Temporal maturation of neutralizing antibodies in COVID-19 convalescent individuals improves potency and breadth to circulating SARS-CoV-2 variants.

Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1-10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.

Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.

Characterization of a new SARS-CoV-2 variant that emerged in Brazil.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.

Effects of treatment with corticosteroids on human rhinovirus-induced asthma exacerbations in pediatric inpatients: a prospective observational study.

BACKGROUND: Human rhinoviruses (HRVs) infection is a common cause of exacerbations in pediatric patients with asthma. However, the effects of corticosteroids on HRV-induced exacerbations in pediatric asthma are unknown. We conducted a prospective observational study to determine the viral pathogens in school-age pediatric inpatients with asthma exacerbations. We assessed the effects of maintenance inhaled corticosteroids (ICS) on the detection rates of HRV species and treatment periods of systemic corticosteroids during exacerbations on pulmonary lung function after exacerbations. METHODS: Nasopharyngeal samples and clinical information were collected from 59 patients with asthma exacerbations between April 2018 and March 2020. Pulmonary function tests were carried out 3 months after exacerbations in 18 HRV-positive patients. Changes in forced expiratory volume in 1 second (FEV1)% predicted from baseline in a stable state were compared according to the treatment periods of systemic corticosteroids. RESULTS: Fifty-four samples collected from hospitalized patients were analyzed, and viral pathogens were identified in 45 patients (83.3%) using multiplex PCR assay. HRV-A, -B, and -C were detected in 16 (29.6%), one (1.9%), and 16 (29.6%) patients, respectively. The detection rates of HRV-C were lower in the ICS-treated group compared with those in the ICS-untreated group (p = 0.01), whereas maintenance ICS treatment did not affect the detection rate for viral pathogens in total and HRV-A. Changes in FEV1% predicted in patients treated with systemic corticosteroids for 6-8 days (n = 10; median, 4.90%) were higher than those in patients treated for 3-5 days (n = 8; median, - 10.25%) (p = 0.0085). CONCLUSIONS: Maintenance ICS reduced the detection rates of HRV (mainly HRV-C) in school-age inpatients with asthma exacerbations, and the treatment periods of systemic corticosteroids during exacerbations affected lung function after HRV-induced exacerbations. The protective effects of corticosteroids on virus-induced asthma exacerbations may be dependent upon the types of viral pathogen.

Two Cases of Breakthrough Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections Caused by the Omicron Variant (B.1.1.529 Lineage) in International Travelers to Japan.

In November 2021, the World Health Organization designated a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern, Omicron (PANGO lineage B.1.1.529). We report on the first 2 cases of breakthrough coronavirus disease 2019 (COVID-19) caused by Omicron in Japan among international travelers returning from the country with undetected infection. The spread of infection by Omicron were considered.

Duration of Infectious Virus Shedding by SARS-CoV-2 Omicron Variant-Infected Vaccinees.

To determine virus shedding duration, we examined clinical samples collected from the upper respiratory tracts of persons infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in Japan during November 29-December 18, 2021. Vaccinees with mild or asymptomatic infection shed infectious virus 6-9 days after onset or diagnosis, even after symptom resolution.

Useful manifestations to detect adenovirus in children with upper respiratory infections: A retrospective study.

OBJECTIVE: Approximately 1 million adenovirus immunochromatography (IC) kits are annually used in Japan. However, no practical strategies have been developed regarding their use for detecting adenovirus. The present study aims to verify the usefulness of clinical manifestations in making decisions regarding the use of adenovirus IC kits for children with upper respiratory infections (URI). METHODS: The medical records of 825 pediatric cases tested by IC kits for adenovirus were extracted from clinical laboratory department database over a 3-year period at our hospital. Among them, 585 patients were suspected adenovirus URI, and their clinical manifestations were reviewed. After data cleaning, 10 types of clinical manifestations were statistically analyzed between adenovirus IC kit-positive and -negative groups. Multivariate analysis was performed to select significant clinical manifestations using adenovirus IC kit positivity as the objective variable. RESULTS: Among 585 pediatric patients, the cases of 420 patients, with suitable data for whom no other pathogen was detected, were reviewed. Adenovirus was detected in 86 cases. Multivariate analysis identified a significant difference for three clinical manifestations: (1) fever ≥ 39.0°C, (2) rhinorrhea, and (3) tonsillar exudate. The negativity rate for the IC kit was 90% when none of the three manifestations was observed. CONCLUSIONS: The results suggested that IC kits for adenovirus tend to give negative results in cases that lack all the three above mentioned clinical manifestations.

Novel SARS-CoV-2 Variant in Travelers from Brazil to Japan.

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with higher transmission potential have been emerging globally, including SARS-CoV-2 variants from the United Kingdom and South Africa. We report 4 travelers from Brazil to Japan in January 2021 infected with a novel SARS-CoV-2 variant with an additional set of mutations.

Possible nosocomial transmission of virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.

A fatal case of acute encephalopathy in a child due to coxsackievirus A2 infection: a case report.

BACKGROUND: Certain types of enteroviruses, including coxsackieviruses, cause encephalitis, and other neurological complications. However, these pathogens rarely cause fatal infections, especially in immunocompetent infants. In this study, we present a rare case of acute encephalopathy caused by coxsackievirus A2 (CV-A2), which progressed rapidly in a previously healthy female child. CASE PRESENTATION: In June 2013, a 26-month-old female child from Kanagawa, Japan, was found unresponsive during sleep. She was healthy until that morning. Her temperature was 37 °C at 08:00. She was feeling fine and went to the nursery that same morning. However, her condition worsened around noon. Therefore, she went home and slept at around 13:00. Surprisingly, after 2 h, her parents checked on her and found that she was lying on her back and was not breathing. Hence, she was immediately taken to a hospital by ambulance, but she was declared dead on arrival at the hospital. Subsequently, pathological autopsy and pathogenetic analysis, including multiple pathogen detection real-time PCR, were conducted to investigate the cause of death. The examination results revealed that she had an infectious respiratory disease and acute encephalopathy due to a CV-A2 infection. CONCLUSIONS: Based on our findings, we concluded that a previously healthy girl who had no immediate history of underlying medical condition were susceptible to death by acute encephalopathy due to CV-A2 infections. We proposed this conclusion because the patient's condition progressed rapidly in less than 2 h and eventually led to her death. This is the first report on an acute encephalitis-dependent death in a child due to CV-A2 infection.

Detection of adenovirus hepatitis and acute liver failure in allogeneic hematopoietic stem cell transplant patients.

Human adenovirus (HAdV) is an important cause of the common cold and epidemic keratoconjunctivitis in immunocompetent individuals. In immunocompromised patients, HAdV can sometimes cause severe infection such as cystitis, gastroenteritis, pneumonia, encephalitis, hepatitis, or disseminated disease, resulting in significant morbidity and also mortality. In particular, severe cases have been reported in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Indeed HAdV has been recognized as a pathogen that requires careful monitoring in allo-HSCT patients. While HAdV hepatitis leading to severe acute liver failure is rare, such liver failure progresses rapidly and is often fatal. Unfortunately, HAdV hepatitis has few characteristic symptoms and physical findings, which makes it difficult to promptly confirm and start treatment. We report here four cases of HAdV hepatitis after allo-HSCT and their autopsy findings.

Human Adenovirus B7d-Associated Urethritis after Suspected Sexual Transmission, Japan.

Outbreaks of acute respiratory disease associated with human adenovirus (HAdV) B7d have been reported, including fatal cases in the United States. In 2018, we detected HAdV-B7d in a patient with urethritis, probably transmitted through sexual contact. Infectious HAdV-B7d was excreted in urine and gargle for >10 days after the disappearance of symptoms.

Evaluation of a silver-amplified immunochromatography kit for adenoviral conjunctivitis.

OBJECTIVE: To compare and evaluate the sensitivity of a newly developed silver-amplified immunochromatography (SAI) kit with various immunochromatography (IC) kits for adenoviruses based on the detection limit (copies/test). METHODS: An SAI kit and four ophthalmic IC kits were evaluated. The detection limits of the five kits were determined using the limiting dilution method for 15 conjunctivitis-associated adenoviruses (adenoviruses 1, 2, 3, 4, 5, 7, 8, 11, 37, 53, 54, 56, 64, 81, and 85). The detection limits were presented as numerical values as determined by real-time polymerase chain reaction (PCR). RESULTS: The detection limit of the SAI kit for the adenovirus types ranged from 1.0 × 103 -5.0 × 10 4 copies/test (geometric mean, 4.7 × 10 3 ). SAI had a 10-250-fold lower detection limit than the four IC kits for all adenoviruses studied. There were also differences in detection limits among the adenovirus types for each kit. DISCUSSION: The detection limit of the SAI kit was drastically reduced because the silver-amplification reaction increased the color development sensitivity. The results revealed the high sensitivity of SAI for detecting adenoviruses and suggested its usefulness for conjunctivitis examination.

Evaluation of adenovirus amplified detection of immunochromatographic test using tears including conjunctival exudate in patients with adenoviral keratoconjunctivitis.

BACKGROUND: We evaluated a novel silver amplification immunochromatography test for rapid detection of adenovirus (AdV) antigen equipped with an automated reader system using tears including conjunctival exudate in patients with adenoviral keratoconjunctivitis. METHODS: Two kinds of immunochromatographic (IC) kits, a conventional IC kit for conjunctival scrapings (control kit) and an IC kit using tears including conjunctival exudate collected by pressing a filter paper strip on the conjunctiva (test kit), were tested on 90 patients who attended Migita Eye Clinic with suspected adenoviral conjunctivitis. The results of the test kits were automatically obtained by a specific reader, which was based on silver amplification immunochromatography system, in 15 min. The detection of AdV was confirmed by real-time polymerase chain reaction (PCR) method, and typing was performed by direct sequencing. Comparative dilution assay was carried out with the two kits, using AdV type 3 and type 54 strains. RESULTS: The sensitivity of the control kit and test kit was 89.8% and 98.3%, respectively. The specificity of both kits was 100%. A significant difference in the sensitivities of the two IC kits against PCR positivity was observed (P < 0.01). A significant correlation was found between AdV DNA copy numbers on a logarithmic scale obtained with the two tests (P < 0.01). The sensitivity of the test kit was 32-64-fold higher than that of the control kit without silver amplification for both AdV types. CONCLUSIONS: These results suggest that this novel amplified AdV detection kit using tears including conjunctival exudate is useful, because it decreases patients' discomfort from specimen collection and its sensitivity is significantly higher than that of the conventional IC kit.

Human adenoviral type 54 keratoconjunctivitis accompanied by stellate keratitis and keratic precipitates: two cases.

BACKGROUND: Of the 10 patients with adenoviral type 54 keratoconjunctivitis examined at Nojima Hospital, 2 developed stellate keratitis and mutton-fat keratic precipitates (KPs) following acute symptoms. CASE PRESENTATION: We encountered 10 cases of epidemic keratoconjunctivitis from August to October 2017. All patients were adults with a mean age of 60.9 ± 10.0 years. The species D human adenovirus (HAdV)-54 was detected in the conjunctival scrapings of these patients. Fluorometholone instillation was administered during the first week for acute symptomatic relief. Case 1: A 64-year-old female was prescribed with fluorometholone instillation, which was discontinued after 1 week when her symptoms alleviated. One week after discontinuation of the instillation, she presented with blurred vision in her left eye with KPs and multiple stellate keratitis. The anterior chamber had no apparent cells. Her symptoms disappeared after 1 week of betamethasone instillation. Case 2: A 66-year-old female was prescribed with 0.1% fluorometholone instillation, which was discontinued within10 days. Three months after the appearance of initial symptoms, multiple subepithelial corneal infiltrates (MSI) appeared in her eyes. Stellate keratitis and dark-brown pigmentation were observed in the centres of MSI, with several cells in the anterior chamber. Betamethasone was prescribed, and MSI and stellate keratitis improved within 1 week. However, KPs were observed in the left eye. The instillation was continued for 3 more weeks until symptoms improved. CONCLUSIONS: MSI is an immune reaction that occurs after the disappearance of acute symptoms. Here, corneal findings and KPs were observed after improvement in eye redness and discontinuation of steroids. These symptoms were presumed to be secondary inflammation due to immune response to the adenoviral antigen. The clinical features of HAdV-54 keratoconjunctivitis on the ocular surface are initially moderate, but become active in the subacute to chronic phases. This may develop atypical findings, including stellate keratitis with KPs. Although early steroid administration can relieve acute symptoms, it may facilitate chronic corneal immunological reaction.

Enterovirus D68 respiratory infection in a children's hospital in Japan in 2015.

BACKGROUND: Outbreaks of enterovirus D68 (EV-D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV-D68 outbreak in the autumn of 2015 (September-October). The aim of this study was to compare EV-D68-specific polymerase chain reaction (PCR)-positive and EV-D68-specific PCR-negative patients. METHODS: Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV-D68-specific reverse transcription-PCR. EV-D68-specific PCR-positive and -negative patients were compared regarding demographic data and clinical information. RESULTS: A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV-D68 was detected in 40 samples (52.6%). Median age in the EV-D68-specific PCR-positive and -negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV-D68-positive group (3.0 days vs 5.0 days, P = 0.001). EV-D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered. CONCLUSIONS: More than half of the samples from the children admitted with respiratory symptoms were positive for EV-D68-specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection.

Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World.

Enteroviruses (EVs) are responsible for extremely large-scale, periodic epidemics in pediatric cohorts, particularly in East and Southeast Asia. Clinical presentation includes a diverse disease spectrum, including hand-foot and mouth disease (HFMD), aseptic meningitis, encephalitis, acute flaccid paralysis, and acute flaccid myelitis. HFMD is predominantly attributable to EV-A types, including the major pathogen EV-A71, and coxsackieviruses, particularly CV-A6, CV-A16, and CV-A10. There have been multiple EV-A71 outbreaks associated with a profound burden of neurological disease and fatal outcomes in Asia since the early 1980s. Efficacious vaccines against EV-A71 have been developed in China but widespread pediatric vaccination programs have not been introduced in other countries. Encephalitis, as a consequence of complications arising from HFMD infection, leads to damage to the thalamus and medulla oblongata. Studies in Vietnam suggest that myoclonus is a significant indicator of central nervous system (CNS) complications in EV-A71-associated HFMD cases. Rapid response in HFMD cases in children is imperative to prevent the progression to a CNS infection; however, prophylactic and therapeutic agents have not been well established internationally, therefore surveillance and functional studies including development of antivirals and multivalent vaccines is critically important to reduce disease burden in pediatric populations.

Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015.

Background: Acute flaccid myelitis (AFM) is an acute flaccid paralysis syndrome with spinal motor neuron involvement of unknown etiology. We investigated the characteristics and prognostic factors of AFM clusters coincident with an enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015. Methods: An AFM case series study was conducted following a nationwide survey from August to December 2015. Radiographic and neurophysiologic data were subjected to centralized review, and virology studies were conducted for available specimens. Results: Fifty-nine AFM cases (58 definite, 1 probable) were identified, including 55 children and 4 adults (median age, 4.4 years). The AFM epidemic curve showed strong temporal correlation with EV-D68 detection from pathogen surveillance, but not with other pathogens. EV-D68 was detected in 9 patients: 5 in nasopharyngeal, 2 in stool, 1 in cerebrospinal fluid (adult case), and 1 in tracheal aspiration, nasopharyngeal, and serum samples (a pediatric case with preceding steroid usage). Cases exhibited heterogeneous paralysis patterns from 1- to 4-limb involvement, but all definite cases had longitudinal spinal gray matter lesions on magnetic resonance imaging (median, 20 spinal segments). Cerebrospinal fluid pleocytosis was observed in 50 of 59 cases (85%), and 8 of 29 (28%) were positive for antiganglioside antibodies, as frequently observed in Guillain-Barré syndrome. Fifty-two patients showed variable residual weakness at follow-up. Good prognostic factors included a pretreatment manual muscle strength test unit score >3, normal F-wave persistence, and EV-D68-negative status. Conclusions: EV-D68 may be one of the causative agents for AFM, while host susceptibility factors such as immune response could contribute to AFM development.

Recombinant type Human mastadenovirus D85 associated with epidemic keratoconjunctivitis since 2015 in Japan.

The aim of this study was to report the emergence of a recombinant human mastadenovirus (HAdV) type 85 (HAdV-85) and to describe its genomic and clinical characteristics. The strains were detected and identified in Japan in cases of adenoviral conjunctivitis including epidemic keratoconjunctivitis (EKC). The type was designated as HAdV-85 based on the novel combination of penton base (P = HAdV-37), hexon (H = HAdV-19), and fiber (F = HAdV-8). The whole genome sequence determined for HAdV-85 was compared against sequences of other types in the same species. The results of the phylogenetic analysis suggested a recombinant origin between HAdV-53 and HAdV-64, which have been two major causes of adenoviral EKC in Japan over the past decade. During the period between 2008 and 2016 in Kumamoto city, southwest of Japan, 311 cases diagnosed with conjunctivitis were diagnosed as being the consequence of adenoviral infections. Among them, 11 cases were determined to have been caused by HAdV-85 since 2015. Thus, HAdV-85 could be an emerging causative agent of adenoviral conjunctivitis.

Species differences in circulation and inflammatory responses in children with common respiratory adenovirus infections.

Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but previous epidemiological studies lacked analysis of the characteristics of the inflammation. Consecutive patients <13 years old with acute febrile illness during a 2-year period were tested. HAdV strains were isolated from nasopharyngeal swabs, and molecular identification was performed by hexon, fiber, and species-specific PCR methods. Blood inflammatory markers, including the white blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187 patients were enrolled, and HAdV types were identified from 175 patients (93.5%). Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%, followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected predominantly in 1-year-old, whereas B and E were in older ages. Species C and B had seasonal circulation patterns, but E was found in only one season during the 2-year study period. The WBC count was highest in patients with species C. Eleven of the 29 tested serum cytokines were detected. Seven kinds, including G-CSF, IL-6, and TNF-α, were elevated in species C infections, whereas IL-10 was lowest in species C. Species differences in inflammatory responses, especially regarding serum cytokines were described in common pediatric HAdV infections. Species C causes the strongest inflammatory responses in young children.