 high-quality MinION reads, a total of 5,999 reads (16.91%) could be aligned to HAdV21 reference genomes (genome sizes ≈35.3 kb), among which 20 had a length of >30 kb. A genome sequence assembled from MinION reads was further classified as HAdV subtype 21a. Random downsampling revealed as few as 500 nanopore reads could cover ≥96.49% of current genome. Illumina sequencing displayed good consistency (pairwise nucleotide identity = 99.91%) with MinION sequencing but with 31 discrepancies that were further validated and confirmed by PCR coupled with Sanger sequencing. Restriction enzymes such as BamHI and KpnI were able to distinguish the present genome from HAdV21 prototype and HAdV21b. Phylogenetic analysis employing whole-genome sequences placed our genome with members only from subtype 21a. Common features among HAdV21a strains were identified, including polymorphisms discovered in penton and 100 kDa hexon assembly–associated proteins and a recombinant event in the E4 gene. Using MinION and Illumina sequencers, we identified the first HAdV21a strain from China, which could provide key genomic data for disease control and epidemiological investigations.

Background: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT).Methods: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models.Results: Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52-3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83-4.75) correlated with mortality at D +180.Conclusions: In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HAdVs) have been demonstrated to cause a diversity of diseases among children and adults. The circulation of human adenovirus type 21 (HAdV21) has been mainly documented within closed environments in several countries. Nonetheless, respiratory infections or outbreaks due to HAdV21 have never been reported in China. MinION and Illumina platforms were employed to identify the potential pathogen from a throat swab. Discrepancies between MinION and Illumina sequencing were validated and corrected via polymerase chain reaction (PCR). Genomic characterization and recombinant event detection were then performed. Among the 35,466 high-quality MinION reads, a total of 5,999 reads (16.91%) could be aligned to HAdV21 reference genomes (genome sizes ≈35.3 kb), among which 20 had a length of >30 kb. A genome sequence assembled from MinION reads was further classified as HAdV subtype 21a. Random downsampling revealed as few as 500 nanopore reads could cover ≥96.49% of current genome. Illumina sequencing displayed good consistency (pairwise nucleotide identity = 99.91%) with MinION sequencing but with 31 discrepancies that were further validated and confirmed by PCR coupled with Sanger sequencing. Restriction enzymes such as Bam HI and Kpn I were able to distinguish the present genome from HAdV21 prototype and HAdV21b. Phylogenetic analysis employing whole-genome sequences placed our genome with members only from subtype 21a. Common features among HAdV21a strains were identified, including polymorphisms discovered in penton and 100 kDa hexon assembly–associated proteins and a recombinant event in the E4 gene. Using MinION and Illumina sequencers, we identified the first HAdV21a strain from China, which could provide key genomic data for disease control and epidemiological investigations. [ABSTRACT FROM AUTHOR]

A 35-year-old female with no medical history presented with fever. Laboratory work was normal except for elevated liver function test (LFT): alkaline phosphatase (AP) (296), aspartate transaminase (AST) (343), alanine transaminase (ALT) (378), and international normalized ratio (INR) (1.23). Ultrasound liver was normal. Infectious workup was negative for hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus (HEV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes simplex virus (HSV), and COVID-19. Similarly, autoimmune hepatitis, Wilson, and alpha-1 antitrypsin workup were negative. She reported taking Yogi-Kanthika (ayurvedic-proprietary medicine) on/off for seasonal sore throat, yet RUCAM-score was 2 (unlikely a drug induced injury). Respiratory-viral-panel came positive for adenovirus. With supportive treatment, symptoms and LFT trended down, thus, liver biopsy decision was deferred. We believe this is the first reported case of adenovirus hepatitis in an immunocompetent adult. Hence, we suggest that clinicians should consider a refined differential diagnosis for elevated LFT (that includes adenovirus). [ABSTRACT FROM AUTHOR]

In the infectious pathology of childhood, viral diarrhea becomes increasingly important. In the present work, the clinical and epidemiological features of rotavirus, adenovirus, norovirus and enterovirus enteric infections in children have been analyzed. It was found that viral intestinal infections are one of the leading causes of infectious gastroenteritis in infants. Viral diarrhea is most severe in children with unfavorable premorbid background. Infant patients are characterized by the development of water-deficient excoxicosis. The absence of specific prevention, ease introduction of infection creates the prerequisites for the growth of morbidity.

The research goal is to study the performance of INF-а, INF-y and IL-1(3 in children with acute respiratory viral infection (ARVI) depending on etiology, the presence of mixed infection, disease severity, presence of complications, the concentration of thyroid hormones. Material and Methods. Examined 147 patients aged from 1 to 10 years at the outbreak of the ARVI and 15 healthy children. Patients in the midst of acute respiratory infections was conducted to determine levels of IL-1(3, INF-а, INF-y, triiodothyronine (T3) and free thyroxine free (T4) by ELISA using standard test kits JSC "Vector-best" (Koltsovo, Novosibirsk region). Results. It was showed elevated level of INF-y in patients with PC-infection in comparison with the same indicator in healthy children. Set the increased level of INF-а in severe ARVI and the level of INF-y at medium severe form. It was showed increased levels of INF-y in patients with mixed infection. In children with complications, the level of IL-1 (3 was lower almost in 2.4 times, than in children without complications. Among patients with complications, the highest numbers of INF-а were detected in children with pneumonia and INF-y increased in patients with bronchitis. When conducting correlation analysis, the highest rates of INF-а were observed in children with the syndrome of "low T3", and INF-y in children as low T3 and low T4. Conclusion. An increase in the level of INF-y in patients with RS infection was found. Revealed that in children in acute period of SARS levels IL-1 IS, INF-а do not depend on the etiological factor of SARS. These indicators are influenced by the severity of the disease, which in our study was due to the development of mixed infection, the presence and nature of complications. High rates of INF-а and INF-y have significant inverse correlation with the level of T3, which reflects the degree of intoxication in the acute period of infectious diseases.

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 283 days 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. [ABSTRACT FROM AUTHOR]

Aminopeptidase N (ANPEP) is a membrane-bound zinc-dependent peptidase. Although it is widely believed that ANPEP acts as an important angiogenesis regulatory factor, there are few studies about its function in the female reproductive system. In our previous research, we applied Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) to analyze the influence of different controlled superovulation treatments for Assisted Reproductive Technology, In Vitro Fertilization and Embryo Transfer (IVF-ET)) patients from a global proteomic perspective to search for potential biomarkers associated with endometrium receptivity and embryo implantation. ANPEP is one of the proteins that demonstrated differential expression between different treatment groups and may be closely associated with endometrial receptivity. In this study, we assessed the expression of ANPEP in the endometrium of mice at different ages and found it to be highest in the mature period. We also detected ANPEP expression in the endometrium of IVF-ET patients in the proliferative, preimplantation and implantation stages, and the highest expression level of ANPEP was found in the last group. Human primary endometrial stromal cells were infected with an adenovirus expression vector containing the ANPEP gene and a green fluorescent protein (GFP) fusion protein; the mRNA levels of HOXA-10, LIF, and integrin β3 were found to be increased. Therefore, we conclude that ANPEP could be involved in the regulation of endometrial receptivity. • The present study highlights ANPEP expressed in the endometrium could be involved in regulating endometrial receptivity. • ANPEP in mouse and human endometrium increases with the improvement of reproductive ability. • Some important endometrial receptivity factors in human endometrial cells increase with ANPEP upregulation. [ABSTRACT FROM AUTHOR]

Background. The ratio of adenovirus disease in the structure of acute respiratory viral infections is substantial, and this group of infections annually makes up to 30 % of general infectious morbidity rate. Today, the peculiarities of heterospecific anti-infectious defense are understudied in patients with adenovirus infection. The aim: to study the reactive response of polimorphonuclear granulocytes of the peripheral blood in adult patients with adenovirus infection. Materials and methods. This case-control study involved 37 young volunteers with the signs of acute respiratory viral infection in the moment of appeal to practitioner (based on the criteria of unified protocol). We have analyzed the absolute and relative amounts of basic populations of immunocompetent cells of the peripheral blood, conducted the calculation of immune-haematological indexes characterizing the reactive response of basic cells of heterospecific immunity. Results. An inflammatory process is associated with the increase in the absolute amount of leucocytes by 19.76 %, band neutrophils — by 2.18 times; lymphocytes — by 30.30 % and monocytes — by 48.15 %. The increase in the reactivity of neutrophilic granulocytes by 83.92 % was detected that indicates the activation of these cells by the system of cytokines in heterospecific anti-infectious defense, and that is why its general activity increases by 12.62 %. Conclusions. The above mentioned testifies the forming of different types of immune response to adenovirus antigens. A specific immune response is formed later, that is confirmed by the decrease in the index of immunological reactivity of patients’ body by 14.86 %. Methodology for the estimation of the reactive response of neutrophils can be used in practical work of doctors for early prognostication of possible changes in the system of anti-infectious defense of patients’ body.

During a 2014 measles outbreak in Vietnam, postmortem pathologic examination of hospitalized children who died showed that adenovirus type 7 pneumonia was a contributory cause of death in children with measles-associated immune suppression. Adenovirus type 7 pneumonia should be recognized as a major cause of secondary infection after measles.

Purpose. To evaluate the clinical efficacy of a combined application of Okomistin and Oftalmoferon compared to an Oftalmoferon monotherapy in the treatment of viral conjunctivitis. Material and methods. We observed 38 patients with various forms of clinical progression of viral eye diseases: adenoviral conjunctivitis (AVC) – 26 patients, shipyard disease – 12 patients. The patients’ age ranged from 19 to 68 years. Okomistin and Oftalmoferon eye drops were used as basic drugs according to the following scheme: Okomistin followed by Oftalmoferon in 10-15 minutes. Instillations repeated 8-10 times a day. Since the 5th day of treatment the instillations were reduced up to 6 times a day, and then to 4 times daily. Results. During this therapy for the AVC periods of conjunctiva normalization with disappearance of inflammatory effects decreased up to 6.2 days. In case of shipyard disease in administration of combined therapy with the Okomistin + Oftalmoferon medicine the treatment period lasted 12.3 days. The positive therapeutic effect was observed in 96% of cases.Conclusions. The combined use of Okomistin and Oftalmoferon compared to the Oftalmoferon monotherapy in the treatment of viral conjunctivitis has a more pronounced therapeutic effect.

Among respiratory infections, adenovirus infection (ADVI), in the presence of which there may be severe pneumonia that frequently results in a fatal outcome, occupies particular attention. ADVI in patients without immunodeficiency is usually mild and shows a limited extent of injury. At the same time the disease in immunocompromised individuals may be severe, presenting with viremia, evolving sepsis, and high death rates. The paper gives a characteristic example of severe ADVI and its fatal outcome.

Aim. Study prevalence of adenovirus species and serotypes that had caused acute respiratory viral infection (ARVI) in Moscow in 2004 - 2014. Materials and methods. Material from respiratory tract of4731 patients with ARVI and 663 conditionally healthy children and adults was used. ARVI causative agents were detected by PCR with real-time detection using AmpliSens reagent kits (CRIE, Moscow). Membership of adenoviruses to a certain serotype was determined by sequencing of hexon gene segment. Adenoviruses that had caused ARD in servicemen in 2010 - 2014 were also studied. Results. ARVI causative agents were detected in 64.6% ill children and 58% of adults. Respiratory-syncytial and rhinoviruses prevailed in children, influenza A virus - in adults. Adenoviruses were detected in 6.9% of ill children and 2.9% of adults during the whole year, with a rise in October-December. B and C species occurred at an equal frequency, E species was found less often. Serotypes 3 and 2 prevailed in 34% and 21% of cases of adenovirus mono-infection, respectively, serotypes 7, 6 and 4 occurred less often. 4 out of 5 outbreaks of adenovirus infection in servicemen were caused by serotype 7. Adenoviruses were absent in the group of healthy adults, in conditionally healthy children were detected in 0.4% of cases and were attributed to serotypes 1 and 2. Conclusion. Etiological structure of ARVI was studied for the last decade. Adenovirus infection ranked 5th in children and 7th in adults. 9 serotypes of 3 species of respiratory adenoviruses were identified. Varying prevalence of species and serotypes depending in season, clinical diagnosis and patient age was demonstrated.

Summary: The important insights gained over the past years in diagnosis and treatment of invasive adenoviral infections provide new paradigms for the monitoring and clinical management of these life‐threatening complications. A meeting was held to discuss and subsequently disseminate the current advances in our understanding of the aetiology/pathogenesis and future treatment options facilitating effective control or prevention of adenovirus‐related diseases in the allogeneic haematopoietic stem cell transplant setting. Invited experts in the field discussed recent progress with leading members of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation at the “State‐of‐the‐art” Meeting in Poznan, Poland, in October 2017. In this review article, the panel of experts presents a concise summary of the current evidence based on published data from the last 15 years and on recent achievements resulting from real‐life practice. The present position statement reflects an expert opinion on current approaches to clinical management of adenovirus infections in patients undergoing allogeneic haematopoietic stem cell transplant and provides graded recommendations of the panel for diagnostic approaches and preemptive therapy reflecting the present state of knowledge. [ABSTRACT FROM AUTHOR]