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BMC Infectious Diseases May 2024Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic...
Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic diversity and epidemiology of HAdVs in Pakistan. This study characterized HAdVs in pediatric patients with respiratory tract infections in Karachi, Pakistan, between 2022 and 2023. We analyzed 762 nasopharyngeal samples of children ≤ 5 years. DNA extraction, followed by PCR targeting E2B and hexon genes, was carried out. Data analysis was performed on SPSS 25.0, and phylogenetic analysis of hexon gene was performed on MEGA 11. HAdV was detected in 7.34% (56/762) of patients round the year, but at a significantly higher rate during the winter season. Age was insignificantly associated with HAdV incidence (p = 0.662), but more than 62.5% (35/56) of positive cases were younger than 10 months. The circulating HAdVs were identified as six different types from species B (78.57%) and C (21.42%), with the majority of isolates found to be like B3. HAdV was found to be co-infected with bocavirus (5.4%) and measles (7.14%). These findings revealed a high frequency and genetic diversity of respiratory HAdVs in Karachi, Pakistan. We conclude that periodic and continuous surveillance of adenoviruses and other respiratory pathogens is necessary to improve the prognosis and management of respiratory diseases, thereby reducing the child mortality rate in Pakistan.
Topics: Humans; Pakistan; Adenoviruses, Human; Respiratory Tract Infections; Child, Preschool; Infant; Phylogeny; Male; Female; Adenovirus Infections, Human; Nasopharynx; Genetic Variation; Infant, Newborn; Coinfection; DNA, Viral; Seasons; Genotype
PubMed: 38811902
DOI: 10.1186/s12879-024-09415-9 -
Sisli Etfal Hastanesi Tip Bulteni 2024This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to...
OBJECTIVES
This study aims to determine the risk factors by examining the sociodemographic characteristics of infants hospitalized in the neonatal intensive care unit (NICU) due to lower respiratory tract infection (LRTI), to determine the factors that affect the duration of hospitalization, and to determine the underlying microbial factors and evaluate them in the light of the literature.
METHODS
This study evaluated the data of newborns hospitalized with LTRI between 01 October 2022 and 31 March 2023. Demographic characteristics of the patients detected viral agents, duration of hospitalization and risk factors were recorded in the study form. Babies divided viral LRTI and non-viral LRTI, and then compared with each other. Additionally, the facts that might affect the duration of hospitalization were investigated.
RESULTS
The study included 57 babies. Viral agent was detected in 50.9% of the babies, the most frequently viral agent was respiratory syncytial virus (RSV) (48.2%). Other viral factors, in order of frequency; Adenovirus, SARS-CoV-2, Influenza A and B. There is no demographic difference between the viral agent positive and negative groups. The patients were evaluated according to length of hospitalization, it was seen that the hospital stay was longer in babies who were found to be viral positive and needed oxygen therapy (p=0.02, p=0.03, respectively). The male gender ratio was higher in the group with longer hospital stays, but this difference was not statistically significant. Although the rate of exclusive breastfeeding was higher in the group with a short hospitalization period, this difference was not statistically significant (p>0.05).
CONCLUSION
RSV is currently the most frequently detected viral agent in lower respiratory tract infections in newborns. The hospital stay of babies diagnosed with RSV is longer than those with non-RSV viral agents. So struggling with RSV is important in preventing lower respiratory tract infections in newborns. It is necessary to develop a vaccine or immunoglobulin application against RSV infection not only for preterm babies but also for all newborn babies.
PubMed: 38808041
DOI: 10.14744/SEMB.2023.77674 -
Veterinary World Apr 2024Live-attenuated vaccines are the most successful type of vaccine and could be useful in controlling fowl adenovirus (FAdV) 8b infection. This study aimed to attenuate,...
BACKGROUND AND AIM
Live-attenuated vaccines are the most successful type of vaccine and could be useful in controlling fowl adenovirus (FAdV) 8b infection. This study aimed to attenuate, molecularly characterize, and determine the immunogenicity, efficacy, and challenge virus shedding in broiler chickens.
MATERIALS AND METHODS
The FAdV 8b isolate (UPM08136) was passaged onto chicken embryo liver (CEL) cells until attenuation. We sequenced and analyzed the hexon and fiber genes of the passage isolates. The attenuated bioreactor-passage isolate was inoculated into 1-day-old broiler chickens with (attenuated and inactivated) and without booster groups and challenged. Body weight (BW), liver weight (LW), liver: body weight ratio (LBR), FAdV antibody titers, T-lymphocyte subpopulation in the liver, spleen, and thymus, and challenge virus load and shedding were measured.
RESULTS
Typical cytopathic effects with novel genetic changes on CEL cells were observed. The uninoculated control-challenged (UCC) group had significantly lower BW and higher LW and LBR than the inoculated groups. A significantly higher FAdV antibody titer was observed in the challenged non-booster and attenuated booster groups than in the UCC group. T cells in the spleen and thymus of the liver of inoculated chickens were higher than uninoculated control group levels at all-time points and at different times. A significantly higher FAdV challenge virus load was observed in the liver and shedding in the cloaca of UCC chickens than in non-booster chickens.
CONCLUSION
The FAdV 8b isolate was successfully attenuated, safe, and immunogenic. It reduces virus shedding and is effective and recommended as a vaccine against FAdV infection in broiler chickens.
PubMed: 38798289
DOI: 10.14202/vetworld.2024.744-755 -
BMC Pulmonary Medicine May 2024The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in high-risk patients with haematological malignancies (HM) is uncertain. We aimed to examine how community-acquired pneumonia aetiology in patients with haematological malignancies changed during the COVID-19 pandemic.
METHODS
This was a retrospective study that included 524 patients with haematological malignancies hospitalised with community-acquired pneumonia between March 2018 and February 2022. Patients who underwent bronchoscopy within 24 h of admission to identify community-acquired pneumonia aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and polymerase chain reaction tests were analysed and compared to identify changes and in-hospital mortality risk factors.
RESULTS
Patients were divided into the 'pre-COVID-19 era' (44.5%) and 'COVID-19 era' (55.5%) groups. The incidence of viral community-acquired pneumonia significantly decreased in the COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (pre-COVID-19 era vs. COVID-19 era: 3.0% vs. 0.3%, P = 0.036; 6.5% vs. 0.7%, P = 0.001; 5.6% vs. 1.4%, P = 0.015; and 9.5% vs. 1.7%, P < 0.001, respectively), whereas that of bacterial, fungal, and unknown community-acquired pneumonia aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet counts correlated with in-hospital mortality after adjusting for potential confounding factors.
CONCLUSIONS
In the COVID-19 era, the incidence of community-acquired pneumonia with viral aetiologies markedly decreased among patients with haematological malignancies, with no changes in the incidence of bacterial and fungal pneumonia. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with haematological malignancies and community-acquired pneumonia.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Hematologic Neoplasms; Middle Aged; Community-Acquired Infections; Aged; Hospital Mortality; SARS-CoV-2; Risk Factors; Incidence; Adult; Hospitalization; Pneumonia, Viral
PubMed: 38797852
DOI: 10.1186/s12890-024-03071-0 -
Vaccines May 2024Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including...
Adenoviruses are efficient and safe vectors for delivering target antigens and adenovirus-based vaccines have been used against a wide variety of pathogens, including tuberculosis and COVID-19. Cost-effective and scalable biomanufacturing processes are critical for the commercialization of adenovirus-vectored vaccines. Adenoviral vectors are commonly produced through the infection of batch cultures at low cell density cultures, mostly because infections at high cell densities result in reduced cell-specific virus productivity and does not improve volumetric productivity. In this study, we have investigated the feasibility of improving the volumetric productivity by infecting fed-batch cultures at high cell densities. Four commercial and one in-house developed serum-free media were first tested for supporting growth of HEK 293 cells and production of adenovirus type 5 (Ad5) in batch culture. Two best media were then selected for development of fed-batch culture to improve cell growth and virus productivity. A maximum viable cell density up to 16 × 10 cells/mL was achieved in shake flask fed-batch cultures using the selected media and commercial or in-house developed feeds. The volumetric virus productivity was improved by up to six folds, reaching 3.0 × 10 total viral particles/mL in the fed-batch culture cultivated with the media and feeds developed in house and infected at a cell density of 5 × 10 cells/mL. Additional rounds of optimization of media and feed were required to maintain the improved titer when the fed-batch culture was scaled up in a bench scale (3 L) bioreactor. Overall, the results suggested that fed-batch culture is a simple and feasible process to significantly improve the volumetric productivity of Ad5 through optimization and balance of nutrients in culture media and feeds.
PubMed: 38793775
DOI: 10.3390/vaccines12050524 -
Viruses May 2024An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections...
BACKGROUND AND AIMS
An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections have been suggested as possible triggers. However, the potential etiology is still unclear. We aimed to characterize a cohort of children with HUO in Israel in view of the COVID-19 pandemic.
METHOD
Demographics, clinical data, and laboratory results on the children compatible with the CDC criteria for HUO were collected by the established registry of the Ministry of Health. Available specimens were sent to the Central Virology Laboratory.
RESULTS
A total of 39 children were included in the registry. A total of 20 were enrolled prospectively, in which human herpes virus 6 (HHV6) infection or reactivation was identified in 11/19, adenovirus was found in 4/19 of the cases, and AAV2 was detected in 2/16. Past COVID-19 exposure was recorded for 24/39 of the children. A total of 10 children underwent liver biopsy, and 8 were successfully treated with steroids and 2 underwent liver transplantation.
CONCLUSIONS
The COVID-19 pandemic and the related containment measures combined with reactivation or active infection with other viruses could have been a trigger for the HUO outbreak. In our cohort, HHV6 was the most abundant finding.
Topics: Humans; COVID-19; Child; Female; Male; Child, Preschool; Infant; Israel; SARS-CoV-2; Adolescent; Herpesvirus 6, Human; Disease Outbreaks; Prospective Studies; Acute Disease; Pandemics
PubMed: 38793689
DOI: 10.3390/v16050808 -
Viruses May 2024Numerous human adenovirus (AdV) types are endowed with arginine-glycine-aspartic acid (RGD) sequences that enable them to recognize vitronectin-binding (αv) integrins.... (Review)
Review
Numerous human adenovirus (AdV) types are endowed with arginine-glycine-aspartic acid (RGD) sequences that enable them to recognize vitronectin-binding (αv) integrins. These RGD-binding cell receptors mediate AdV entry into host cells, a crucial early step in virus infection. Integrin interactions with adenoviruses not only initiate receptor-mediated endocytosis but also facilitate AdV capsid disassembly, a prerequisite for membrane penetration by AdV protein VI. This review discusses fundamental aspects of AdV-host interactions mediated by integrins. Recent efforts to re-engineer AdV vectors and non-viral nanoparticles to target αv integrins for bioimaging and the eradication of cancer cells will also be discussed.
Topics: Humans; Genetic Therapy; Integrins; Virus Internalization; Genetic Vectors; Adenoviruses, Human; Adenoviridae; Animals; Receptors, Virus; Neoplasms; Integrin alphaV; Oligopeptides
PubMed: 38793651
DOI: 10.3390/v16050770 -
Viruses May 2024Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still...
Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation ( < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view.
Topics: Humans; Coinfection; Respiratory Tract Infections; Italy; Child, Preschool; Child; Infant; Female; Male; Tertiary Care Centers; COVID-19; SARS-CoV-2; Hospitals, Pediatric; Adolescent; Human bocavirus; Virus Diseases; Hospitalization; Viruses; Infant, Newborn; Metapneumovirus
PubMed: 38793631
DOI: 10.3390/v16050750 -
Frontiers in Immunology 2024Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection against the virus. While virus neutralization is a key function of...
INTRODUCTION
Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection against the virus. While virus neutralization is a key function of spike-specific antibodies, antibodies also mediate Fc-dependent activities that can play a role in protection or pathogenesis.
METHODS
This study characterized serum antibody responses elicited after two doses of heterologous adenovirus-vectored (Ad26/ Ad5) vaccines.
RESULTS
Vaccine-induced antibody binding titers and Fc-mediated functions decreased over six months, while neutralization titers remained stable. Comparison of antibody isotypes elicited after Ad26/Ad5 vs. LNP-mRNA vaccination and after infection showed that anti-spike IgG1 were dominant and produced to high levels in all groups. The Ad26/Ad5 vaccines also induced IgG4 but not IgG2 and IgG3, whereas the LNP-mRNA vaccines elicited a full Ig spectrum (IgM, IgG1-4, IgA1-2). Convalescent COVID-19 patients had mainly IgM and IgA1 alongside IgG1. Despite these differences, the neutralization potencies against early variants were similar. However, both vaccine groups had antibodies with greater Fc potencies of binding complement and Fcg receptors than the COVID-19 group. The Ad26/Ad5 group also displayed a greater potency of RBD-specific antibody-mediated cellular phagocytosis.
DISCUSSION
Antibodies with distinctive quality were induced by different vaccines and infection. The data imply the utility of different vaccine platforms to elicit antibody responses with fine-tuned Fc activities.
Topics: Humans; SARS-CoV-2; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus; Female; Immunoglobulin G; Antibodies, Neutralizing; Male; Immunoglobulin Fc Fragments; Ad26COVS1; Adult; Middle Aged; Adenoviridae; Genetic Vectors; Immunoglobulin A
PubMed: 38779671
DOI: 10.3389/fimmu.2024.1382619 -
Journal of Hematology & Oncology May 2024Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low...
Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with Epstein‒Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Female; Programmed Cell Death 1 Receptor; Immune Checkpoint Inhibitors; Antibodies, Monoclonal, Humanized; Immunotherapy; Middle Aged; Transplantation, Homologous; Adenoviridae Infections; Adenovirus Infections, Human; Lymphoma, Large B-Cell, Diffuse
PubMed: 38764055
DOI: 10.1186/s13045-024-01557-2