Clinical characteristics and phylogenetic analysis of human enteric adenovirus type 41 (HAdV-F41) from children with gastroenteritis during SARS-CoV-2 pandemic.

Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the "zero-COVID" period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.

Hypofibrinogenemia is an independent predictor of hemophagocytic lymphohistiocytosis in children with sepsis.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition in children with sepsis. We herein aimed to identify clinical and laboratory predictors of HLH in children with sepsis. We conducted a retrospective study of 568 children with sepsis admitted to Guangdong Women and Children Hospital from January 2019 to June 2022. HLH, while rare (6.34%), proved to be a highly fatal complication (37.14%) in children with sepsis. Children with HLH had higher levels of aspartate aminotransferase, lactate dehydrogenase, triglycerides, and ferritin than children without HLH; conversely, they displayed decreased levels of neutrophils, hemoglobin, platelets, fibrinogen, and albumin. Additionally, the HLH group showed higher rates of prolonged fever (> 10 days), hepatomegaly, and splenomegaly than the non-HLH group. Our retrospective analysis identified hypofibrinogenemia (OR = 0.440, P = 0.024) as an independent predictor for the development of HLH in patients with sepsis. The optimal cutoff value for fibrinogen was found to be < 2.43 g/L. The area under the curve for diagnosing HLH was 0.80 (95% confidence interval: 0.73-0.87, P < 0.0001), with a sensitivity of 72.41% and specificity of 76.27%. Thus, hypofibrinogenemia emerges as a potentially valuable predictor for HLH in children with sepsis.

Distinct Lipids Profiles and Associations With Clinical Indicators and Gut Microbiota in Children With Prader-Willi Syndrome.

Lipid metabolism is closely linked to adiposity. Prader-Willi syndrome (PWS) is a typical genetic disorder causing obesity; however, the distinct lipidomic profiles in PWS children have not been thoroughly investigated. Herein, serum lipidomics analyses were simultaneously explored in PWS, simple obesity (SO), and normal children (Normal). Results indicated that the total concentration of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the PWS group were significantly deceased compared with both the SO and the Normal group. In contrast, compared with the Normal group, there was an overall significant increase in triacylglycerol (TAG) levels in both the PWS and the SO groups, with the highest found in SO group. Thirty-nine and 50 differential lipid species were screened among 3 groups: between obesity (PWS and SO) and the Normal group. Correlation analysis revealed distinct profiles in PWS that was different from other 2 groups. Notably, PC (P16:0/18:1), PE (P18:0-20:3), PE (P18:0-20:4)) showed significant negative correlation with body mass index (BMI) only in the PWS group. PE (P16:0-18:2) showed a negative association with BMI and weight in the PWS group, but significant positive correlation in the SO group; no statistically significant association was found in the Normal group. We also found a significant negative correlation between Blautia genus abundance and several significantly changed lipids, including LPC (14:0), LPC (16:0), TAG (C50:2/C51:9), TAG (C52:2/C53:9), TAG (C52:3/C53:10), and TAG (C52:4/C53:11), but no significant correlation in the Normal group and the SO group. Similarly, in the PWS group, the Neisseria genus was significantly negatively associated with acylcarnitine (CAR) (14:1), CAR (18:0), PE (P18:0/20:3), and PE (P18:0/20:4), and extremely positively associated with TAG (C52:2/C53:9); no obvious correlations were observed in the Normal group and the SO group.

Age-related seroprevalence trajectories of seasonal coronaviruses in children including neonates in Guangzhou, China.

OBJECTIVES: Four seasonal coronaviruses, including human coronavirus (HCoV)-229E and HCoV-OC43, HCoV-NL63, and HCoV-HKU1 cause approximately 15-30% of common colds in adults. However, the full landscape of the immune trajectory to these viruses that covers the whole childhood period is still not well understood. METHODS: We evaluated the serological responses against the four seasonal coronaviruses in 1886 children aged under 18 years by using enzyme-linked immunosorbent assay. The optical density values against each HCoV were determined from each sample. Generalized additive models were constructed to determine the relationship between age and seroprevalence throughout the whole childhood period. The specific antibody levels against the four seasonal coronaviruses were also tested from the plasma samples of 485 pairs of postpartum women and their newborn babies. RESULTS: The immunoglobulin (Ig) G levels of the four seasonal coronaviruses in the mother and the newborn babies were highly correlated (229E: r = 0.63; OC43: r = 0.65; NL63: r = 0.69; HKU1: r = 0.63). The seroprevalences in children showed a similar trajectory in that the levels of IgG in the neonates dropped significantly and reached the lowest level after the age of around 1 year (229E: 1.18 years; OC43: 0.97 years; NL63: 1.01 years; HKU1: 1.02 years) and then resurgence in the children who aged older than 1 year. Using the lowest level from the generalized additive models as our cutoff, the seroprevalences for HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were 98.11%, 96.23%, 96.23% and 94.34% at the age of 16-18 years. CONCLUSION: Mothers share HCoV-specific IgGs with their newborn babies and the level of maternal IgGs waned at around 1 year after birth. The resurgence of the HCoV-specific IgGs was found thereafter with the increase in age suggesting repeated infection occurred in children.

Maternal essential metals, thyroid hormones, and fetal growth: Association and mediation analyses in Chinese pregnant women.

BACKGROUND: Essential metals play critical roles in fetal growth and development, but results from human studies are inconsistent. Additionally, whether maternal thyroid hormone (TH) levels mediate the associations between essential metals and fetal growth remains unknown. METHODS: Data for analysis were extracted from the Information System of Guangdong Women and Children Hospital between January 2017 and December 2019. Maternal levels of essential metals [copper (Cu), zinc (Zn), magnesium (Mg), and iron (Fe)] and THs were measured at the second trimester. Multivariate linear models were introduced to evaluate the potential associations between maternal essential metals, thyroid functions, and fetal growth, and the possible mediation effects of thyroid functions were explored in the median analyses. RESULTS: A total of 4186 mother-infant pairs were included in the present study. Maternal Fe levels were found to significantly increase birth weight in 272.91 g (95 % CI: 15.59, 530.22) among anemia group. Maternal Cu levels were positively associated with increased free triiodothyronine/free thyroxine ratio (FT3/FT4). Negative associations of Fe and Mg levels with thyroid-stimulating hormone (TSH) concentrations were observed, accompanied with the positive associations in relation to FT3, FT4 and FT3/FT4 ratio. Mediation analyses suggested that 72.01 % of the associations between Fe levels and birth length might be mediated by FT3 levels. Additionally, 25.85 % of the Cu-birth length association and 44.53 % of the Fe-birth length association could be explained by FT3/FT4 ratio. CONCLUSION: Our findings suggest that maternal Cu, Mg, and Fe levels can alter TH concentrations, and maternal FT3 and FT3/FT4 ratio might be potential mediators on the developmental effects of Cu and Fe levels.

Rapid visual detection of dengue virus by combining reverse transcription recombinase-aided amplification with lateral-flow dipstick assay.

OBJECTIVES: Dengue caused by infection with the dengue virus (DENV) is endemic in the tropical and subtropical regions of the world and of greatest public health concern. With more large outbreaks in rural areas, the purpose of this study was to develop a point-of-care test using recombinase-aided amplification and lateral-flow dipsticks for rapidly detecting DENV in low-resource settings. METHODS: The primers for the recombinase-aided amplification (RAA) assay were designed based on 3' UTR of the DENV genome and screened. The RAA temperature, time and the concentration of primers were then optimized, as well as the lateral-flow dipstick assay (LFD) time. Finally, the diagnostic performance of the reverse transcription (RT)-RAA-LFD assay was evaluated using blood samples from 247 patients who were clinically suspected to be infected with DENV. RESULTS: The RAA primer pair F1/R2 was the optimal combination for detecting DENV. The RT-RAA was performed in an incubator block at 37°C for 20minutes, and the amplicons were visible in the flow dipsticks from a naked eye within 3minutes. The detection limit of the developed RT-RAA-LFD assay was 10 copies/µL with high specificity for DENV. Compared with commercial reverse transcription quantitative PCR assay, the kappa value of RT-RAA-LFD in the 247 clinical samples was 0.957. CONCLUSIONS: In this study, a rapid and visual point-of-care test based on RT-RAA and LFD assay was developed. It was found to be suitable for reliable detection of DENV in low-resource settings with limited laboratory capabilities and optimal storage conditions.

Rapid identification of Brucella sepsis/osteomyelitis in a 6-year old febrile patient with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry directly from positive blood culture: a case report.

BACKGROUND: Brucella is high-consequence pathogen and one of the most common seen laboratory- acquired infection pathogens. Quick and accurate detection of the pathogen will be of great important to reducing laboratory- acquired infection. Traditional biomedical reaction based method is time consumption, and mass spectrometry based method greatly reduces time consumption in pathogen identification. In the case presented here, we shared our experience in identification of Brucella directly from positive blood culture with mass spectrometry based method. CASE PRESENTATION: The patient is a 6-year boy with a history of three weeks fever accompanied with sweating and a pain at right patella. The patient also has a history of thalassemia and blood transfusion was performed previously admitted to our hospital. Two bottles of marrow culture and one bottle of blood culture were positive, and direct mass spectrometry from positive culture material revealed Brucella infection within 1 h. CONCLUSION: Clinical characters and laboratory findings of the patient presented here might help clinician in non-endemic region to made suspected brucellosis diagnose. Our experience in rapid identification of Brucella from positive blood culture with MALDI-TOF SP could help preventing laboratory-acquired infection of Brucella.

Clinical Characteristic and Pathogen Spectrum of Neonatal Sepsis in Guangzhou City from June 2011 to June 2017.

BACKGROUND Preterm and low birth weight (birth weight <2500 g) neonates are vulnerable to sepsis, and the causative pathogens vary in different regions and times. The objective of this study was to identify common organisms leading to neonatal sepsis and identify the characteristic of patients infected with different bacteria, which may help in the selection of antibiotics for empirical treatment. MATERIAL AND METHODS We retrospectively collected the clinical and microbiological data of neonates with culture-proven sepsis in our clinical setting from June 2011 to June 2017. The demography, composition, and distribution of the pathogens and the clinical characteristic of the cases infected with different bacteria were analyzed. RESULTS Of a total of 1048 bacteria that were isolated from patient samples, detailed clinical and microbiological data of 297 cases were available. Escherichia coli, Klebsiella pneumoniae, and coagulase-negative Staphylococcus (co-NS) were the top 3 isolated pathogens. Streptococcus agalactiae predominantly led to early-onset sepsis, while K. pneumoniae and Staphylococcus aureus mainly led to late-onset sepsis. K. pneumoniae was mainly acquired in the hospital. Leukopenia was more commonly seen than leukocytosis in our study, and patients infected with K. pneumoniae and Candida spp encountered more thrombocytopenia. CONCLUSIONS The results of our study revealed the composition of the pathogens of neonatal sepsis in our region and the clinical characteristic of sepsis caused by different bacteria; these data may help in the selection of antibiotics for empirical treatment of neonates with high risk of sepsis.

Clinical and epidemiological features of the 2014 large-scale dengue outbreak in Guangzhou city, China.

BACKGROUND: Dengue virus is transmitted by mosquito around the tropical and sub-tropical regions. There was a large-scale dengue epidemic in Guangdong province, China during 2014 and around fifty thousands dengue fever cases, including six deaths, have been reported. In this study, we aimed to understand the clinical characteristics of hospitalized patients with laboratory-confirmed dengue virus (DENV) infection and determined the origin of the virus from the outbreak. METHODS: We have summarized the data from 138 hospitalized patients who were laboratory confirmed for dengue infection in Guangzhou city. Patients were classified as either non-severe dengue fever or severe dengue fever according to the guidelines from the WHO. Viral serotypes were determined by real time RT-PCR. Genetic sequences of the envelope and non-structural genes were amplified and analyzed from the serum samples of eleven patients. RESULTS: Co-circulation of dengue serotype 1 and 2 were identified from the outbreak. Patients infected by serotype 1 or 2 showed similar clinical features. Patients with severe dengue fever showed prolonged hospitalization and significant impairment of organ functions. Four samples from serotype 1 and five samples from serotype 2 were closely related respectively and clustered with Guangzhou isolates from previous years. The remaining isolates of serotype 1 were related to viruses found in Malaysia, India, Bangladesh and Singapore. CONCLUSION: The phylogenetic grouping of Guangdong isolates suggests that dengue is no longer an imported disease in China. Analysis of the isolates obtained in this study together with the size of the outbreak are suggestive of endemic circulation in Guangdong province.