Predominance of A2063G mutant strains in the Mycoplasma pneumoniae epidemic in children: A clinical and epidemiological study in 2023 in Wuhan, China.

OBJECTIVES: The prevalence of respiratory infectious diseases has changed in the post-COVID-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention. METHODS: Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung computed tomography imaging. RESULTS: Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild-type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MP pneumonia treatment. CONCLUSIONS: A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.

Efficacy and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia: a randomized, double-blind, placebo-controlled, multicenter clinical study.

Objective: To observe the effectiveness and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia. Methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial. Subjects who met the inclusion and exclusion criteria and were clinically diagnosed with viral pneumonia (negative for influenza virus) were randomly divided into the Lianhua Qingwen granule trial group and placebo control group. Patients in the trial group was given Lianhua Qingwen granule, 2 bags at a time, 3 times a day, and the controls were given placebo, with a treatment course of 7 days. Patients' clinical symptoms and signs, and treatment-associated adverse events were observed. Subjects should be included in the full analysis set (FAS) as long as they were all given the medication and had an effectiveness test performed after randomization. Subjects should be included in the Per Protocol Set (PPS),a subset of the total analysis set, which should contain those with strong compliance, no protocol violations, and complete baseline values for the primary indicators. Results: A total of 169 subjects were enrolled in 12 subcenters, including 151 (76 in the trial group and 75 in the control group) in the FAS and 140 (68 in the trial group and 72 in the control group) in the PPS. After 7 days of treatment, the clinical symptom relief rates were 82.98% (FAS) and 87.12% (PPS) in the trial group, and 75.11% (FAS) and 76.02% (PPS) in the control group, respectively. The clinical symptom relief rates in the trial group were significantly higher than those in the control group (p < 0.001). Significant improvements in single symptoms of cough and expectoration in the trial group were observed compared with the control group (p < 0.05). There were no statistical differences in fever, sputum color change, chest pain, muscle pain, dyspnea, chills, and thirst between the two groups (p > 0.05). Safety: There were no significant differences in body weight, vital signs, blood routine, urine routine, stool routine, and blood biochemical indicators (CK, AST, ALT, Cr, and Bun) between the two groups before and after treatment (p > 0.05). During treatment, there were no significant differences in the incidence of adverse events and serious adverse events between the two groups (p > 0.05). Conclusion: Lianhua Qingwen granules improved the clinical symptoms of patients with non-influenza virus pneumonia, especially ameliorating cough and expectoration. Lianhua Qingwen granules were associated with good safety.

Human Parvovirus B19 Nonstructural Protein 1 Regulates GATA1 Expression via the Notch Signaling Pathway in K562 Cell Line.

BACKGROUND: Human parvovirus B19 (B19) infection can affect the hematopoietic arrest in fetus by hindering the differentiation and maturation of erythroid progenitor cells. B19 nonstructural protein 1 (NS1) has been shown to inhibit the differentiation of erythroid progenitor cells. The goal of this study is to explore the role of B19 NS1 in the regulation of GATA1 and Notch signaling pathway in hematopoietic cells. METHODS: The B19 NS1 expression plasmid was reconstituted, and the possibility of NS1 regulating GATA1 and GATA2 expression modulated by Notch-Hes pathway was tested by qRT-PCR and western blot. Immunofluorescence assays were conducted to visualize pNS1 in K562 cells. RESULTS: We demonstrate that B19 NS1 inhibited GATA1 and induced Hes1/Hes5, which is involved in the activation of Notch signaling pathway. Meanwhile, NS1 exhibited promoting effects on GATA2 expression. Activation of the Notch signaling pathway up-regulated its downstream transcriptional repressor family Hes, thereby inhibiting the expression of GATA gene in K562 cells. CONCLUSIONS: The results show that B19 NS1 protein negatively regulates GATA1 related nuclear transcription and may interfere with hematopoietic cell differentiation.

Differential congenital cytomegalovirus infection in dichorionic diamniotic twins-A case report and literature review.

BACKGROUND: Cases of differential congenital cytomegalovirus (CMV) infection in twins are rarely reported. The chance of congenital infection and the clinical outcome of monochorionic diamniotic or dichorionic diamniotic twins are highly uncertain. CASES PRESENTATION: We reported a case of differential congenital CMV infection in dichorionic diamniotic twins. Despite being exposed to the same maternal environment and similar genetic background, twins reacted differently to maternal infection and presented with non-concordant infection status. The potential mechanism of discordant infection from aspects of type of chorion and placenta and immune status has been discussed through literature review. CONCLUSION: CMV infection can present as differential congenital infection in twin pregnancy, with various clinical symptoms. Fetal cellular immune function may be involved in the pathogenesis.

New Insights of Human Parvovirus B19 in Modulating Erythroid Progenitor Cell Differentiation.

Human parvovirus B19 (B19), a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. B19 cause less symptoms in healthy individuals, also cause acute and chronic anemia in immunodeficiency patients. Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram, respectively, in acute and chronic B19 infection phase, especially occurring in patients with a shortened red cell survival or with immunodeficiency. In addition, B19-infected pregnant women may cause hydrops fetalis or fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells (EPCs) mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which has been shown to inhibit the differentiation and maturation of EPCs through inducing viral DNA damage responses and cell cycle arrest. The time phase property of NS1 activity during DNA replication and conformity to transient change of hemogram are suggestive of its role in regulating differentiation of hematopoietic cells, which is not completely understood. In this review, we summarized the bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA, which play an important role in erythroid cell proliferation and differentiation, to provide a new insight of the potential mechanism of B19-induced differential inhibition of EPCs.

The immunologic status of newborns born to SARS-CoV-2-infected mothers in Wuhan, China.

BACKGROUND: Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells. OBJECTIVE: We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester. METHODS: Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns. RESULTS: None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period. CONCLUSIONS: COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.

MicroRNAs: Mediators and Therapeutic Targets to Airway Hyper Reactivity After Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the most important pathogen correlated to the first-time infant wheezing and later recurrence after its primary infection. RSV infection promotes the bronchial smooth muscle sensitivity to leukotrienes (LTs) in acute stage, causes the extensive inflammatory reaction and the aggregation of Th2-like cells during respiratory tract obstruction. Infants and young children infected with RSV exhibit an increased susceptibility to the exposure of exogenous allergens, easy to suffer from the recurrent wheezing, which prompts that the body is still in a state of inflammation or immunological bias. However, the pathological mechanism is unclear. The recent researches demonstrate that abnormal expression of non-coding microRNAs (miRNAs) can be detected from the peripheral blood and airway tract epithelial of RSV infected infants, which participate the regulation of immune cells polarization and LTs synthesis. Improving the immune tolerance can significantly relieve the airway inflammation and broncho-spasm caused by RSV. In this review, we discuss recent advances in understanding the mechanism of RSV-induced inflammatory reaction and immune dysfunction leading to airway hyper-reactivity. Further, we summarize the potential molecular basis that, in this process, miRNAs, which are produced by airway epithelial cells or peripheral blood mononuclear cells, directly or in the form of exosome to regulate the inflammation programs as well as the function, differentiation and proliferation of immune cells. miRNAs may become a potential bio-marker of detecting severe RSV infection and a novel target of early intervention and therapeutic strategy in recurrent wheezing or asthma related to RSV infection.