Intra- vs. Interhost Evolution of SARS-CoV-2 Driven by Uncorrelated Selection-The Evolution Thwarted.

In viral evolution, a new mutation has to proliferate within the host (Stage I) in order to be transmitted and then compete in the host population (Stage II). We now analyze the intrahost single nucleotide variants (iSNVs) in a set of 79 SARS-CoV-2 infected patients with most transmissions tracked. Here, every mutation has two measures: 1) iSNV frequency within each individual host in Stage I; 2) occurrence among individuals ranging from 1 (private), 2-78 (public), to 79 (global) occurrences in Stage II. In Stage I, a small fraction of nonsynonymous iSNVs are sufficiently advantageous to rise to a high frequency, often 100%. However, such iSNVs usually fail to become public mutations. Thus, the selective forces in the two stages of evolution are uncorrelated and, possibly, antagonistic. For that reason, successful mutants, including many variants of concern, have to avoid being eliminated in Stage I when they first emerge. As a result, they may not have the transmission advantage to outcompete the dominant strains and, hence, are rare in the host population. Few of them could manage to slowly accumulate advantageous mutations to compete in Stage II. When they do, they would appear suddenly as in each of the six successive waves of SARS-CoV-2 strains. In conclusion, Stage I evolution, the gate-keeper, may contravene the long-term viral evolution and should be heeded in viral studies.

High titers of neutralizing antibodies in the blood fail to eliminate SARS-CoV-2 viral RNA in the upper respiratory tract.

Retest-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA, as a unique phenomenon among discharged individuals, has been demonstrated to be safe in the community. Still, the underlying mechanism of viral lingering is less investigated. In this study, first, we find that the frequency of viral RNA-positive retesting differs among variants. Higher ratios of viral RNA-positive retest were more frequently observed among Delta (61.41%, 514 of 837 cases) and Omicron (39.53%, 119 of 301 cases) infections than among ancestral viral infection (7.27%, 21 of 289 cases). Second, the tissues where viral RNA reoccurred were altered. Delta RNA reoccurred mainly in the upper respiratory tract (90%), but ancestral virus RNA reoccurred mainly in the gastrointestinal tract (71%). Third, vaccination did not reduce the frequency of viral RNA-positive retests, despite high concentrations of viral-specific antibodies in the blood. Finally, 37 of 55 (67.27%) Delta-infected patients receiving neutralizing antibody therapy become viral RNA retest positive when high concentrations of neutralizing antibodies still patrol in the blood. Altogether, our findings suggest that the presentence of high titers of neutralizing antibodies in the blood is incompetent in clearing residual viral RNA in the upper respiratory tract.

Perioperative Albumin Supplementation is Associated With Decreased Risk of Complications Following Microvascular Head and Neck Reconstruction.

PURPOSE: Studies have demonstrated that low serum albumin levels are associated with a high postoperative complication rate after microvascular free flap reconstruction. The aim of this study was to investigate whether perioperative albumin supplementation reduced the postoperative complications of microvascular free flap reconstruction in oral and maxillofacial tumor resections. PATIENTS AND METHODS: Patients who underwent microvascular free flap reconstruction during oral and maxillofacial tumor resections from January 2012 to December 2017 were enrolled in this retrospective study. The predictor variable was perioperative albumin supplementation. The primary outcome variables were surgery-associated postoperative complications, including local and systemic complications. The secondary outcome variables were the total duration of hospital stay, postoperative ICU admission rate, duration of ICU stay, and mortality during hospitalization. RESULTS: In total, 315 patients met the criteria. Patients with serum albumin supplementation showed a lower rate of surgery-associated local complications (6.5 vs 21.6%) with an adjusted odds ratio (OR) of 0.24 (95% confidence interval (CI), 0.12 to 0.49, P < .001). The average postoperative hospital stay was significantly shortened for patients with albumin supplementation (12.56 ± 4.23 vs 15.34 ± 5.24 days, P < .001). However, albumin supplementation had no effect on systemic complications. CONCLUSIONS: The results of this study suggest that perioperative albumin supplementation is associated with a decreased risk of local complications, shortened hospital stay, and decreased need for crystalloid infusion in patients who underwent oral and maxillofacial tumor resections with microvascular free flap reconstruction.

Evaluation of the effectiveness of a WHO-5A model based comprehensive tobacco control program among migrant workers in Guangdong, China: a pilot study.

BACKGROUND: As a vulnerable population in China, migrant workers have a higher smoking rate than the general population. This study aims to assess the effectiveness of a WHO-5A based comprehensive tobacco control program in workplaces aggregated with migrants. METHODS: Using a controlled before and after design, four purposely selected manufacturing factories were assigned to either intervention or control groups. Participants in the intervention arm received adapted 5A group counseling regularly supported by social-media and traditional health education approaches. The primary outcome was the change of smoking rate based on salivary cotinine concentration at three-month follow-up as compared to the control arm. Secondary outcomes were changes in smoking-related knowledge and attitudes assessed using questionnaires. Difference-in-differences approach (DID) and generalized estimating equations (GEE) models were used to conduct the effectiveness analysis. RESULTS: 149 and 166 workers were enrolled in the intervention and control arm respectively. The multiple imputed and adjusted GEE models demonstrated that, compared to those in the control arm, participants in the intervention arm had nearly 2.4 times odds of improving smoking-related knowledge (OR = 2.40, 95% CI = 1.32-4.36, P = 0.02) and three times the odds of improving smoking-related attitude (OR = 3.07, 95% CI = 1.28-7.41, P = 0.03). However, no significant difference was found regarding the change of smoking rate between the two arms (P > 0.05). The regression analysis showed that attendance at the 5A group counseling sections was an important determinant of stopping smoking or improving smoking-related knowledge and attitudes in the intervention group. CONCLUSIONS: This WHO-5A comprehensive intervention was effective in improving migrant workers' knowledge of smoking and anti-smoking attitudes. A large-scale, long-term trial is recommended to determine the effectiveness of this intervention. TRIAL REGISTRATION: ChiCTR-OPC-17011637 at Chinese Clinical Trial Registry. Retrospectively registered on 12th June 2017.

Study protocol: a cluster randomized controlled trial to assess the effectiveness of a multi-pronged behavioural intervention to improve use of personal protective equipment among migrant workers exposed to organic solvents in small and medium-sized enterprises.

BACKGROUND: In China, most of migrant workers work in the small and medium-sized enterprises (SMEs) and are a vulnerable group for occupational health. Migrant workers are at increased risk of occupational health risks due to poor occupational health behaviours such as the low use of personal protective equipment (PPE). However, there is a lack of solid evidence regarding how to improve the use of PPE among migrant workers in SMEs. The current study will assess the effectiveness of a multi-pronged behavioural intervention designed to promote PPE utilization among migrant workers exposed to organic solvents in SMEs. METHODS/DESIGN: This is a single blind, three-arm cluster randomized trial with 60 SMEs equally randomized to receive a top-down intervention (i.e. general health education and mHealth intervention provided by researchers) or a comprehensive intervention (which includes both top-down intervention and peer education) or a control condition (participants will not receive the intervention, but study measures will be obtained). Interventions will be conducted at the SMEs level for 6 months and all eligible migrant workers in these SMEs will be enrolled into the trial. The primary outcome is effective use of PPE during the last week. The secondary outcomes are occupational health knowledge and attitude and participation in occupational health check-up. Data will be collected and assessed at baseline; 3 months post baseline and the end of the intervention. DISCUSSION: This theory- and evidence based intervention will contribute to the limited evidence of behaviour change intervention in improving PPE utilization of migrant workers in SMEs, and provide timely evidence for the development of basic occupational health services in China and elsewhere with similar industrialization contexts. TRIAL REGISTRATION: ChiCTR-IOR-15006929 . Registered on 16 August 2015.

[Analysis of use of personal protective equipment among rural-to-urban migrant workers in small and medium enterprises in Zhongshan and Shenzhen, China].

OBJECTIVE: To investigate the current supply and use of personal protective equipment (PPE) among rural-to-urban migrant workers in small and medium enterprises (SMEs) in Zhongshan and Shenzhen, China and the influential factors for the use of PPE, and to provide a basis for better occupational health services and ensuring the health of migrant workers. METHODS: Multi-stage sampling was used to select 856 migrant workers from 27 SMEs in Zhongshan and Shenzhen, and face-to-face questionnaire survey was conducted in these subjects. Statistical analysis was performed by one-way analysis of variance, chi-square test, and logistic regression. RESULTS: Of all migrant workers, 38.67%were supplied with free PPE by the factory, and this rate varied across industries (furniture industry: 45.81%; electronic industry: 31.46%) and SMEs (medium enterprises: 42.13%; small enterprises: 39.20%; micro enterprises: 22.16%); 22.43% insisted on the use of PPE. The logistic regression analysis showed that factors associated with the use of PPE included sex, age, awareness of occupational health knowledge, and the size of enterprise. CONCLUSION: The rates of supply and use of PPE among migrant workers are low. The larger the enterprise, the better the supply of PPE. Male gender, being elder, and high occupational health knowledge score were favorable factors for the use of PPE, while small enterprise size was the unfavorable factor for the use of PPE.

Interferon stimulated immune profile changes in a humanized mouse model of HBV infection.

The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.

Immune response and severity of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants.

Introduction: COVID-19 continues to spread worldwide, with an increasing number of individuals experiencing reinfection after recovering from their primary infection. However, the nature and progression of this infection remain poorly understood. We aimed to investigate the immune response, severity and outcomes of Omicron BA.5 reinfection among individuals previously infected with different SARS-CoV-2 variants. Methods: We enrolled 432 COVID-19 cases who had experienced prior infection with the ancestral SARS-CoV-2 virus, Delta variant or Omicron BA.2 variant between January 2020 and May 2022 in Guangzhou, China. All cases underwent follow-up from March to April, 2023 through telephone questionnaires and clinical visits. Nasal lavage fluid and peripheral blood were collected to assess anti-RBD IgA, anti-RBD IgG and virus-specific IFN-γ secreting T cells. Results: Our study shows that 73.1%, 56.7% and 12.5% of individuals with a prior infection of the ancestral virus, Delta or Omicron BA.2 variant experienced reinfection with the BA.5 variant, respectively. Fever, cough and sore throat were the most common symptoms of BA.5 reinfection, with most improving within one week and none progressing to a critical condition. Compared with individuals without reinfection, reinfected patients with a prior Delta infection exhibited elevated levels of nasal anti-RBD IgA, serum anti-RBD IgG and IFN-γ secreting T cells, whereas there was no noticeable change in reinfected individuals with a prior BA.2 infection. Conclusion: These results suggest that BA.5 reinfection is common but severe outcomes are relatively rare. Reinfection with a novel SARS-CoV-2 variant different from the prior infection may induce a more robust immune protection, which should be taken into account during vaccine development.

Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants.

SARS-CoV-2 Omicron variants feature highly mutated spike proteins with extraordinary abilities in evading antibodies isolated earlier in the pandemic. Investigation of memory B cells from patients primarily with breakthrough infections with the Delta variant enables isolation of a number of neutralizing antibodies cross-reactive to heterologous variants of concern (VOCs) including Omicron variants (BA.1-BA.4). Structural studies identify altered complementarity determining region (CDR) amino acids and highly unusual heavy chain CDR2 insertions respectively in two representative cross-neutralizing antibodies-YB9-258 and YB13-292. These features are putatively introduced by somatic hypermutation and they are heavily involved in epitope recognition to broaden neutralization breadth. Previously, insertions/deletions were rarely reported for antiviral antibodies except for those induced by HIV-1 chronic infections. These data provide molecular mechanisms for cross-neutralization of heterologous SARS-CoV-2 variants by antibodies isolated from Delta variant infected patients with implications for future vaccination strategy.

Predictive mutation signature of immunotherapy benefits in NSCLC based on machine learning algorithms.

Background: Developing prediction tools for immunotherapy approaches is a clinically important and rapidly emerging field. The routinely used prediction biomarker is inaccurate and may not adequately utilize large amounts of medical data. Machine learning is a promising way to predict the benefit of immunotherapy from individual data by individuating the most important features from genomic data and clinical characteristics. Methods: Machine learning was applied to identify a list of candidate genes that may predict immunotherapy benefits using data from the published cohort of 853 patients with NSCLC. We used XGBoost to capture nonlinear relations among many mutation genes and ICI benefits. The value of the derived machine learning-based mutation signature (ML-signature) on immunotherapy efficacy was evaluated and compared with the tumor mutational burden (TMB) and other clinical characteristics. The predictive power of ML-signature was also evaluated in independent cohorts of patients with NSCLC treated with ICI. Results: We constructed the ML-signature based on 429 (training/validation = 8/2) patients who received immunotherapy and extracted 88 eligible predictive genes. Additionally, we conducted internal and external validation with the utility of the OAK+POPLAR dataset and independent cohorts, respectively. This ML-signature showed the enrichment in immune-related signaling pathways and compared to TMB, ML-signature was equipped with favorable predictive value and stratification. Conclusion: Previous studies proposed no predictive difference between original TMB and modified TMB, and original TMB contains some genes with no predictive value. To demonstrate that fewer genetic tests are sufficient to predict immunotherapy efficacy, we used machine learning to screen out gene panels, which are used to calculate TMB. Therefore, we obtained the 88-gene panel, which showed the favorable prediction performance and stratification effect compared to the original TMB.

Selection and validation of chemotherapy beneficiaries among elderly nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT): a large real-world study.

PURPOSE: Using real-world evidence, this study aimed to identify elderly nasopharyngeal carcinoma (NPC) patients who would benefit from chemotherapy. METHODS AND MATERIALS: 1714 elderly NPC patients between April 2007 and December 2017 were identified. Recursive partitioning analysis (RPA) was used to generate risk-stratified outcomes. Prognostic factors were performed for individual comparisons of different risk groups to assess chemotherapy benefits. RESULTS: The median follow-up was 59.3 (0.39-170.09) months. Epstein Barr virus (EBV) DNA and T stage were included in the RPA-generated risk stratification, categorizing patients into a good-prognosis group (EBV DNA ≤ 4000 copies/mL & T1-2), and a poor-prognosis group (EBV DNA ≤ 4000 copies/mL & T3-4 and EBV DNA > 4000 copies/mL & any T). Overall survival (OS) was significantly higher in the good-prognosis group compared with the training set (HR = 0.309, 95% CI 0.184-0.517; P < 0.001), and validated in the testing set (HR = 0.276, 95% CI 0.113-0.670; P = 0.002). In the poor-prognosis group, a significantly improved OS for chemoradiotherapy (CRT) compared with RT alone was observed (HR = 0.70, 95% CI 0.55-0.88; P = 0.003). Patients who received induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) and CCRT had a significantly improved OS compared with RT alone (IC + CCRT vs. RT alone: P = 0.002; CCRT vs. RT alone: P = 0.008) but not in the IC + RT group (P = 0.306). The 5-year OS for CRT versus RT-alone with ACE-27 scores of 0, 1 and 2 were 76.0% versus 70.0% (P = 0.014), 80.5% versus 68.2% (P = 0.150) and 58.5% versus 62.2% (P = 0.490), respectively; for those aged 60-64, 65-70 and ≥ 70 years old they were 80.9% versus 75.9% (P = 0.068), 73.3% versus 63.4% (P = 0.270) and 64.8% versus 67.1% (P = 0.820), respectively. CONCLUSIONS: For elderly NPC patients a simple screening cutoff for chemotherapy beneficiaries might be EBV DNA < 4000 copies/ml & T3-4 and EBV DNA ≥ 4000 copies/ml & any T, but not for those > 70 years old and with an ACE-27 score > 1. IC + CCRT and CCRT were effective forms of chemotherapy.

Long-Term Evaluation and Normal Tissue Complication Probability (NTCP) Models for Predicting Radiation-Induced Optic Neuropathy after Intensity-Modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma: A Large Retrospective Study in China.

PURPOSE: To quantify the long-term evaluation of optic chiasma (OC) and/or optic nerve(s) (ONs) and to develop predictive models for radiation-induced optic neuropathy (RION) in nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 3,662 patients' OC/ONs with full visual acuity and dosimetry data between 2010 and 2015 were identified. Critical dosimetry predictors of RION were chosen by machine learning and penalized regression for survival. A nomogram containing dosimetry and clinical variables was generated for predicting RION-free survival. RESULTS: The median follow-up was 71.79 (2.63-120.9) months. Sixty-six eyes in 51 patients (1.39%) developed RION. Two patients were visual field deficient, and 49 patients had visual acuity of less than 0.1 (20/200). The median latency time was 36 (3-90) months. The 3-, 5-, and 8-year cumulative incidence of RION was 0.78%, 1.19%, and 1.97%, respectively. Dmax was the most critical dosimetry variable for RION (AUC: 0.9434, the optimal cutoff: 64.48 Gy). Patients with a Dmax ≥64.48 Gy had a significantly higher risk of RION (HR = 102.25; 95%CI, 24.86-420.59; P < 0.001). Age (>44 years) (HR = 2.234, 95% CI = 1.233-4.051, p = 0.008), advanced T stage (T3 vs. T1-2: HR = 7.516, 95% CI = 1.725-32.767, p=0.007; T4 vs. T1-2: HR = 37.189, 95% CI = 8.796-157.266, P < 0.001), and tumor infiltration/compression of the OC/ONs (HR = 4.572, 95% CI = 1.316-15.874, p=0.017) were significant clinical risk factors of RION. A nomogram comprising age, T stage, tumor infiltration/compression of the OC/ON, and Dmax significantly outperformed the model, with only Dmax predicting RION (C-index: 0.916 vs. 0.880, P < 0.001 in the training set; 0.899 vs. 0.874, P=0.038 in the test set). The nomogram-defined high-risk group had a worse 8-year RION-free survival. CONCLUSIONS: In the IMRT era, Dmax <60 Gy is safe and represents an acceptable dose constraint for most NPC patients receiving IMRT. A reasonable trade-off for selected patients with unsatisfactory tumor coverage due to proximity to the optic apparatus would be Dmax <65 Gy. Caution should be exercised when treating elderly and advanced T-stage patients or those with tumor infiltration/compression of the OC/ON. Our nomogram shows strong efficacy in predicting RION.

Clinical characteristics and immune profile alterations in vaccinated individuals with breakthrough Delta SARS-CoV-2 infections.

Despite timely immunization programs, and efficacious vaccines conveying protection against SARS-CoV-2 infection, breakthrough infections in vaccinated individuals have been reported. The Delta variant of concern (VOC) outbreak in Guangzhou resulted in local transmission in vaccinated and non-vaccinated residents, providing a unique opportunity to study the protective effects of the inactivated vaccines in breakthrough infection. Here, we find that the 2-dose vaccinated group has similar peak viral titers and comparable speeds of viral RNA clearance to the non-vaccinated group but accelerated viral suppression in the middle course of the disease. We quantitatively demonstrate that peak viral pneumonia is significantly mitigated in the 2-dose vaccine group (median 0.298%) compared with the non-vaccinated (5.77%) and 1-dose vaccine (3.34%) groups. Pneumonia absorbance is approximately 6 days ahead in the 2-dose group (median 10 days) than in the non-vaccinated group (16 days) (p = 0.003). We also observe reduced cytokine inflammation and markedly undisturbed gene transcription profiles of peripheral blood mononuclear cells (PBMCs) in the 2-dose group. In short, our study demonstrates that prior vaccination substantially restrains pneumonia development, reduces cytokine storms, and facilitates clinical recovery.

Small intestinal flora graft alters fecal flora, stool, cytokines and mood status in healthy mice.

Fecal microbiota transplantation is widely used. Large intestinal microbiota (LIM) is more similar to fecal microbiota than small intestinal microbiota (SIM). The SIM communities are very different from those of LIM. Therefore, SIM transplantation (SIMT) and LIM transplantation (LIMT) might exert different influences. Here, healthy adult male C57Bl/6 mice received intragastric SIMT, LIMT, or sterile PBS administration. Microbiota graft samples were collected from small/large intestine of healthy mice of the same age, sex, and strain background. Compared with PBS treatment, SIMT increased pellet number, stool wet weight, and stool water percentage; induced a fecal microbiota profile shift toward the microbial composition of the SIM graft; induced a systemic anti-inflammatory cytokines profile; and ameliorated depressive-like behaviors in recipients. LIMT, however, induced merely a slight alteration in fecal microbial composition and no significant influence on the other aspects. In sum, SIMT, rather than LIMT, affected defecation features, fecal microbial composition, cytokines profile, and depressive-like behaviors in healthy mice. This study reveals the different effects of SIMT and LIMT, providing an interesting clue for further researches involving gut microbial composition change.

Trends of pulmonary fungal infections from 2013 to 2019: an AI-based real-world observational study in Guangzhou, China.

Recently, the prevalence trend of pulmonary fungal infection (PFI) has rapidly increased. Changes in the risk factors for, distributions of underlying diseases associated with and clinical characteristics of some individual PFIs have been reported in the past decade. However, data regarding PFIs remain uncertain. This study reports the epidemiological characteristics and trends of PFIs over time in recent years. We applied an automated natural language processing (NLP) system to extract clinically relevant information from the electronic health records (EHRs) of PFI patients at the First Affiliated Hospital of Guangzhou Medical University. Then, a trend analysis was performed. From January 1, 2013, to December 31, 2019, 40,504 inpatients and 219,414 outpatients with respiratory diseases were screened, in which 1368 inpatients and 1313 outpatients with PFI were identified. These patients were from throughout the country, but most patients were from southern China. Upward trends in PFIs were observed in both hospitalized patients and outpatients (P<0.05). The stratification by age showed that the incidence of hospitalized patients aged 14-30 years exhibited the most obvious upward trend, increasing from 9.5 per 1000 patients in 2013 to 88.3 per 1000 patients in 2019. Aspergillosis (56.69%) was the most common PFI, but notably, the incidence rates of Talaromyces marneffei, which used to be considered uncommon, exhibited the most rapid increases. In younger PFI patients, the incidence and trend of PFIs have increased. Infection by previously uncommon pathogens has also gradually increased. Increased attention should be paid to young PFI patients and uncommon PFI pathogen infections.

Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery.

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.

Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China.

BACKGROUND: A novel variant of SARS-CoV-2, the Delta variant of concern (VOC, also known as lineage B.1.617.2), is fast becoming the dominant strain globally. We reported the epidemiological, viral, and clinical characteristics of hospitalized patients infected with the Delta VOC during the local outbreak in Guangzhou, China. METHODS: We extracted the epidemiological and clinical information pertaining to the 159 cases infected with the Delta VOC across seven transmission generations between May 21 and June 18, 2021. The whole chain of the Delta VOC transmission was described. Kinetics of viral load and clinical characteristics were compared with a cohort of wild-type infection in 2020 admitted to the Guangzhou Eighth People's Hospital. FINDINGS: There were four transmission generations within the first ten days. The Delta VOC yielded a significantly shorter incubation period (4.0 vs. 6.0 days), higher viral load (20.6 vs. 34.0, cycle threshold of the ORF1a/b gene), and a longer duration of viral shedding in pharyngeal swab samples (14.0 vs. 8.0 days) compared with the wild-type strain. In cases with critical illness, the proportion of patients over the age of 60 was higher in the Delta VOC group than in the wild-type strain (100.0% vs. 69.2%, p = 0.03). The Delta VOC had a higher risk than wild-type infection in deterioration to critical status (hazards ratio 2.98 [95%CI 1.29-6.86]; p = 0.01). INTERPRETATION: Infection with the Delta VOC is characterized by markedly increased transmissibility, viral loads and risk of disease progression compared with the wild-type strain, calling for more intensive prevention and control measures to contain future outbreaks. FUNDING: National Grand Program, National Natural Science Foundation of China, Guangdong Provincial Department of Science and Technology, Guangzhou Laboratory.

Association between occupational health and safety knowledge and behaviours among migrant workers: results from a cross-sectional study in China.

OBJECTIVES: To assess the relationship between occupational health and safety (OH&S)-related behaviours of migrating workers in China and their knowledge regarding OH&S laws and regulations (L&Rs). MATERIALS AND METHODS: We sampled 1282 migrant workers from 12 labour-intensive manufacturers in Guangdong, China, with a response rate of 98.6%. Self-reported questionnaires were completed by the participants. Logistic regression models were used to examine the association between OH&S-related behaviours and knowledge among migrant workers adjusting for their demographic features and the survey sites. RESULTS: Migrant workers' behaviour of seeking occupational disease (OD) diagnosis and treatment was found to be statistically significantly correlated with their knowledge of all three OH&S L&Rs. A higher score of knowledge regarding these OH&S L&Rs is associated with a better chance to seek OD diagnosis and treatment. The ORs of the high-score group (subjects correctly answered more than one question) versus the low-score group (subjects correctly answered less than or equal to one question) are 2.02 (95% CI: 1.33 to 3.07) for Law of Occupational Disease Prevention and Treatment, 2.89 (95% CI: 1.65 to 5.09) for Regulations on Safe Management of Dangerous Chemicals and Regulations on Labor Protection for Using Toxic Substances in Workplace and 2.25 (95% CI: 1.34 to 3.77) for Work-Related Injury Insurance Regulations. However, knowledge about these L&Rs is not statistically significantly associated with OH&S-related protective behaviours such as wearing a mask or gloves at work. CONCLUSIONS: Knowledge of OH&S L&Rs helps migrant workers in China to seek OD diagnosis and treatment.

Intra-abdominal Pressure Has a Good Predictive Power for 28-Day Mortality: A Prospective Observational Study Conducted in Critically Ill Children.

Objective: Elevated intra-abdominal pressure (IAP) is associated with organ dysfunction in critically ill children. Thus far, the predictive value of IAP for mortality remains unknown. Moreover, only few studies determined normal IAP values in pediatric intensive care unit (PICU) children. This study aimed to determine the predictive value of IAP for mortality and calculate normal IAP values in PICU patients. Methods: This prospective observational study was conducted in two PICUs of two tertiary care university teaching hospitals. Patients admitted to the PICU between December 2013 and November 2015 were included. IAP was determined by bladder pressure measurements performed every 8 h until 48 h or until PICU discharge. All patients (except neonatal patients) aged ≤ 14 years who were admitted to the PICUs and had no history of chemical neuromuscular blockade use, neurogenic bladder, or bladder surgery were enrolled. Binary logistic regression was used to analyze the predictive value of IAP for 28-day mortality. Receiver operating characteristic curves were generated to evaluate the prediction effect of IAP. Results: Overall, 229 patients were enrolled. IAP (hazard ratio 1.09, 95% confidence interval [CI] 1.029-1.161, P = 0.004) and lactic acid (hazard ratio 3.04, 95% CI 1.769-5.21, P < 0.001) were independent predictors of 28-day mortality. Additionally, IAP had good predictive power for 28-day mortality, with an area under the curve of 0.74. The optimal cutoff point was 12.13 mmHg (sensitivity 0.58, specificity 0.80). The Youden index was 0.38.Furthermore, 111 (48.47%) patients without high-risk factors or clinical manifestations of IAH were analyzed to determine normal IAP values, which were 7.57 ± 2.85 mmHg (range, 1.98-13.16 mmHg). There were no significant differences in normal IAP values according to different diseases, sex, age, weight, or body mass index (BMI). Conclusions: IAP has good predictive power for 28-day mortality. The optimal IAP cutoff point is 12.13 mmHg. The IAP reference range is 2.0-13.2 mmHg, which was not associated with factors such as sex, age, weight, and BMI in PICU children. We recommend that IAP be included in critical illness scoring systems in the future. IAP >12.13 mmHg may be more suitable for IAH definition in PICU patients.

Effects of intravitreal conbercept before panretinal photocoagulation on lipid exudates in diabetic macular documented by optical coherence tomography.

AIM: To evaluate the effects of intravitreal conbercept (IVC) as adjunctive treatments before panretinal photocoagulation (PRP) to decrease hyperreflective dots (HRDs) in Chinese proliferative diabetic retinopathy (PDR) patients. METHODS: Fifty-nine enrolled patients were categorized into 2 groups: single dose IVC (0.5 mg/0.05 mL) 1wk before PRP (Plus group) or PRP only (PRP group). Six months later, we measured the best corrected visual acuity (BCVA), central macula thickness (CMT) by optical coherence tomography and counted the number of HRDs in different retina layers. RESULTS: The average CMT significantly decreased in Plus group but increased in PRP group. The average BCVA in the Plus group was also significantly better than that in the PRP group. Total HRDs decreased in the Plus group but increased in PRP group significantly. IVC pre-treatment has beneficial effects on reducing HRDs forming in the inner retina layer while the PRP alone increased the HRDs in the outer retina layer. CONCLUSION: IVC is a promising adjunctive treatment to PRP in the treatment of PDR. Single dose IVC one week before PRP is suggested to improve retina blood-retina barrier, decrease lipid exudate and inhibit HRDs development in PDR.