Differential diagnosis of precocious puberty in girls during the COVID-19 pandemic: a pilot study.

BACKGROUND: To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment. METHODS: From January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes. RESULTS: Sixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%. CONCLUSION: The prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.

Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Retro-2 alters Golgi structure.

Retro-2 directly interacts with an ER exit site protein, Sec16A, inhibiting ER exit of a Golgi tSNARE, Syntaxin5, which results in rapid re-distribution of Syntaxin5 to the ER. Recently, it was shown that SARS-CoV-2 infection disrupts the Golgi apparatus within 6-12 h, while its replication was effectively inhibited by Retro-2 in cultured human lung cells. Yet, exactly how Retro-2 may influence ultrastructure of the Golgi apparatus have not been thoroughly investigated. In this study, we characterized the effect of Retro-2 treatment on ultrastructure of the Golgi apparatus using electron microscopy and EM tomography. Our initial results on protein secretion showed that Retro-2 treatment does not significantly influence secretion of either small or large cargos. Ultra-structural study of the Golgi, however, revealed rapid accumulation of COPI-like vesicular profiles in the perinuclear area and a partial disassembly of the Golgi stack under electron microscope within 3-5 h, suggesting altered Golgi organization in these cells. Retro-2 treatment in cells depleted of GRASP65/55, the two well-known Golgi structural proteins, induced complete and rapid disassembly of the Golgi into individual cisterna. Taken together, these results suggest that Retro-2 profoundly alters Golgi structure to a much greater extent than previously anticipated.

Retro-2 Alters Golgi Structure and Function (preprint)

Retro-2 directly interacts with an ER exit site protein, Sec16A, inhibiting ER exit of a Golgi tSNARE, Syntaxin5, which results in rapid re-distribution of Syntaxin5 to the ER. Recently, it was shown that SARS-CoV-2 infection disrupts the Golgi apparatus within 6–12 hours, while its replication was effectively inhibited by Retro-2 in cultured human lung cells. Yet, exactly how Retro-2 may influence ultrastructure of the Golgi apparatus and its function have not been thoroughly investigated. In this study, we characterized the effect of Retro-2 treatment on Golgi function and its ultrastructure using electron microscopy and EM tomography. Our results indicate that Retro-2 treatment significantly alters protein glycosylation at the Golgi without affecting secretion of either small or large cargos. Ultra-structural study of the Golgi revealed rapid accumulation of COPI-like vesicular profiles in the perinuclear area and a partial disassembly of the Golgi stack under electron microscope within 3–5 hours, suggesting altered Golgi organization in these cells. Retro-2 treatment in cells depleted of GRASP65/55, the two well-known Golgi stacking proteins, induced complete and rapid disassembly of the Golgi into individual cisterna. Taken together, these results suggest that Retro-2 profoundly alters Golgi structure and function to a much greater extent than previously anticipated.

Persistence of SARS-CoV-2 RNA in wastewater after the end of the COVID-19 epidemics.

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely detected in wastewater in many countries to track the COVID-19 pandemic development, it is still a lack of clear understanding of the persistence of SARS-CoV-2 in raw sewage, especially after the end of the COVID-19 pandemic event. To fill this knowledge gap, this study conducted a field trial on the SARS-CoV-2 presence in various wastewater facilities after the end of the COVID-19 epidemics in Beijing. The result showed that the wastewater treatment facility is a large SARS-CoV-2 repository. The viral RNA was still present in hospital sewage for 15 days and was continually detected in municipal WWTPs for more than 19 days after the end of the local COVID-19 epidemics. The T90 values of the SARS-CoV-2 RNA in raw wastewater were 17.17-8.42 days in the wastewater at 4 â„ƒ and 26 â„ƒ, respectively, meaning that the decay rates of low titer viruses in raw sewage were much faster. The results confirmed that the SARS-CoV-2 RNA could persist in wastewater for more than two weeks, especially at lower temperatures. The sewage systems would be a virus repository and prolong the presence of the residual SARS-CoV-2 RNA. The study could enhance further understanding of the presence of SARS-CoV-2 RNA in raw wastewater.

Tailoring glucocorticoids in patients with severe COVID-19: a narrative review.

OBJECTIVE: To discuss the pathogenesis of severe coronavirus disease 2019 (COVID-19) infection and the pharmacological effects of glucocorticoids (GCs) toward this infection. To review randomized controlled trials (RCTs) using GCs to treat patients with severe COVID-19, and investigate whether GC timing, dosage, or duration affect clinical outcomes. Finally. to discuss the use of biological markers, respiratory parameters, and radiological evidence to select patients for improved GC therapeutic precision. BACKGROUND: COVID-19 has become an unprecedented global challenge. As GCs have been used as key immunomodulators to treat inflammation-related diseases, they may play key roles in limiting disease progression by modulating immune responses, cytokine production, and endothelial function in patients with severe COVID-19, who often experience excessive cytokine production and endothelial and renin-angiotensin system (RAS) dysfunction. Current clinical trials have partially proven this efficacy, but GC timing, dosage, and duration vary greatly, with no unifying consensus, thereby creating confusion. METHODS: Publications through March 2021 were retrieved from the Web of Science and PubMed. Results from cited references in published articles were also included. CONCLUSIONS: GCs play key roles in treating severe COVID-19 infections. Pharmacologically, GCs could modulate immune cells, reduce cytokine and chemokine, and improve endothelial functions in patients with severe COVID-19. Benefits of GCs have been observed in multiple clinical trials, but the timing, dosage and duration vary across studies. Tapering as an option is not widely accepted. However, early initiation of treatment, a tailored dosage with appropriate tapering may be of particular importance, but evidence is inconclusive and more investigations are needed. Biological markers, respiratory parameters, and radiological evidence could also help select patients for specific tailored treatments.

Factors Associated with the Acceptance and Willingness of COVID-19 Vaccination among Chinese Healthcare Workers (preprint)

Background: Vaccination is a crucial measure in preventing the spread of epidemic. Vaccines targeting coronavirus disease 2019 (COVID-19) have been developed in a wide range of countries. Objective: This study aims to examine factors influencing vaccination rate and willingness to vaccinate against COVID-19 among Chinese healthcare workers (HCWs). Methods: From 3rd February to 18th February, 2021, an online cross-sectional survey was conducted among HCWs to investigate factors associated with the acceptance and willingness of COVID-19 vaccination. Respondents were classified into two categories, vaccinated and unvaccinated, and, the willingness of vaccination was assessed in the unvaccinated group. Information on socio-demographics and the psychological process of the participants for accepting the vaccine were evaluated. Results: A total of 2156 HCWs from 21 provinces in China responded to this survey (response rate: 98.99%)), among whom 1433 (66.5%) were vaccinated at least one dose. Higher vaccination rates were associated with older age (40-50 years vs. less than 30 years, OR=1.63, 95%CI: 1.02-2.58; >50 years vs. 30 years, OR=1.90, 95%CI: 1.02-3.52), working as a clinician (OR=1.54, 95% CI: 1.05-2.27), having no personal religion (OR=1.35, 95%CI: 1.06-1.71), working in a fever clinic (OR=4.50 , 95%CI:1.54-13.17) or higher hospital level(Municipal vs. County, OR=2.01, 95%CI: 1.28-3.16; Provincial vs. County, OR=2.01, 95%CI: 1.25-3.22) and having knowledge training of vaccine (OR=1.67, 95%CI:1.27-2.22), family history for influenza vaccination (OR=1.887, 95%CI:1.49-2.35) and strong familiarity with the vaccine (OR=1.43, 95%CI:1.05-1.95) (All P<0.05). Strong willingness for vaccination was related to having a working in midwestern China (OR=1.89, 95%CI:1.24-2.89), considerable knowledge of the vaccine (familiar vs. not familiar, OR=1.67, 95%CI: 1.17-2.39; strongly familiar vs. not familiar, OR=2.47, 95%CI: 1.36-4.49), knowledge training of vaccine(OR=1.61, 95%CI: 1.05-2.48) and strong confidence in the vaccine (OR=3.84 , 95%CI: 2.09-7.07). Conclusion: Personal characteristics, working environments, familiarity and confidence in the vaccine were related to vaccination rates and willingness to get vaccinated among healthcare workers. Results of this study could provide evidence for the government to improve vaccine coverage by addressing vaccine hesitancy in the COVID-19 pandemic and future public health emergencies.

Prevalence and Risk Factors Associated With Self-reported Psychological Distress Among Children and Adolescents During the COVID-19 Pandemic in China.

Importance: Schools have been suspended nationwide in 188 countries, and classes have shifted to home-based distance learning models to control the spread of the coronavirus disease 2019 (COVID-19) pandemic. Additional information is needed to determine mental health status among school-aged children and adolescents during this public health crisis and the risk factors associated with psychological distress during the pandemic. Objective: To assess self-reported psychological distress among school-aged children and adolescents associated with the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study using data from a survey on the mental health of school-aged children and adolescents in Guangdong province, China, conducted by using a stratified cluster random sampling method between March 8 to 30, 2020. To estimate outcomes associated with location of districts, only data from students with internet protocol addresses and current addresses in Guangdong were included. Data were analyzed from April 5 to July 20, 2020. Exposure: Home-based distance learning during the COVID-19 pandemic. Main Outcome and Measures: The main outcome was self-reported psychological distress, measured using the total score on the 12-item General Health Questionnaire of 3 or greater. Multivariate logistic regression was used to analyze risk factors associated with mental health status. Odds ratios (ORs) were used to analyze the associations of factors with psychological distress. Results: Among 1 310 600 students who completed the survey, 1 199 320 students (mean [SD] age, 12.04 [3.01] years; 619 144 [51.6%] boys) were included in the final analysis. A total of 126 355 students (10.5%) self-reported psychological distress. Compared with students in primary school, high school students had increased risk of psychological distress (OR, 1.19 [95% CI, 1.15-1.23]). Compared with students who wore a face mask frequently, students who never wore a face mask had increased risk of psychological distress (OR, 2.59 [95% CI, 2.41-2.79]). Additionally, students who spent less than 0.5 hours exercising had increased odds of self-reported psychological distress compared with students who spent more than 1 hour exercising (OR, 1.64 [95% CI, 1.61-1.67]). Conclusions and Relevance: These findings suggest that the prevalence of self-reported psychological distress among students during the COVID-19 pandemic was relatively high. Frequency of wearing a face mask and time spent exercising were factors associated with mental health. Therefore, it may be necessary for governments, schools, and families to pay attention to the mental health of school-aged children and adolescents during the COVID-19 pandemic and take corresponding countermeasures to reduce the impact of the COVID-19 pandemic on students' mental health.

Primary Care Practitioners' Barriers to and Experience of COVID-19 Epidemic Control in China: a Qualitative Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) emerged in December 2019 and posed numerous challenges to China's health system. Almost 4 million primary care practitioners (PCPs) participated in controlling the outbreak. However, PCPs' barriers to and experience of the epidemic control remain unknown and are essential for improving countermeasures. OBJECTIVE: To better understand the barriers PCPs faced in COVID-19 epidemic control and their psychological and occupational impacts, and explore potential solutions. DESIGN: This qualitative study was conducted through semi-structured, in-depth interviews from February 12, to March 10, 2020. PARTICIPANTS: A purposive sample of frontline PCPs affiliated with either community health centers or township health centers in four provinces of China were recruited. APPROACH: Interviews were conducted by telephone, and then recorded, transcribed, and content analyzed. Themes surrounding PCPs' barriers to COVID-19 epidemic control, their experience, and potential solutions were iteratively identified using the constant comparative method. KEY RESULTS: Of the 21 PCPs interviewed, 10 (48%) were women and 5 (24%) worked in rural areas. Barriers to epidemic control in primary care included inappropriate PCP scheduling and role ambiguity, difficult tasks and inadequate capacities, and inexperienced community workers and insufficient cooperation. Some PCPs perceived respect and a sense of accomplishment and were preoccupied with the outbreak, while others were frustrated by fatigue and psychological distress. PCPs reported potential solutions for improving countermeasures, such as improving management, optimizing workflows, providing additional support, facilitating cooperation, and strengthening the primary care system. CONCLUSIONS: Due to their roles in controlling the COVID-19 epidemic, PCPs in China faced a series of barriers that affected them physically and mentally. Support for PCPs should help them to overcome these barriers and work efficiently. The current findings provide insight into the challenges and potential solutions for strengthening the preparedness and response of China's primary care system in future disease outbreaks.