Distinct clinical features of transplanted children with Parvovirus B19 infection.

BACKGROUND: The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven't been comprehensively described. METHODS: We searched the medical records of all the transplant recipients who attended the Children's Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children. RESULTS: A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system. CONCLUSIONS: Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.

Diagnosis of mixed infection and a primary immunodeficiency disease using next-generation sequencing: a case report.

Major Histocompatibility Complex Class II (MHC II) deficiency is a rare primary immunodeficiency disorder (PID) with autosomal recessive inheritance pattern. The outcome is almost fatal owing to delayed diagnosis and lacking of effective therapy. Therefore, prompt diagnosis, timely and effective treatment are critical. Here, we report a 117-day-old boy with diarrhea, cough, cyanosis and tachypnea who was failed to be cured by empiric antimicrobial therapy initially and progressed to severe pneumonia and respiratory failure. The patient was admitted to the pediatric intensive care unit (PICU) immediately and underwent a series of tests. Blood examination revealed elevated levels of inflammatory markers and cytomegalovirus DNA. Imaging findings showed signs of severe infection of lungs. Finally, the diagnosis was obtained mainly through next-generation sequencing (NGS). We found out what pathogenic microorganism he was infected via repeated conventional detection methods and metagenomic next-generation sequencing (mNGS) of sputum and bronchoalveolar lavage fluid (BALF). And his whole exome sequencing (WES) examination suggested that CIITA gene was heterozygous mutation, a kind of MHC II deficiency diseases. After aggressive respiratory support and repeated adjustment of antimicrobial regimens, the patient was weaned from ventilator on the 56th day of admission and transferred to the immunology ward on the 60th day. The patient was successful discharged after hospitalizing for 91 days, taking antimicrobials orally to prevent infections post-discharge and waiting for stem cell transplantation. This case highlights the potential importance of NGS in providing better diagnostic testing for unexplained infection and illness. Furthermore, pathogens would be identified more accurately if conventional detection techniques were combined with mNGS.

Surveillance and epidemiological characterization of human adenovirus infections among outpatient children with acute gastroenteritis during the COVID-19 epidemic in Shanghai, China.

BACKGROUND: Human adenovirus (HAdV) has been recognized as one of the common enteric viruses associated with acute gastroenteritis (AGE) in children. The aim of this study was carried out to illustrate the epidemiological characterization of HAdV Infections among children younger than 15 years in Shanghai during COVID-19. METHODS: During May 2020 and April 2022, 1048 fecal samples were collected from children ≤ 15 years diagnosed with AGE in the Children's Hospital of Fudan University. HAdV was identified by PCR and sequenced with specific primers. All the obtained sequences were analyzed by MEGA (version 6.0). Demographic information and clinical features data were also collected and analyzed. RESULTS: In total, 97 (9.3%, 97/1048) samples were detected to be HAdV during May 2020 and April 2022. We found an atypical upsurge in HAdV infection in the year 2021 after a major suppression in the year 2020. Approximately 84.5% (82/97) of HAdV-infected children were aged 0-60 months. Among the 97 HAdV-positive samples, only two species and five genotypes were detected. HAdV-F (88.7%, 86/97) was the most prevalent species and HAdV-F41 (87.6%, 85/97) was the most common genotype. Diarrhea, vomiting, and fever were the main clinical manifestations in children infected with HAdV. The children aged from 0 to 12 months showed simpler patterns of clinical presentation than those of children older than 13 months. CONCLUSIONS: Our findings described the epidemiological changes of HAdV infection in children with AGE during the COVID-19, which further underscored the importance of continuous surveillance of HAdV at both local and global scales.

Association of CDSS score and 60-day mortality in Chinese patients with non-APL acute myeloid leukemia: a retrospective cohort study.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, and is one of the triggers of DIC, the latter is an essential factor in the early death of patients with AML. However, the timely identification of DIC remains a challenge. The Chinese DIC Scoring System (CDSS) is a common consensus widely used in China; but, there are few reports on its application in patients with AML. We undertake this retrospective cohort study to investigate the association between CDSS score and 60-day mortality. CDSS scores were evaluated after admission. The outcome was all-cause 60-day mortality. Multivariate Cox regression analyses were performed to calculate the adjusted hazard ratio (HR) and the corresponding 95% confidence interval (CI). Survival curves were plotted by Kaplan-Meier and log-rank analyses. Subgroup analyses were stratified by relevant effect covariates. A total of 570 consecutive patients with primary AML were included. We found an association between a 39% increase in 60-day mortality and a 1 point increase in CDSS score (HR = 1.39, 95% CI 1.25-1.54), which was associated with a 189% increase in 60-day mortality in CDSS scores ≥ 6 compared with that in the CDSS scores < 6 (HR = 2.89, 95% CI 1.91-4.38). After adjusting for all potential con-founders, a 27% and a 198% increase were observed (HR = 1.27, 95% CI 1.01-1.61; HR = 2.98, 95% CI 1.24-7.19), respectively. There is association between 60-day mortality and CDSS score in patients with AML. These findings may help hematologists in making informed treatment decisions.

Epidemiology and clinical characteristics of Epstein-Barr virus infection among children in Shanghai, China, 2017-2022.

Objective: To investigate the epidemiology and infectious characteristics of Epstein-Barr virus (EBV) infection among children in Shanghai, China from 2017 to 2022. Methods: We conducted a retrospective analysis of 10,260 inpatient patients who were subjected EBV nucleic acid testing from July 2017 to December 2022. Demographic information, clinical diagnosis, laboratory findings, etc. were collected and analyzed. EBV nucleic acid testing were performed by real-time PCR. Results: A total of 2192 (21.4%) inpatient children were EBV-positive, with the average age of 7.3 ± 0.1 y. EBV detection was stable from 2017 to 2020 (26.9~30.1%), but showed essential decreases in 2021 (16.0%) and 2022 (9.0%). EBV was highest (>30%) detected from three quarters (Q) including 2018-Q4, 2019-Q4 and 2020-Q3. There were 24.5% of EBV coinfection with other pathogens, including bacteria (16.8%), other viruses (7.1%) and fungi (0.7%). EBV viral loads increased when coinfecting with bacteria ((142.2 ± 40.1) ×104/mL) or other viruses ((165.7 ± 37.4) ×104/mL). CRP significantly increased in EBV/fungi coinfection, while procalcitonin (PCT) and IL-6 showed remarkable increases in EBV/bacteria coinfection. Most (58.9%) of EBV-associated diseases belonged to immune disorders. The primary EBV-related diseases were systemic lupus erythematosus (SLE, 16.1%), immunodeficiency (12.4%), infectious mononucleosis (IM, 10.7%), pneumonia (10.4%) and Henoch-schonlein purpura (HSP, 10.2%). EBV viral loads were highest ((233.7 ± 27.4) × 104/mL) in patients with IM. Conclusion: EBV was prevalent among children in China, the viral loads increased when coinfecting with bacteria or other viruses. SLE, immunodeficiency and IM were the primary EBV-related diseases.

Comparison of Respiratory Pathogens in Children With Lower Respiratory Tract Infections Before and During the COVID-19 Pandemic in Shanghai, China.

Objectives: This study aimed to assess the impact of COVID-19 on the prevalence of respiratory pathogens among hospitalized children with lower respiratory tract infections (LRTIs) in Shanghai. Methods: Respiratory specimens were collected from children with LRTIs in Children's Hospital of Fudan University from February 2019 to January 2021 and common respiratory pathogens were detected using multiplex PCR. The data of 13 respiratory pathogens were analyzed and compared between the year of 2020 (from February 2020 to January 2021) and 2019 (from February 2019 to January 2020). Results: A total of 1,049 patients were enrolled, including 417 patients in 2019 and 632 patients in 2020. In 2020, 27.53% of patients were tested positive for at least one pathogen, which was significantly lower than that in 2019 (78.66%). The top three pathogens were Mycoplasma pneumoniae (Mp), human adenovirus (ADV) and human rhinovirus (RV) in 2019, whereas RV, human respiratory syncytial virus (RSV) and human parainfluenza virus (PIV) were the predominant ones in 2020. The positive rates of Mp, ADV, RV, PIV, Influenza virus B (InfB), H3N2, and H1N1 were significantly decreased in 2020. RV was the most detectable respiratory pathogen in 2020, and become the most frequent pathogen in all five age groups. PIV had a high prevalence from October to December 2020 which was even higher than that in 2019. Influenza virus A (InfA) was not detected in 2020. Co-infection was significantly less frequent in 2020. Conclusion: The public health interventions aiming to eliminate COVID-19 have great impact on the prevalence of common respiratory pathogens. The prevalence of RV and PIV reminds us a possible resurgence of some pathogens.

Propranolol inhibits the angiogenic capacity of hemangioma endothelia via blocking ß-adrenoceptor in mast cell.

BACKGROUND: Propranolol, a non-selective blocker of the ß-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear. METHODS: HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot. RESULTS: In propranolol-treated HMC-1s, the expressions of ADRB1 (ß1-AR) and ADRB2 (ß2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. CONCLUSIONS: Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both ß1 and ß2 adrenoceptor in mast cell. IMPACT: Treated with propranolol, ß1, and ß2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both ß1 and ß2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.

Molecular and epidemiological characterization of human adenovirus and classic human astrovirus in children with acute diarrhea in Shanghai, 2017-2018.

BACKGROUND: In addition to rotavirus and norovirus, human adenovirus (HAdV) and classic human astrovirus (classic HAstV) are important pathogens of acute diarrhea in infants and young children. Here, we present the molecular epidemiology of HAdV and classic HAstV in children with acute diarrhea in Shanghai. METHODS: Fecal specimens were collected from 804 outpatient infants and young children diagnosed with acute diarrhea in Shanghai from January 2017 to December 2018. All of the samples were screened for the presence of HAdV and classic HAstV. HAdV and classic HAstV were detected using traditional PCR and reverse-transcription PCR, respectively. All of the HAdV and classic HAstV positive samples were genotyped by phylogenetic analysis. RESULTS: Among the 804 fecal samples, 8.58% (69/804) of samples were infected with either HAdV or classic HAstV, and five were co-infected with two diarrhea viruses. The overall detection rates of HAdV and classic HAstV were 3.47% (28/804) and 5.22% (42/804), respectively. Four subgroups (A, B, C, and F) and seven genotypes (HAdV-C1, -C2, -B3, -C5, -A31, -F40, and -F41) of HAdV were detected. Subgroup F had the highest constituent ratio at 64.29% (18/28), followed by non-enteric HAdV of subgroup C (21.43%, 6/28) and subgroup B 10.71% (3/28). HAdV-F41 (60.71%, 17/28) was the dominant genotype, followed by HAdV-C2 (14.29%, 4/28) and HAdV-B3 (10.71%, 3/28). Two genotypes of classic HAstV (HAstV-1 and HAstV-5) were identified in 42 samples during the study period; HAstV-1 (95.24%, 40/42) was the predominant genotype, and the other two strains were genotyped as HAstV-5. No significant differences were found between boys and girls in the detection rates of HAdV (P = 0.604) and classic HAstV (P = 0.275). Over half of the HAdV infections (82.14%, 23/28) and classic HAstV infections (66.67%, 28/42) occurred in children less than 36 months. Seasonal preferences of HAdV and classic HAstV infections were summer and winter, respectively. In this study, the common clinical symptoms of children with acute diarrhea were diarrhea, vomiting, fever and abdominal pain. CONCLUSIONS: Our findings indicate that HAdV and classic HAstV play important roles in the pathogenesis of acute diarrhea in children in Shanghai. Systematic and long-term surveillance of HAdV and classic HAstV are needed to monitor their prevalence in children and prevent major outbreak.

Whole transcriptome profiling reveals major cell types in the cellular immune response against acute and chronic active Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a common human pathogen that infects over 95% of the population worldwide. In the present study, the whole transcriptome microarray data were generated from peripheral blood mononuclear cells from Chinese children with acute infectious mononucleosis (AIM) and chronic active EBV infection (CAEBV) that were also compared with a publicly available microarray dataset from a study of American college students with AIM. Our study characterized for the first time a broad spectrum of molecular signatures in AIM and CAEBV. The key findings from the transcriptome profiling were validated with qPCR and flow cytometry assays. The most important finding in our study is the discovery of predominant γδ TCR expression and γδ T cell expansion in AIM. This finding, in combination with the striking up-regulation of CD3, CD8 and CD94, suggests that CD8+ T cells and CD94+ NK cells may play a major role in AIM. Moreover, the unique up-regulation of CD64A/B and its significant correlation with the monocyte marker CD14 was observed in CAEBV and that implies an important role of monocytes in CAEBV. In conclusion, our study reveals major cell types (particularly γδ T cells) in the host cellular immune response against AIM and CAEBV.

Detection and Molecular Characterization of Human Adenovirus Infections among Hospitalized Children with Acute Diarrhea in Shanghai, China, 2006-2011.

Background: Human adenovirus (HAdV) is considered a significant enteropathogen associated with sporadic diarrhea in children. However, limited data are available regarding the epidemiology of HAdV in hospitalized children with viral diarrhea in Shanghai. The aim of this study was to characterize the epidemiology of HAdVs and describe their association with acute diarrhea in hospitalized children. Methods: A total of 674 fecal samples were subjected to PCR or RT-PCR to detect RVA, HuCV, HAstV, and HAdV. Results: HAdV infections were detected in 4.7% (32/674) of specimens, with detection rates of 13.4% (11/82), 4.6% (8/174), 3.2% (4/124), 4.1% (3/74), 2.0% (2/100), and 3.3% (4/120) from 2006 to 2011, respectively. Comprehensive detection of the four viruses revealed the presence of a high percentage (90.6%) of coinfections among HAdV-positive samples, where HAdV+RVA was the most prevalent coinfection. Of the 32 HAdV-positive samples, 50.0% (16/32) were classified as HAdV-41, and 18.8% (6/32) were classified as HAdV-3. Almost 94.0% of children infected with HAdV were less than 24 months of age. Conclusions: These results clearly indicated diversity across the HAdV genotypes detected in inpatient children with acute diarrhea in Shanghai and suggested that HAdVs play a role in children with acute diarrhea.

Molecular characterization and multiple infections of rotavirus, norovirus, sapovirus, astrovirus and adenovirus in outpatients with sporadic gastroenteritis in Shanghai, China, 2010-2011.

Rotavirus (RV), norovirus (NoV), sapovirus (SaV), human astrovirus (HAstV) and human adenovirus (HAdV) are significant because they are the most common pathogens that cause diarrhea in young children. The aim of this study was to investigate the genetic characteristics and compare the roles of these five viruses in outpatient children with diarrhea in Shanghai. A total of 436 fecal samples were collected from pediatric patients with acute gastroenteritis from January 2010 to December 2011. The selected samples were subjected to reverse transcription PCR (RT-PCR) or PCR to detect and genotype RV, NoV, SaV, HAstV and HAdV. RV (43.3 %, 189/436) was the most prevalent virus, followed by NoV (28.9 %, 126/436), HAdV (7.1 %, 31/436). HAstV (1.8 %, 8/436) and SaV (0.5 %, 2/436). The percentage of multiple infection cases was 14.9 % (65/436), and RV + NoV was the predominant mixed infection. The RV genotype combinations of P[8]G3 (52/189, 27.5 %), P[8]G1 (51/189, 26.9 %) and P[8]G9 (48/189, 25.4 %) occurred most frequently. The predominant NoV genotype was GII.4 (73.0 %, 92/126), and the majority of GII.4 clustered as GII.4-2006b (65.2 %, 60/92). Two of the SaV cases were identified as GI.2 and GII.1. All HAstV-positive samples belonged to HAstV-1. The predominant HAdV type was HAdV-41 (45.2 %, 14/31). This study clearly shows the diversity of the viral causative agents of acute gastroenteritis in outpatient children in Shanghai, which will provide baseline information for future vaccination strategies and development in this area.