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.

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.

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.

A multicentre study on the incidence of respiratory viruses in children with community-acquired pneumonia requiring hospitalization in the setting of the zero-COVID policy in China.

BACKGROUND: Stringent nonpharmaceutical interventions (NPIs) have been implemented worldwide to combat the COVID-19 pandemic, and the circulation and seasonality of common respiratory viruses have subsequently changed. There have been few multicentre studies or comparisons of the prevalence of respiratory viruses accounting for community-acquired pneumonia (CAP) in hospitalized children between the pre-COVID period and the period after community and school reopening in the setting of the zero-COVID policy. METHODS: We included 1543 children with CAP who required hospitalization from November 1, 2020 to April 30, 2021 (period 1), and 629 children with the same conditions from November 1, 2018, to April 30, 2019 (period 2), in our study. All respiratory samples from these patients were screened for six respiratory viruses (respiratory syncytial virus [RSV], adenovirus [ADV], influenza A virus [Flu A], influenza B virus [Flu B], parainfluenza virus type 1 [PIV1], and parainfluenza virus type 3 [PIV3]) using a multiplex real-time PCR assay. RESULTS AND CONCLUSIONS: The median ages of the enrolled patients at the time of diagnosis were 1.5 years and 1.0 years for period 1 and period 2, respectively. In period 1, viral pathogens were detected in 50.3% (776/1543) of the enrolled patients. The most frequently identified viral pathogen was RSV (35.9%, 554/1543), followed by PIV3 (9.6%, 148/1543), PIV1 (3.6%, 56/1543), ADV (3.4%, 52/1543), Flu A (1.0%, 16/1543), and Flu B (0.8%, 13/1543). The total detection rates of these six viruses in the peak season of CAP were at the pre-COVID level. The prevalence of Flu A decreased dramatically, and circulation activity was low compared to pre-COVID levels, while the incidence of PIV3 increased significantly. There were no significant differences in the detection rates of RSV, ADV, Flu B, and PIV1 between the two periods. Our results showed that respiratory viruses accounted for CAP in hospitalized children at pre-COVID levels as communities and schools reopened within the zero-COVID policy, although the prevalence aetiology spectrum varied.

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.

The changing pattern of common respiratory and enteric viruses among outpatient children in Shanghai, China: Two years of the COVID-19 pandemic.

Nonpharmaceutical interventions (NPIs) taken to combat the coronavirus disease 2019 (COVID-19) pandemic have not only decreased the spread of severe acute respiratory syndrome coronavirus 2 but also have had an impact on the prevalence of other common viruses. This study aimed to investigate the long-term impact of NPIs on common respiratory and enteric viruses among children in Shanghai, China, as NPIs were relaxed after June 2020. The laboratory results and clinical data of outpatient children with acute respiratory tract infections (ARTI) and acute gastroenteritis (AGE) were analyzed and compared between the post-COVID-19 period (from June 2020 to January 2022) and pre-COVID-19 period (from June 2018 to January 2020). A total of 107 453 patients were enrolled from June 2018 to January 2022, including 43 190 patients with ARTI and 64 263 patients with AGE. The positive rates of most viruses decreased during the post-COVID-19 period, with the greatest decrease for influenza A (-0.94%), followed by adenoviruses (AdV) (-61.54%), rotaviruses (-48.17%), and influenza B (-40%). However, the positive rates of respiratory syncytial virus (RSV) and enteric AdV increased during the post-COVID-19 period as the NPIs were relaxed. Besides this, in the summer of 2021, an unexpected out-of-season resurgence of RSV activity was observed, and the resurgence was more prominent among children older than 5 years. The effectiveness of the current relaxed NPIs in control of common respiratory and enteric viruses was variable. Relaxation of NPIs might lead to the resurgence of common viruses.

Impact of COVID-19 pandemic on the prevalence of respiratory viruses in children with lower respiratory tract infections in China.

BACKGROUND: The multifaceted non-pharmaceutical interventions (NPIs) taken during the COVID-19 pandemic not only decrease the spreading of the SARS-CoV-2, but have impact on the prevalence of other viruses. This study aimed to explore the prevalence of common respiratory viruses among hospitalized children with lower respiratory tract infections (LRTI) in China during the COVID-19 pandemic. METHODS: Respiratory specimens were obtained from children with LRTI at Children's Hospital of Fudan University for detection of respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV) 1 to 3, influenza virus A (FluA), influenza virus B (FluB), human metapneumovirus (MPV) and rhinovirus (RV). The data were analyzed and compared between the year of 2020 (COVID-19 pandemic) and 2019 (before COVID-19 pandemic). RESULTS: A total of 7107 patients were enrolled, including 4600 patients in 2019 and 2507 patients in 2020. Compared with 2019, we observed an unprecedented reduction of RSV, ADV, FluA, FluB, and MPV infections in 2020, despite of reopening of schools in June, 2020. However, the RV infection was significantly increased in 2020 and a sharp increase was observed especially after reopening of schools. Besides, the PIV infection showed resurgent characteristic after September of 2020. The mixed infections were significantly less frequent in 2020 compared with the year of 2019. CONCLUSIONS: The NPIs during the COVID-19 pandemic have great impact on the prevalence of common respiratory viruses in China. Meanwhile, we do need to be cautious of a possible resurgence of some respiratory viruses as the COVID-19 restrictions are relaxed.

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.

A new accurate assay for Coxsackievirus A 16 by fluorescence detection of isothermal RNA amplification.

Coxsackievirus A 16 (CA16) is one of the most common causes of hand, foot, and mouth disease (HFMD) worldwide. Without a vaccine or antiviral drug early, rapid, and accurate detection is critical for preventing and controlling HFMD. A simultaneous amplification and testing (SAT) assay was developed for detecting CA16 based on isothermal RNA amplification with fluorescence using standard, real-time PCR equipment. Primers and probes were designed to target the VP1 region of CA16. Virus strains and clinical specimens were used to evaluate the diagnostic performance characteristics of the assay. The assay detected as few as 10 copies of CA16 RNA transcripts. Using real-time PCR plus sequencing as the reference standard, the sensitivity and specificity of the SAT-CA16 assay were 100% and 99.2%, respectively. These findings indicate that SAT-CA16 is a rapid and reliable method for detecting CA16.

[Profiles of innate immune receptors and cytokines in peripheral blood mononuclear cells in children with measles].

OBJECTIVE: The aim of this study was to explore the roles and clinical significance of innate immune receptors and cytokine in children with measles. METHOD: The children with measles hospitalized in the department of infectious diseases, Children's Hospital of Fudan University during 2009-2011 were enrolled into measles group, while the healthy children examined in well baby clinic were enrolled into control group. The mRNA expression of TLR2/3/4/7, melanoma differentiation-associated gene-5 (MDA-5), retinoic acid-inducible gene I (RIG-I), IFN-α/ß and IL-10 in peripheral blood mononuclear cells were detected by real-time PCR. The protein levels of IFN-α, IFN-ß and IL-10 in plasma were measured using ELISA. SPSS 13.0 software was applied to analyze the difference between two groups. RESULT: Data from a total of 98 patients in measles group and 59 children in control group were collected. The mRNA expressions of TLR2, MDA-5 and RIG-I had no statistical significance between two groups (P > 0.05, respectively). The relative mRNA expressions of TLR3, TLR4, TLR7 in measles group (2.25 ± 0.74, 2.05 ± 0.72, 2.12 ± 0.29) were significantly lower than those in control group (2.09 ± 0.78, 1.90 ± 0.75, 1.87 ± 0.68) (P < 0.01; respectively). Both IFN-α and IFN-ß had significantly decreased mRNA expressions in measles patients (2.41 ± 1.31, 2.47 ± 1.26) compared with those in controls (2.22 ± 0.48, 2.35 ± 0.64)(P < 0.01 respectively); however, IL-10 mRNA levels significantly increased (2.49 ± 0.58 vs. 2.62 ± 0.95) (P < 0.001). The IL-10 levels in plasma in measles group were significantly higher during the whole period of fever [<5 d group: 29.89 (25.82-38.15) ng/L and ≥ 5 d group:34.55 (28.26-38.70) ng/L] than that in control group [25.15 (24.20-27.38) ng/L] (P < 0.05 respectively). CONCLUSION: TLR3/4/7 mRNA expression was low in peripheral blood mononuclear cells of measles patients. Levels of IL-10 were significantly raised in the early stage after infection and lasted for a long time, and reduced IFN-α levels in plasma were associated with the fever durations of measles patients. These results indicated that multiple TLRs and cytokines may participate in the immune response after measles virus infection.

Novel BSCL2 gene mutation E189X in Chinese congenital generalized lipodystrophy child with early onset diabetes mellitus.

CONTEXT: Congenital generalized lipodystrophy (CGL) is a rare and heterogeneous disease of autosomal recessive inheritance. Until now, no genetic findings had been reported in Chinese patients with CGL. OBJECTIVE: To analyze Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) and 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) gene variation in a Chinese boy with CGL and his family. DESIGN, SETTING, AND PARTICIPANTS: All exons of BSCL2 and AGPAT2 with adjacent intron-exon junctions were analyzed using direct sequencing. MAIN OUTCOME MEASURES: Sequences of each exon and nearby intron of the BSCL2 and AGPAT2 genes of the family members were compared with the gene bank genomic sequences. RESULTS: DNA sequence analysis of the entire coding regions and surrounding uncoding regions disclosed a novel homozygous G-->T mutation at nucleotide 909 in exon 5 of the BSCL2 gene in the affected child. A heterozygous state of the G-->T mutation of the BSCL2 gene was also found in other family members. This mutation predicts the substitution of glutamic acid at codon 189 by the stop codon (Glu189X or E189X). No variation was found in the AGPAT2 gene. Conclusion E189X is a novel BSCL2 gene mutation that contributes to CGL formation in a family of Chinese origin.