Genetic and Clinical Profiles of Disseminated Bacillus Calmette-Guérin Disease and Chronic Granulomatous Disease in China

Background: Disseminated Bacillus Calmette-Guérin disease (D-BCG) in children with chronic granulomatous disease (CGD) can be fatal, while its clinical characteristics remain unclear because both diseases are extremely rare. The patients with CGD receive BCG vaccination, because BCG vaccination is usually performed within 24 h after delivery in China.Methods: We prospectively followed-up Chinese patients with CGD who developed D-BCG to characterize their clinical and genetic characteristics. The diagnoses were based on the patients' clinical, genetic, and microbiological characteristics.Results: Between September 2009 and September 2016, we identified 23 patients with CGD who developed D-BCG. Their overall 10-year survival rate was 34%. We created a simple dissemination score to evaluate the number of infected organ systems and the survival probabilities after 8 years were 62 and 17% among patients with simple dissemination scores of ≤3 and >3, respectively (p = 0.0424). Survival was not significantly associated with the CGD stimulation index or interferon-γ treatment. Eight patients underwent umbilical cord blood transplantation and 5 of them were successfully treated. The genetic analyses found mutations in CYBB (19 patients), CYBA (1 patient), NCF1 (1 patient), and NCF2 (1 patient). We identified 6 novel highly likely pathogenic mutations, including 4 mutations in CYBB and 2 mutations in NCF1.Conclusions: D-BCG is a deadly complication of CGD. The extent of BCG spreading is strongly associated with clinical outcomes, and hematopoietic stem cell transplantation may be a therapeutic option for this condition

Impact of Tuberculosis on Disease Severity and Viral Shedding Duration in COVID-19 Patients

Accumulating evidence show a potential association between tuberculosis and COVID-19 disease severity. To further clarify the impact of tuberculosis on COVID-19 disease severity and viral shedding duration, a retrospective study was conducted on 223 COVID-19 patients, including 34 with tuberculosis and 189 without tuberculosis. Clinical information and viral load shedding time were collected. A higher percentage of severe/critical COVID-19 diagnosis and deaths was observed in patients with tuberculosis than in those without tuberculosis (8.8% vs. 3.2%, p = 0.142; 2.9% vs. 1.1%, p = 0.393), and COVID-19 patients with tuberculosis had longer viral shedding than those without tuberculosis (median: 15.0 days vs. 11.0 days; p = 0.0001). Having tuberculosis (HR = 2.21, 95% CI 1.37–3.00; p = 0.000), being of elderly age (HR = 1.02, 95% CI 1.01–1.03; p = 0.001) and being diagnosed with severe or critical COVID-19 (HR = 5.63, 95% CI 2.10–15.05; p = 0.001) were independent factors associated with prolonged virus time of SARS-CoV-2. COVID-19 patients with tuberculosis receiving anti-tuberculosis therapy time (ATT) for p = 0.012). Our results demonstrated that COVID-19 patients with tuberculosis tend to have more severe disease and a worse prognosis, and tuberculosis prolonged viral shedding, highlighting special attention and/or care required for COVID-19 patients with tuberculosis receiving ATT for <2 months

Association of Breastfeeding for the First Six Months of Life and Autism Spectrum Disorders: A National Multi-Center Study in China

Previous studies have shown that exclusive breastfeeding is associated with lower odds of having autism spectrum disorders (ASD) in children, but data are lacking in Asian countries, especially China. This cross-sectional study of seven cities in China collected data from August 2016 to March 2017 from 6049 toddlers aged 16–30 months and their parents who responded to questionnaires. The breastfeeding status was collected via questionnaires based on recommendations from the World Health Organization. The standard procedure for screening and diagnosis was applied to identify toddlers with ASD. Among the 6049 toddlers (3364 boys [55.6%]; mean [SD] age, 22.7 [4.1] months), 71 toddlers (1.2%) were identified as ASD. The prevalence of exclusive breastfeeding, partial breastfeeding, and not breastfeeding was 48.8%, 42.2%, and 9.1%, respectively. Compared to toddlers with exclusive breastfeeding, toddlers with partial breastfeeding or without breastfeeding had higher odds of having ASD (odd ratios [OR]: 1.55, 95% confidence interval [CI]: 0.90–2.74; OR: 2.34, 95% CI: 1.10–4.82). We did not find significant modification of demographic characteristics on the associations. The results remained robust in multiple sensitivity analyses. Toddlers without breastfeeding for the first six months of life had higher odds of having ASD, and our findings shed light on the necessity of strengthening public health efforts to increase exclusive breastfeeding in China

Clinical Comparison of One Recovered Case and One Fatal Case of Human Infection with H7N9 Avian Influenza in Shanghai Public Health Clinical Center in China

H7N9 avian influenza is the latest subtype of influenza virus to emerge in the world. By April 17, 2013 in Shanghai, a total of 31 confirmed cases were reported, and 11 of these patients died. The epidemiological characteristics and the clinical progress of this new human flu infection are still not clear. Thirteen confirmed patients have now been treated in Shanghai Public Health Clinical Center. Among the first batch of patients, hospitalised at the beginning of April 2013, two who were admitted with the same estimated date of onset of disease had very different outcomes. After active treatment at the Centre, one recovered by April 18, 2013, but one patient entered critical condition and died on April 11, 2013. The clinical and laboratory characteristics in hospital are here analysed and compared to learn more about H7N9 avian influenza. Confirmation that the observed differences are valuable for prognosis and treatment decisions for H7N9 patients awaits authentication by analysis of more patients

Clinical Findings for Early Human Cases of Influenza A(H7N9) Virus Infection, Shanghai, China

A novel strain of influenza A(H7N9) virus has emerged in China and is causing mild to severe clinical symptoms in infected humans. Some case-patients have died. To further knowledge of this virus, we report the characteristics and clinical histories of 4 early case-patients

Early hypercytokinemia is associated with interferoninduced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection

A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced “cytokine storm” at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia

Prognosis of 18 H7N9 avian influenza patients in Shanghai.

To provide prognosis of an 18 patient cohort who were confirmed to have H7N9 lung infection in Shanghai.Patients' history, clinical manifestation, laboratory test, treatment strategy and mortality were followed and recorded for data analysis.A total of 18 patients had been admitted into Shanghai Public Health Clinical Center from April 8th to July 29, 2013. 22.2% of the patients were found to have live poultry contact history and 80% were aged male patients with multiple co-morbidities including diabetes, hypertension and/or chronic obstructive pulmonary disease (COPD). This group of patients was admitted to the clinical center around 10 days after disease onset. According to laboratory examinations, increased C reactive protein (CRP), Procalcitonin (PCT), Plasma thromboplastin antecedent (PTA) and virus positive time (days) were indicative of patients' mortality. After multivariate analysis, only CRP level showed significant prediction of mortality (P = 0.013) while results of prothrombin time (PT) analysis almost reached statistical significance (P = 0.056).H7N9 infection induced pneumonia of different severity ranging from mild to severe pneumonia or acute lung injury/acute respiratory distress syndrome to multiple organ failure. Certain laboratory parameters such as plasma CRP, PCT, PTA and virus positive days predicted mortality of H7N9 infection and plasma CRP is an independent predictor of mortality in these patients