Epidemiology of endemic human coronavirus infection during the COVID-19 pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that also includes endemic human coronaviruses (HCoVs) types OC43, HKU1, 229E, and NL63. HCoVs share extensive sequence homology with SARS-CoV-2. It has been assumed that HCoV infection occur primarily in winter and spring in Japan before the coronavirus disease 2019 (COVID-19) pandemic and that its frequency is the same for all age groups. METHODS: Nasopharyngeal swab samples were collected for HCoVs and SARS-CoV-2. All medical data were retrospectively analyzed. Our primary objective was to describe the epidemiology of HCoV in the Furano, Japan during the COVID-19 pandemic. Our secondary objective was to compare the prevalence of HCoV with that of SARS-CoV-2. RESULTS: From September 2020 to August 2022, 113 (6.2 %) of 1823 cases were positive for any HCoV. The HCoV-NL63 activity peaked in January-March 2021. The HCoV-OC43 activity peaked in June-August 2021. HCoVs were mostly detected at age ≤11 years and most frequently at age ≤2 years. HCoVs showed high detection in 2021, while SARS-CoV-2 showed moderate detection in 2020-2021, but significantly increased in 2022. CONCLUSIONS: During the COVID-19 pandemic, HCoV-OC43 activity peaked in the summer. The frequency of HCoV infection varied widely by age group and was higher among those aged ≤11 years. These were different from those reported before the COVID-19 pandemic. These findings suggest that the disease dynamics of HCoVs remain unclear and that continued surveillance is essential in the post-COVID-19 pandemic.

Factors associated with viral RNA shedding and evaluation of potential viral infectivity at returning to school in influenza outpatients after treatment with baloxavir marboxil and neuraminidase inhibitors during 2013/2014-2019/2020 seasons in Japan: an observational study.

BACKGROUND: This study assessed the differences in daily virus reduction and the residual infectivity after the recommended home stay period in Japan in patients infected with influenza and treated with baloxavir (BA), laninamivir (LA), oseltamivir (OS), and zanamivir (ZA). METHODS: We conducted an observational study on children and adults at 13 outpatient clinics in 11 prefectures in Japan during seven influenza seasons from 2013/2014 to 2019/2020. Virus samples were collected twice from influenza rapid test-positive patients at the first and second visit 4-5 days after the start of treatment. The viral RNA shedding was quantified using quantitative RT-PCR. Neuraminidase (NA) and polymerase acidic (PA) variant viruses that reduce susceptibility to NA inhibitors and BA, respectively, were screened using RT-PCR and genetic sequencing. Daily estimated viral reduction was evaluated using univariate and multivariate analyses for the factors such as age, treatment, vaccination status, or the emergence of PA or NA variants. The potential infectivity of the viral RNA shedding at the second visit samples was determined using the Receiver Operator Curve based on the positivity of virus isolation. RESULTS: Among 518 patients, 465 (80.0%) and 116 (20.0%) were infected with influenza A (189 with BA, 58 with LA, 181 with OS, 37 with ZA) and influenza B (39 with BA, 10 with LA, 52 with OS, 15 with ZA). The emergence of 21 PA variants in influenza A was detected after BA treatment, but NA variants were not detected after NAIs treatment. Multiple linear regression analysis showed that the daily viral RNA shedding reduction in patients was slower in the two NAIs (OS and LA) than in BA, influenza B infection, aged 0-5 years, or the emergence of PA variants. The residual viral RNA shedding potentially infectious was detected in approximately 10-30% of the patients aged 6-18 years after five days of onset. CONCLUSIONS: Viral clearance differed by age, type of influenza, choice of treatment, and susceptibility to BA. Additionally, the recommended homestay period in Japan seemed insufficient, but reduced viral spread to some extent since most school-age patients became non-infectious after 5 days of onset.

Clinical effectiveness of baloxavir marboxil against influenza in three seasons.

BACKGROUND: Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza. METHODS: A prospective observational study was performed during 2017-2018, 2018-2019, and 2019-2020 influenza seasons. The primary endpoint of this study was to compare the duration of fever between patients who received baloxavir and those who received oseltamivir. RESULTS: A total of 235 influenza-infected patients (3-18 years of age), including 91 who received oseltamivir and 144 who received baloxavir, were enrolled. The proportions of influenza A(H3N2) virus, influenza A(H1N1)pdm09 virus, and influenza B virus-infected patients were 31.5%, 42.6%, and 26.0%, respectively. Patients who received oseltamivir were significantly younger than those who received baloxavir. Univariate analyses showed that the duration of fever was shorter with baloxavir than with oseltamivir against influenza virus overall, influenza A virus, influenza B virus, and influenza A(H1N1)pdm09 virus, but not for influenza A(H3N2) virus. In multivariate analyses, hazard ratios for influenza virus overall (0.53 [95% CI, 0.38-0.73]), influenza B virus (0.16 [95% CI, 0.07-0.41]), and influenza A(H1N1)pdm09 virus (0.55 [95% CI, 0.32-0.93]) were significantly lower in the patients who received baloxavir than those who received oseltamivir. However, the differences between influenza A virus and influenza A(H3N2) virus were not significant between the two groups. CONCLUSION: For influenza virus overall, influenza B virus, and influenza A(H1N1)pdm09 virus, baloxavir treatment resulted in shorter duration of fever than oseltamivir treatment, but not for influenza A virus and influenza A(H3N2) virus.

Evaluation of a Novel Immunochromatographic Assay Using Monoclonal Antibodies against the Matrix Protein of Human Metapneumovirus.

BACKGROUND: The aim of this study was to determine the sensitivity and specificity of a novel immunochromatographic (IC) assay (APD1806) using monoclonal antibodies against the matrix (M) protein of human metapneumovirus (hMPV) for detection of hMPV from nasopharyngeal swab samples based on the results of real-time RT-PCR. METHODS: Nasopharyngeal swab samples taken from 189 patients aged 0 - 5 years who were suspected of having respiratory tract infections associated with hMPV were used in this study. The samples were tested both by the IC assay and by real-time RT-PCR for detection of hMPV. RESULTS: The sensitivity and specificity of the IC assay for detection of hMPV were 88.8% (95/107) and 92.7% (76/82), respectively. CONCLUSIONS: The IC assay using monoclonal antibodies against the M protein of hMPV is an accurate and fast assay that is suitable as a diagnostic tool for hMPV infection. The optimal timing of the IC assay is 12 hours or more after the onset of fever due to hMPV infection.

The First Pediatric Patients with Coronavirus Disease 2019 (COVID-19) in Japan: Risk of Co-Infection with Other Respiratory Viruses.

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.

Acute Pharyngitis Associated With Streptococcus dysgalactiae Subspecies equisimilis in Children.

BACKGROUND AND OBJECTIVES: The importance of Streptococcus dysgalactiae subsp. equisimilis (SDSE) in causing sporadic pharyngitis in children remains controversial. The aims of this study were (1) to report the incidence and (2) to compare the epidemiologic and clinical features of patients with SDSE to those with Streptococcus pyogenes (SP). METHODS: A prospective study was conducted on acute pharyngitis associated with SDSE in children over a 2-year period. SDSE was identified using a phenotypic method, M protein gene (emm) analysis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Patients with positive SDSE or SP cultures received cephalosporins for 5 days and were followed up. The emm genotyping and specific virulence genes analyses were performed. RESULTS: From 3416 throat cultures, 67 isolates (2.0%) were identified as SDSE and 515 (15.1%) were identified as SP. The mean age of patients with SDSE (8.3 years) was older than those with SP (6.6 years; P < 0.01). There was minimal seasonal variation in the isolation rates of SDSE. The febrile patients' rates, gender distribution, cervical lymph node adenopathy rates, hospitalization rates, eradication and failure rates and the nonsuppurative sequelae between patients with SDSE and SP were similar. All SDSE isolates possessed important virulence genes. The emm genotyping of SDSE showed high strain diversity. CONCLUSIONS: The incidence of acute pharyngitis associated with accurately identified SDSE was 2/15 of that with SP. Epidemiologic and clinical features of acute pharyngitis associated with SDSE are indistinguishable from those with SP, with the exception of age and seasonal variation.

Comparison of Oropharyngeal and Nasopharyngeal Swab Specimens for the Detection of Mycoplasma pneumoniae in Children with Lower Respiratory Tract Infection.

The oropharyngeal swab specimen was superior to the nasopharyngeal swab specimen for the detection of Mycoplasma pneumoniae in children with lower respiratory tract infection. The oropharyngeal loop-mediated isothermal amplification had 100% sensitivity and specificity compared with polymerase chain reaction testing, whereas the oropharyngeal rapid antigen detection test using immunochromatographic assay had relatively low sensitivity (66%) and reasonable specificity (90.7%).

Clinical findings in 10 children with H275Y influenza A(H1N1)pdm09 virus infection.

BACKGROUND: Little is known about the clinical effectiveness of neuraminidase inhibitors against H275Y influenza A(H1N1)pdm09 virus. A cluster of H275Y influenza A(H1N1)pdm09 virus with cross-resistance to oseltamivir and peramivir was detected among untreated community patients in Hokkaido, Japan, during the 2013-2014 influenza season. METHODS: This was a retrospective observational study. Specimens from nasopharyngeal swabs underwent rapid testing and single-nucleotide polymorphism identification on real-time polymerase chain reaction. We collected clinical data from the H275Y group and a 275H wild-type comparison group. All children were given one of four neuraminidase inhibitors. RESULTS: Twenty-eight children infected with influenza A(H1N1)pdm09 virus were analyzed. Ten viruses had the H275Y substitution, while the other 18 had wild-type 275H. Mean fever duration after treatment and after onset was 25.3 h (95%CI: 14.1-36.5) and 48.9 h (95%CI: 34.4-63.3) in the H275Y group, respectively, and 26.1 h (95%CI: 18.7-33.6) and 46.3 h (95%CI: 35.7-56.8) in the 275H group, respectively. In the H275Y group, three patients were treated with oseltamivir, one with peramivir, five with zanamivir, and one with laninamivir. All of them had mild symptoms and received only outpatient care. Fever duration was 7.5-21.0 h and 18.0-66.0 h after treatment and after onset, respectively, in the patients treated with oseltamivir and peramivir, and 20.5-42.0 h and 42.0-88.0 h, respectively, in those treated with zanamivir and laninamivir. CONCLUSION: Fever in the H275Y children treated with oseltamivir and peramivir resolved rapidly during the 2013-2014 influenza season.

Genetic point-of-care diagnosis of Mycoplasma pneumoniae infection using LAMP assay.

BACKGROUND: Mycoplasma pneumoniae (MP) is a major pathogen of lower respiratory tract infection (LRTI) in children. A rapid diagnostic method during the acute phase is required for the prescription of effective antibiotics. METHODS: A prospective, single-centered study was conducted on community-acquired LRTI in children. We regarded the day of fever onset as the first day of illness. In part 1, we studied 191 patients with signs of LRTI. We compared diagnostic reliability using loop-mediated isothermal amplification (LAMP) assay and serological testing at the first visit. In part 2, we evaluated the clinical characteristics of 117 patients with positive LAMP assay. RESULTS: In part 1, 31 patients met the definite MP infection criteria. LAMP assay had a sensitivity of 96.8% and specificity of 100%, whereas enzyme immunoassay had a sensitivity of 38.7% and specificity of 76.9%, and particle agglutination test had a sensitivity of 19.4% and specificity of 93.1%. In part 2, of 106 patients with fever, 100 patients were diagnosed by the day 7 of illness. The diagnosis was made a mean of 3.5 ± 2.1 days after the onset of fever. CONCLUSIONS: LAMP assay had excellent sensitivity and specificity for the detection of acute MP infection at the first visit. This assay can diagnose MP infection during the very acute phase. LAMP assay is appropriate for genetic point-of-care diagnosis of MP infection in hospital laboratories.

The role of N-terminal pro-B-type natriuretic peptide in the diagnosis of congestive heart failure in children. - Correlation with the heart failure score and comparison with B-type natriuretic peptide -.

BACKGROUND: Both B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are useful biomarkers for the assessment of congestive heart failure (CHF) in adults. The purpose of this study was to determine whether BNP and NT-proBNP levels could be used to stratify the severity of CHF in children. METHODS AND RESULTS: The study comprised 181 children with CHF and 232 healthy children aged from 4 months to 14 years who were categorized into CHF grades I, II, III and IV according to the modified Ross scoring system. The plasma BNP and serum NT-proBNP levels were significantly correlated with increasing CHF grades. The NT-proBNP levels were significantly different among the 4 CHF grades. However, only 2 significant differences were observed in the BNP levels between each CHF grade. NT-proBNP testing with cut-off points of >438 pg/ml (> or =grade II), >1,678 pg/ml (> or =grade III) and >7,734 pg/ml (grade IV) in the patients below 3 years of age, and >295 pg/ml (> or =grade II), >1,545 pg/ml (> or =grade III) and >3,617 pg/ml (grade IV) in those above 3 years of age was determined to be highly sensitive and specific by receiver operating characteristic analysis. CONCLUSIONS: The blood levels of BNP and NT-proBNP therefore reflect the severity of CHF in children. In particular, NT-proBNP is a useful biomarker for evaluating CHF in children.

Relationship between erythropoietin levels both in cord serum and amniotic fluid at birth and abnormal fetal heart rate records.

BACKGROUND: Our data in rats suggest that an elevated amniotic fluid erythropoietin (EPO) level at birth indicates antepartum fetal hypoxia. However, the short gestation period in rats does not permit a direct comparison of our data with humans. METHODS: We conducted a retrospective study of the relationship between EPO levels at birth and abnormal fetal heart rate (FHR) records in 113 infants. RESULTS: Among the cesarean section group, the cord serum and amniotic fluid EPO levels in the infants with antepartum abnormal FHR records were significantly higher than those in the control infants. Among the vaginal delivery group, the cord serum EPO levels in the infants with intrapartum abnormal FHR records was significantly higher than that in the control infants. The EPO levels in either cord serum and amniotic fluid discriminated between infants with antepartum abnormal FHR records. The control infants had a sensitivity of 83% and a specificity of 96%. Six of the seven infants with abnormal EPO levels in both cord serum and amniotic fluid had symptoms of prolonged fetal hypoxia. Five infants with abnormal EPO levels in only cord serum had symptoms of acute fetal hypoxia before birth. Four of the 14 infants with abnormal EPO levels at birth had poor outcomes in the neonatal period. CONCLUSIONS: We concluded that EPO levels in both cord serum and amniotic fluid at birth are valuable for determining the timing of fetal hypoxia and may predict the outcome in the neonatal period.