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.

Case-control study of the epidemiological and clinical features of human adenovirus 55 and human adenovirus 7 infection in children with acute lower respiratory tract infections in Beijing, China, 2008-2013.

BACKGROUND: In adults, the emerging human adenovirus (HAdV) type 55 (HAdV-55) has been reported to cause more severe cases of adenovirus induced acute lower respiratory tract infections (ALRTIs) compared to other HAdV serotypes (HAdV-3, HAdV-7, HAdV-14). However, there is a dearth of comparative studies in children that address differences in the clinical epidemiological features between HAdV-55 and other HAdV serotypes that can also induce severe infection (such as HAdV-7). METHODS: We conducted a retrospective review of pediatric patients hospitalized at Beijing Children's Hospital with ALRTI from April 2008 to December 2013 who had adenovirus detected from nasopharyngeal or throat samples by PCR. We further compared pediatric patients infected with HAdV-55 to those infected with HAdV-7 using a case-control methodology by matching each subject with HAdV-55 infection to 4 patients with HAdV-7 infection within 2 months of each HAdV-55 infection. Demographic, clinical, and etiological data were collected and analyzed. RESULTS: Over the five-year period, HAdV was detected in 194 children. Of these, 8 were HAdV-55 positive. Epidemiological results showed that HAdV-55 infection was observed only in 4% of adenovirus infected children whereas HAdV-7 infection proportioned 53%. Most cases of HAdV-55 infection were identified during March and April, whereas HAdV-7 infection occurred throughout the year. Wheezing was significantly less frequent in the HAdV-55 group. No patients infected with HAdV-55 presented with vomiting or had any underlying disease. Coinfections with other respiratory tract pathogens were frequent among children infected with either HAdV-55 or HAdV-7. CONCLUSIONS: HAdV-55 circulated in Beijing during spring and appeared to cause pediatric respiratory infections that were as severe as HAdV-7 infections. Broader surveillance studies are needed.

A humanized anti-human adenovirus 55 monoclonal antibody with good neutralization ability.

Background: Human adenovirus type 55 (HAdV55) has a re-emerged as pathogen causing an acute respiratory disease presenting as a severe lower respiratory illness that can cause death. To date, there is no HAdV55 vaccine or treatment available for general use. Methods: Herein, a monoclonal antibody specific for HAdV55, mAb 9-8, was isolated from an scFv-phage display library derived from mice immunized with the purified inactived-HAdV55 virions. By using ELISA and a virus micro-neutralization assay, we evaluated the binding and neutralizing activity of mAb 9-8 following humanization. Western blotting analysis and antigen-antibody molecular docking analysis were used to identify the antigenic epitopes that the humanized monoclonal antibody 9-8-h2 recognized. After that, their thermal stability was determined. Results: MAb 9-8 showed potent neutralization activity against HAdV55. After humanization, the humanized neutralizing monoclonal antibody (9-8-h2) was identified to neutralize HAdV55 infection with an IC50 of 0.6050 nM. The mAb 9-8-h2 recognized HAdV55 and HAdV7 virus particles, but not HAdV4 particles. Although mAb 9-8-h2 could recognize HAdV7, it could not neutralize HAdV7. Furthermore, mAb 9-8-h2 recognized a conformational neutralization epitope of the fiber protein and the crucial amino acid residues (Arg 288, Asp 157, and Asn 200) were identified. MAb 9-8-h2 also showed favorable general physicochemical properties, including good thermostability and pH stability. Conclusions: Overall, mAb 9-8-h2 might be a promising molecule for the prevention and treatment of HAdV55.

Comparative analyses of clinical features reveal the severity of human adenovirus type 55 and type 7 in acute respiratory tract infections.

Introduction. Human adenovirus (HAdV) is an important pathogen in acute respiratory tract infections (ARTIs) and HAdV genotypes are associated with disease severity.Hypothesis. Comparative analyses of clinical features could reveal the severity of different HAdV genotypes in ARTIs.Aim. This study aimed to investigate the molecular epidemiology of HAdV infections and explore the correlations between clinical features and HAdV genotypes.Methodology. A retrospective study was conducted on ARTIs at Beijing Chao-Yang Hospital during the period 2011-2016. A standardized data form was used to record the clinical information. HAdV was detected by FQ-PCR from respiratory specimens, and genotypes were determined by entire hexon gene sequencing.Results. A total of 8044 samples were collected, of which 296 (3.7 %) were HAdV-positive. Patients ≤44 years old were more likely to be positive for HAdV. There were three peak periods of adenoviral infections, with detection rates of 13.03, 9.39 and 10.38 %, respectively. Six HAdV genotypes (HAdV-55, -7, -3, -14, -50, -2) were identified, with HAdV-55 and HAdV-7 being the most prevalent (50.6 and 21.5 %). Compared with HAdV-7 and other types, patients infected with HAdV-55 had a longer duration of fever (P=0.0428). Infections with HAdV-55 and HAdV-7 were more severe compared to those caused by other types, with higher rates of oxygen therapy and mechanical ventilation (P=0.0172 and P=0.0144). All five deaths were caused by HAdV-55.Conclusion. This study describes the epidemiological characteristics of HAdV infections in North China, revealing the higher severity of HAdV-55 and HAdV-7 in ARTIs. Thus, strengthened surveillance of HAdV genotypes is warranted.

Cross-infection of adenovirus among medical staff: A warning from the intensive care unit in a tertiary care teaching hospital in China.

RATIONALE: In 2019, a small HAdV55-associated outbreak of adenovirus infection occurred among the intensive care unit (ICU) staff in Xiangya Hospital of Central South University in Hunan Province, China, during the treatment of a patient. OBJECTIVE: To investigate the characteristics of a nosocomial adenovirus outbreak in an ICU. METHODS: We evaluated all the patients treated and the medical staff working in the ICU from August 1 to September 4, 2019. We further performed an epidemiological and molecular analysis for this outbreak from patient to healthcare workers and between healthcare workers. After the outbreak, we adopted exposure prevention and droplet prevention measures based on standard precautions. MEASUREMENTS AND MAIN RESULTS: Between August 1 and August 27, 2019, 27 cases of human adenovirus cross-infection were reported in our institution. Among the cases, eleven were doctors (41%), eleven were nurses (41%), three were respiratory therapists (11%), and two were caregivers (7%). The attack rate was 28.4%, and the fatality rate was 0. The results showed that contact with the index case, lack of hand hygiene or gloving adherence were risk factors for infection after adenovirus exposure. After taking specific precautions, no new cases of infection have appeared since August 27. CONCLUSIONS: Our results show that HAdV55 in a single patient had strong transmission potential in an intensive care unit with adequate facilities and standardized operation. We provide convincing evidence indicating that attention could be highlighted on the role of standard and specific precautions for controlling the spread of adenovirus in ICUs.

A recombinant trivalent vaccine candidate against human adenovirus types 3, 7, and 55.

Human adenoviruses types 3 (HAdV-3), 7 (HAdV-7) and 55 (HAdV-55) are major pathogens of acute respiratory infections (ARI) in children and adults. More than one type of HAdV can infect patients simultaneously, and the infections are sometimes fatal. However, there is currently no vaccine approved for general use in children and adults. Thus, development of a multivalent HAdV vaccine to combat HAdV infection becomes imperative. In this study, we constructed a new recombinant trivalent human adenovirus vaccine (rAdMHE3-h55), which expresses the hexon protein of HAdV-55 in the E3 region of rAdMHE3, a previously prepared bivalent vaccine candidate against HAdV-3 and HAdV-7. The results of in vitro neutralization assays indicate that rAdMHE3-h55 can induce the production of neutralizing antibodies against HAdV-3, HAdV-7, and HAdV-55 in mice. Furthermore, immunization with the recombinant trivalent vaccine candidate completely protected the mice challenged with HAdV-3, HAdV-7, orHAdV-55, respectively, showing lower lung viral loads and less lung Pathological changes was compared with those in unvaccinated mice. The current findings contribute to the development of a new adenovirus vaccine candidate and also advance this construction method for the generation of recombinant adenovirus vaccines. In conclusion, our recombinant trivalent vaccine rAdMHE3-h55 can provides protection against challenge with HAdV-3, HAdV-7, or HAdV-55 in mice. Future work of optimizing this vaccine candidate may lead to a more effective way of preventing respiratory diseases caused by common human adenoviruses.