A rapid and highly sensitive multiple detection of human adenovirus type 3, type 7 and respiratory syncytial virus by recombinase-aided reverse transcription PCR.

BACKGROUND: Polymerase chain reaction (PCR) has been widely used for many pathogen detection. However, PCR technology still suffers from long detection time and insufficient sensitivity. Recombinase-aided amplification (RAA) is a powerful nucleic acid detection tool with high sensitivity and amplification efficiency, but its complex probes and inability of multiplex detection hinder the further application of this technology. METHODS: In this study, we developed and validated the multiplex reverse transcription recombinase-aided PCR (multiplex RT-RAP) assay for human adenovirus 3 (HADV3), human adenovirus 7 (HADV7), and human respiratory syncytial virus (HRSV) within 1 h with Human RNaseP protein as a reference gene to monitor the whole process. RESULTS: Using recombinant plasmids, the sensitivity of multiplex RT-RAP for the detection of HADV3, HADV7, and HRSV was 18, 3, and 18 copies per reaction, respectively. The multiplex RT-RAP showed no cross-reactivity with other respiratory viruses, demonstrating its good specificity. A total of 252 clinical specimens were tested by multiplex RT-RAP and the results were found to be consistent with those of corresponding RT-qPCR assays. After testing serial dilutions of selected positive specimens, the detection sensitivity of multiplex RT-RAP was two to eightfold higher than that of corresponding RT-qPCR. CONCLUSION: We conclude the multiplex RT-RAP is a robust, rapid, highly sensitive, and specific assay with the potential to be used in the screening of clinical samples with low viral load.

Human Adenovirus Type 26 Infection Mediated by αvß3 Integrin Is Caveolin-1-Dependent.

Human adenovirus type 26 (HAdV26) has been recognized as a promising platform for vaccine vector development, and very recently vaccine against COVID-19 based on HAdV26 was authorized for emergency use. Nevertheless, basic biology of this virus, namely, pathway which HAdV26 uses to enter the cell, is still insufficiently known. We have shown here that HAdV26 infection of human epithelial cells expressing low amount of αvß3 integrin involves clathrin and is caveolin-1-independent, while HAdV26 infection of cells with high amount of αvß3 integrin does not involve clathrin but is caveolin-1-dependent. Thus, this study demonstrates that caveolin-1 is limiting factor in αvß3 integrin-mediated HAdV26 infection. Regardless of αvß3 integrin expression, HAdV26 infection involves dynamin-2. Our data provide for the first-time description of HAdV26 cell entry pathway, hence increase our knowledge of HAdV26 infection. Knowing that functionality of adenovirus vector is influenced by its cell entry pathway and intracellular trafficking, our results will contribute to better understanding of HAdV26 immunogenicity and antigen presentation when used as vaccine vector. IMPORTANCE In order to fulfill its role as a vector, adenovirus needs to successfully deliver its DNA genome to the host nucleus, a process highly influenced by adenovirus intracellular translocation. Thus, cell entry pathway and intracellular trafficking determine functionality of human adenovirus-based vectors. Endocytosis of HAdV26, currently extensively studied as a vaccine vector, has not been described so far. We present here that HAdV26 infection of human epithelial cells with high expression of αvß3 integrin, one of the putative HAdV26 receptors, is caveolin-1- and partially dynamin-2-dependent. Since caveolin containing domains provide a unique environment for specific signaling events and participate in inflammatory signaling one can imagine that directing HAdV26 cell entry toward caveolin-1-mediate pathway might play role in immunogenicity of this virus. Therefore, our results contribute to better understanding of HAdV26 infection pathway, hence, can be helpful in explaining induction of immune response and antigen presentation by HAdV26-based vaccine vector.

Recombinant human adenovirus type 5 based vaccine candidates against GIIa- and GIIb-genotype porcine epidemic diarrhea virus induce robust humoral and cellular response in mice.

Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus causing severe watery diarrhea, vomiting, dehydration, and death in piglets. However, most commercial vaccines are developed based on the GI genotype strains, and have poor immune protection against the currently dominant GII genotype strains. Therefore, four novel replication-deficient human adenovirus 5-vectored vaccines expressing codon-optimized forms of the GIIa and GIIb strain spike and S1 glycoproteins were constructed, and their immunogenicity was evaluated in mice by intramuscular (IM) injection. All the recombinant adenoviruses generated robust immune responses, and the immunogenicity of recombinant adenoviruses against the GIIa strain was stronger than that of recombinant adenoviruses against the GIIb strain. Moreover, Ad-XT-tPA-Sopt-vaccinated mice elicited optimal immune effects. In contrast, mice immunized with Ad-XT-tPA-Sopt by oral gavage did not induce strong immune responses. Overall, IM administration of Ad-XT-tPA-Sopt is a promising strategy against PEDV, and this study provides useful information for developing viral vector-based vaccines.

Apobec3A Deamination Functions Are Involved in Antagonizing Efficient Human Adenovirus Replication and Gene Expression.

Apobec3A is involved in the antiviral host defense, targeting nuclear DNA, introducing point mutations, and thereby activating DNA damage response (DDR). Here, we found a significant upregulation of Apobec3A during HAdV infection, including Apobec3A protein stabilization mediated by the viral proteins E1B-55K and E4orf6, which subsequently limited HAdV replication and most likely involved a deaminase-dependent mechanism. The transient silencing of Apobec3A enhanced adenoviral replication. HAdV triggered Apobec3A dimer formation and enhanced activity to repress the virus. Apobec3A decreased E2A SUMOylation and interfered with viral replication centers. A comparative sequence analysis revealed that HAdV types A, C, and F may have evolved a strategy to escape Apobec3A-mediated deamination via reduced frequencies of TC dinucleotides within the viral genome. Although viral components induce major changes within infected cells to support lytic life cycles, our findings demonstrate that host Apobec3A-mediated restriction limits virus replication, albeit that HAdV may have evolved to escape this restriction. This allows for novel insights into the HAdV/host-cell interplay, which broaden the current view of how a host cell can limit HAdV infection. IMPORTANCE Our data provide a novel conceptual insight into the virus/host-cell interplay, changing the current view of how a host-cell can defeat a virus infection. Thus, our study reveals a novel and general impact of cellular Apobec3A on the intervention of human adenovirus (HAdV) gene expression and replication by improving the host antiviral defense mechanisms, thereby providing a novel basis for innovative antiviral strategies in future therapeutic settings. Ongoing investigations of the cellular pathways that are modulated by HAdV are of great interest, particularly since adenovirus-based vectors actually serve as COVID vaccine vectors and also frequently serve as tools in human gene therapy and oncolytic treatment options. HAdV constitute an ideal model system by which to analyze the transforming capabilities of DNA tumor viruses as well as the underlying molecular principles of virus-induced and cellular tumorigenesis.

An Old Acquaintance: Could Adenoviruses Be Our Next Pandemic Threat?

Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 110 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, are stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. This review aimed to highlight the HAdV variability and the pandemic potential that a HAdV3 and 7 recombinant could have considering the aggressive outbreaks produced in health facilities. Herein, we described the characteristics of HAdV, from the infection to treatment, vaccine development, and the evaluation of the social determinants of health associated with HAdV, suggesting the necessary measures for future sanitary control to prevent disasters such as the SARS-CoV-2 pandemic, with an emphasis on the use of recombinant AdV vaccines to control other potential pandemics.

Human adenovirus lung disease: outbreaks, models of immune-response-driven acute lung injury and pandemic potential.

PURPOSE OF REVIEW: An overview of epidemic, human adenovirus (HAdV) lung infections with proposed studies of the viral/host immune response interface to better understand mechanisms of immunopathogenesis, for development of improved responses to a potential HAdV pandemic. RECENT FINDINGS: Emergent HAdV strains 7, 3, 4, 14 are the most common types associated with infection outbreaks. Recent outbreaks have revealed increased community spread, beyond epidemic group settings. The ongoing circulation of these virulent HAdV strains might allow for further HAdV adaptation, with increased HAdV spread and disease severity in the population that could theoretically result in expansion to a pandemic level. SUMMARY: Public health screening has revealed spread of HAdV outbreak strains to the general community. Despite expanded awareness of viral respiratory diseases during the SARS-CoV-2 pandemic, there has been limited, systematic monitoring of HAdV infection in the population. The shift in clinical laboratories to a focus on molecular diagnostics and away from classical methods of viral characterization has reduced the distribution of outbreak HAdV strains to the research community to study mechanisms of pathogenesis. This change risks reduced development of new preventive and therapeutic strategies that could be needed in the event of more widespread HAdV epidemics.

Measurement of Adenovirus-Based Vector Heterogeneity.

Adenovirus vectors have become an important class of vaccines with the recent approval of Ebola and COVID-19 products. In-process quality attribute data collected during Adenovirus vector manufacturing has focused on particle concentration and infectivity ratios (based on viral genome: cell-based infectivity), and data suggest only a fraction of viral particles present in the final vaccine product are efficacious. To better understand this product heterogeneity, lab-scale preparations of two Adenovirus viral vectors, (Chimpanzee adenovirus (ChAdOx1) and Human adenovirus Type 5 (Ad5), were studied using transmission electron microscopy (TEM). Different adenovirus morphologies were characterized, and the proportion of empty and full viral particles were quantified. These proportions showed a qualitative correlation with the sample's infectivity values. Liquid chromatography-mass spectrometry (LC-MS) peptide mapping was used to identify key adenovirus proteins involved in viral maturation. Using peptide abundance analysis, a ∼5-fold change in L1 52/55k abundance was observed between low-(empty) and high-density (full) fractions taken from CsCl ultracentrifugation preparations of ChAdOx1 virus. The L1 52/55k viral protein is associated with DNA packaging and is cleaved during viral maturation, so it may be a marker for infective particles. TEM and LC-MS peptide mapping are promising higher-resolution analytical characterization tools to help differentiate between relative proportions of empty, non-infectious, and infectious viral particles as part of Adenovirus vector in-process monitoring, and these results are an encouraging initial step to better differentiate between the different product-related impurities.

The clinical and virological features of two children's coinfections with human adenovirus type 7 and human coronavirus-229E virus.

Objective: Human adenovirus (HAdV) coinfection with other respiratory viruses is common, but adenovirus infection combined with human coronavirus-229E (HCoV-229E) is very rare. Study design and setting: Clinical manifestations, laboratory examinations, and disease severity were compared between three groups: one coinfected with HAdV-Ad7 and HCoV-229E, one infected only with adenovirus (mono-adenovirus), and one infected only with HCoV-229E (mono-HCoV-229E). Results: From July to August 2019, there were 24 hospitalized children: two were coinfected with HAdV-Ad7 and HCoV-229E, and 21 were infected with a single adenovirus infection. Finally, one 14-year-old boy presented with a high fever, but tested negative for HAdV-Ad7 and HCoV-229E. Additionally, three adult asymptotic cases with HCoV-229E were screened. No significant difference in age was found in the coinfection and mono-adenovirus groups (11 vs. 8 years, p = 0.332). Both groups had the same incubation period (2.5 vs. 3 days, p = 0.8302), fever duration (2.5 vs. 2.9 days, p = 0.5062), and length of hospital stay (7 vs. 6.76 days, p = 0.640). No obvious differences were found in viral loads between the coinfection and mono-adenovirus groups (25.4 vs. 23.7, p = 0.570), or in the coinfection and mono-HCoV-229E groups (32.9 vs. 30.06, p = 0.067). All cases recovered and were discharged from the hospital. Conclusion: HAdV-Ad7 and HCoV-229E coinfection in healthy children may not increase the clinical severity or prolong the clinical course. The specific interaction mechanism between the viruses requires further study.

The changed endemic pattern of human adenovirus from species B to C among pediatric patients under the pressure of non-pharmaceutical interventions against COVID-19 in Beijing, China.

BACKGROUND: Under the pressure of non-pharmaceutical interventions (NPIs) targeting severe acute respiratory syndrome coronavirus 2, the prevalence of human adenovirus (HAdV) was monitored before and after NPIs launched on Jan 24, 2020 in pediatric patients in Beijing, China. METHODS: Respiratory samples collected from children hospitalized with acute respiratory infections from Jan 2015 to Dec 2021 were screened by direct immunofluorescence test or capillary electrophoresis-based multiplex PCR assay. The hexon, penton base, and fiber genes were amplified from HAdV positive specimens, then sequenced. For HAdV typing, phylogenetic trees were built by MEGA X. Then clinical data of HAdV positive cases were collected. All data were evaluated using SPSS Statistics 22.0 software. RESULTS: A total of 16,097 children were enrolled and 466 (2.89%, 466/16,097) were HAdV-positive. The positive rates of HAdV varied, ranging from 4.39% (151/3,438) in 2018 to1.25% (26/2,081) in 2021, dropped from 3.19% (428/13,408) to 1.41% (38/2,689) from before to after NPIs launched (P < 0.001). There were 350 cases typed into nine types of species B, C, or E and 34 recorded as undetermined. Among them, HAdV-B3 (51.56%, 198/384) was the most prevalent types from 2015 to 2017, and HAdV-B7 (29.17%, 112/384) co-circulated with HAdV-B3 from 2018 to 2019. After NPIs launched, HAdV-B3 and B7 decreased sharply with HAdV-B7 undetected in 2021, while HAdV-C1 became the dominant one and the undetermined were more. CONCLUSIONS: The endemic pattern of HAdV changed in Beijing because of the NPIs launched for COVID-19. Especially, the dominant types changed from HAdV-B to HAdV-C.

Acute hepatitis of unknown aetiology among children around the world.

By 26 August 2022, the number of cases of acute hepatitis of unknown etiology (AHUA) has drastically increased to 1115 distributed in 35 countries that fulfill the World Health Organization definition. Several hypotheses on the cause of AHUA have been proposed and are being investigated around the world. In the recent United Kingdom (UK) report, human adenovirus (HAdV) with adeno-associated virus (AAV) co-infection is the leading hypothesis. However, there is still limited evidence in establishing the causal relationship between AHUA and any potential aetiology. The leading aetiology continues to be HAdV infection. It is reported that HAdV genomics is not unusual among the population in the UK, especially among AUHA cases. Expanding the surveillance of HAdV and AAV in the population and the environment in the countries with AUHA cases is suggested to be the primary action. Metagenomics should be used in detecting other infectious pathogens on a larger scale, to supplement the detection of viruses in the blood, stool, and liver specimens from AUHA cases. It is useful to develop a consensus-specific case definition of AHUA to better understand the characteristics of these cases globally based on all the collected cases.

Analysis of the Prevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Student Cohorts Reveals Low-Prevalence Types and a Decline in Binding Antibody Levels during the SARS-CoV-2 Pandemic.

Human adenoviruses (HAdVs) are important tools for vector development for applications such as immunization, oncolytic therapy, or gene therapy. However, their potential is limited by preexisting immunity against HAdV; therefore, it is important for future vector design to identify HAdV types of low seroprevalence. To provide such data, we performed an analysis of both binding and neutralizing antibodies in sera from three student cohorts. Among these young adults, we found the highest levels of binding antibodies against HAdV-C1, -D33, -A31, -B35, -C5, -D26, -E4, and -B7. The highest levels of neutralizing antibodies were detected against HAdV-C2, -B3, -C1, -F41, -G52, -C5, -A31, -E4, and -C6. While binding and neutralizing antibody levels were not different in males and females or in samples collected before and after the cold season, we found significantly lower levels of binding antibodies in sera collected 20 months after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, indicating a waning of HAdV-specific antibody responses on that time scale. Our data indicate that mainly HAdV types of species A, B, and D show low seroprevalence with regard to both binding and neutralizing antibodies and may represent good candidates for further characterization and future development as novel vector systems. IMPORTANCE Vectors based on human adenoviruses (HAdVs) are important for the development of novel immunizations, oncolytic therapies, and gene therapies. The use of HAdV-based vaccines against Ebola virus, the rapid adaptation of the vector technology for vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their very good efficacy have shown the great potential of HAdV-based vaccines. Preexisting immunity against HAdV-based vectors can limit their efficacy significantly; therefore, it is highly desirable to identify HAdV types with low seroprevalence. The identification of new suitable HAdV types for vector development will broaden the repertoire and contribute to future epidemic preparedness.

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

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

Deep sequencing analysis of clinical samples from patients with acute infectious conjunctivitis during the COVID-19 delta surge in Madurai, India.

BACKGROUND: Seasonal outbreaks of infectious conjunctivitis remain a public health issue. Determination of outbreak etiologies in the context of a worldwide pandemic may provide useful information to guide public health strategies. The aim of this study was to identify pathogens associated with outpatient infectious conjunctivitis during the COVID-19 Delta surge. METHODS: This prospective study was conducted from April 2021 to September 2021. All outpatients presenting to the Aravind Eye Center (Madurai, India) with signs and symptoms consistent with acute infectious conjunctivitis were eligible. Three swabs were obtained from each participant: one from each conjunctiva and one from the anterior nares. Samples were processed for metagenomic RNA deep sequencing (RNA-seq). RESULTS: Samples from 106 study participants were sequenced. The most common presenting symptoms were tearing (86%) and itching (71%). Preauricular lymphadenopathy was present in 38% of participants. 20% of participants had close contacts with similar symptoms. Systemic symptoms such as coughing, runny nose, vomiting or diarrhea were uncommonly reported. 60% of all participants used some medicated eye drops upon enrollment. 75% of study participants demonstrated infection with human adenovirus D (HAdV-D). 11% of conjunctivitis was associated with SARS-CoV-2. 15% had no definitive pathogen detected. 8% of all participants had codetection of more than one pathogen on RNA-seq. CONCLUSIONS: During the COVID-19 Delta surge in India, HAdV-D was the most common pathogen associated with infectious conjunctivitis. SARS-CoV-2 was the second most common associated pathogen. Seasonal surveillance may be necessary for the determination of emerging and reemerging pathogens responsible for infectious conjunctivitis.

A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

Clinical features, treatment and outcomes of an outbreak of type 7 adenovirus pneumonia in centralized residence young adults.

BACKGROUND: Human adenovirus type B7 (HAdV-B7) has been reported to cause pneumonia. However, there are limited data about the epidemiological and clinical features of HAdV-B7 pneumonia in young adults. METHODS: This retrospective observational study included 52 patients diagnosed of human adenovirus B7 pneumonia in Nanjing, China from February 7, 2016, to February 20, 2016. We retrospectively collected and analyzed clinical, laboratory, and radiologic features, treatments and outcomes. RESULTS: The median age of the 52 patients was 19.5 years (IQR 18.0-21.0). The most common symptoms were fever (50, 96.2%), cough (49, 94.2%), and expectoration (48, 92.3%). Most of the routine hematology and blood chemistry parameters were within the normal range. The predominant abnormal patterns seen on chest CT were unilateral (33, 66%), multifocal (36, 72%), and ground-glass opacity (27, 54%), mainly involving the left lower lobes (41 [36.0%] of 114 affected segments). As the disease progressed in the second week after symptom onset, consolidation and mixed patterns became more common, while the ground glass opacity pattern decreased. The single-agent ribavirin therapy group had a significantly shorter duration of nonrespiratory symptoms, and no statistically significant difference was observed between the single-agent methylprednisolone group and the nonglucocorticoid group. CONCLUSIONS: The main symptoms in immunocompetent patients with adenovirus type 7 are fever, cough and sputum, with no significant abnormalities in laboratory tests. Chest CT scan mostly shows a ground-glass opacity at the beginning of the disease, which subsequently changes to a mixed pattern. Ribavirin and glucocorticoids did not shorten the course of disease.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

Editorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic.

The range of long-term clinical conditions following SARS-CoV-2 infection in adults is now recognized. However, the prevalence, presentation, and risk factors for long COVID, or post-COVID-19, in children are less well understood because there have been few follow-up studies or long-term clinical trials in children with COVID-19. However, recent studies have shown that children with mild or asymptomatic COVID-19 may develop long-term sequelae that include cough, fatigue, and lethargy. The incidence and severity of common childhood respiratory viruses have changed in the past year, including respiratory syncytial virus (RSV). Hepatitis of unknown cause in children with SARS-CoV-2 infection is increasingly reported. Although both a viral cause and an autoimmune cause have been proposed, adenovirus type 41 infection is of current interest. These findings support immunization programs for SARS-CoV-2 in children, and infection surveillance and monitoring of the changing patterns and severity of other pediatric viral infections, including adenovirus type 41 and RSV, to develop and administer effective vaccines. This Editorial aims to highlight what is currently known of the long-term effects of symptomatic and asymptomatic SARS-CoV-2 infection in children and the changing epidemiology and pathogenesis of previously common childhood viral infections now driven by the COVID-19 pandemic.

Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study.

BACKGROUND: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. METHODS: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. RESULTS: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. CONCLUSION: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.