Vaccination status for mild and asymptomatic infections with SARS-CoV-2 Omicron BA.2 variant in Shanghai.

This study aimed to evaluate the effects of different vaccine regimens on mild and asymptomatic infections with SARS-CoV-2 Omicron BA.2 variant in Shanghai. All asymptomatic patients and those with mild symptoms of Omicron infections were recruited from three major Fangcang shelter hospitals between March 26, 2022 and May 20, 2022. Nucleic acid for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction methods in nasopharyngeal swabs was assessed every day during the hospitalization. The value of cycle threshold lower than 35 was considered as positive result of SARS-CoV-2. A total of 214 592 cases were included in this study. The proportion of the asymptomatic patients was 76.90% and 23.10% of the recruited patients had mild symptoms. The median (interquartile range [IQR]: 25-75) duration of viral shedding (DVS) was 7 (5-10) days among all participants. The DVS varied greatly among different age groups. Children and the elderly had longer DVS compared with the adults. The booster shot of inactivated vaccine contributed to the shorter DVS in patients aged ≥70 years compared with the unvaccinated patients (8 [6-11] vs. 9 [6-12] days, p = 0.002]. Full inactivated vaccine regimen contributed to the shorter DVS in patients aged 3-6 years (7 [5-9] vs. 8 [5-10] days, p = 0.001]. In conclusion, the full inactivated vaccine regimen on children aged 3-6 years and booster inactivated vaccine regimen on the elderly aged ≥70 years appeared to be effective in reducing DVS. The booster vaccine regimen should be rigorously promoted and implemented.

Prevention of nosocomial COVID-19 infections in otorhinolaryngology-head and neck surgery.

Coronavirus disease 2019 (COVID-19) has rapidly evolved into a pandemic, causing a global public health crisis. Many frontline healthcare workers providing ear, nose and throat services have been reported to contract COVID-19 at work. Early during the COVID-19 outbreak, several medical professionals in Otolaryngology-Head and Neck Surgery were infected in Wuhan, China. A series of measures were then taken immediately, which successfully halted the spread of the disease. Here we would like to share the lessons we have learned, and our experience to protect our health care workers during the COVID-19 pandemic.

Chemical composition characteristics and source analysis of PM2.5 in Jiaxing, China: Insights into the effect of COVID-19 outbreak.

Jiaxing is a medium-sized city in the Yangtze River Delta (YRD), which showed complex local and surrounding pollution sources. To study the COVID-19 impact on the ambient PM2.5 in Jiaxing, we collected the PM2.5 samples from January 2 to April 25, 2020 and analyzed their chemical compositions (including carbon components, water-soluble ions (WSIs), and inorganic elements). The concentration of PM2.5 was 83.13 ± 30.93 µg/m3 before COVID-19 pandemic, and then remarkably decreased with COVID-19 outbreak due to the suspension of mobility and industrial activities. Meanwhile, the concentrations of main chemical species (carbon components, water-soluble ions and inorganic elements) of PM2.5 all decreased from period A (January 2 to 20, 2020) to period B (January 23 to February 10, 2020). Moreover, Trajectory clustering analysis showed that close-range transport was one of the dominant factors throughout all the period, except for period D (April 1 to 25, 2020). In addition, PSCF model indicated that the COVID-19 outbreak resulted in a significant decrease of WPSCF value. This study highlighted the differences in chemical compositions and sources of PM2.5 since COVID-19 pandemic were reported and provide a better understanding of the impact of COVID-19 outbreak on PM2.5.

SARS-CoV-2 proteins monitored by long-range surface plasmon field-enhanced Raman scattering with hybrid bowtie nanoaperture arrays and nanocavities.

The identification of biomacromolecules by using surface-enhanced Raman scattering (SERS) remains a challenge because of the near-field effect of traditional substrates. Long-range surface plasmon resonance (LRSPR) is a special type of surface optical phenomenon that provides higher electromagnetic field enhancement and longer penetration depth than conventional surface plasmon resonance. To break the limit of SERS detection distance and obtain a SERS substrate with increased enhancement ability, a bowtie nanoaperture array was sandwiched between two symmetric dielectric environments. Then, an Au mirror was inserted to form a metal-insulator-metal configuration. Finite-difference time-domain simulations revealed that numerous hybrid modes can be provided by this novel configuration (denoted as long-range SERS [LR-SERS] substrate). In particular, the LRSPR mode can be excited and reach the maximum value through the regulation of the polarizations of the incident light and the geometrical parameters of the LR-SERS substrate. The optimized LR-SERS substrate was then applied to detect SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. This substrate displayed ultralow detection limits of ∼9.2 and ∼11.3 pg mL-1 for the S and N proteins, respectively. Moreover, with the help of principal component analysis and receiver operating characteristic methods, our fabricated sensors exhibited excellent selectivity and hold great potential for the diagnosis of SARS-CoV-2 proteins in real samples.

Study on component-target-pathway multiple interactive network to reveal mechanism of Houttuynia cordata in treatment

Objective: To analyze the molecular biological mechanism of Houttuynia cordata in treatment of viral pneumonia based on network pharmacology, and to evaluate its feasibility in prevention and treatment of Corona Virus Disease 2019 (COVID-19).

Effects of growth hormone/estrogen/androgen on COVID-19-type proinflammatory responses in normal human lung epithelial BEAS-2B cells.

BACKGROUND: COVID-19 is a disease caused by SARS-CoV-2, which can cause mild to serious infections in humans. We aimed to explore the effect of growth hormone (GH)/estrogen/androgen in normal human lung epithelial BEAS-2B cells on COVID-19-type proinflammatory responses. METHODS: A BEAS-2B COVID-19-like proinflammatory cell model was constructed. After that, the cells were treated with GH, 17ß-estradiol (E2), and testosterone (Tes) for 24 h. CCK-8 assays were utilized to evaluate cell viability. The mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 were measured by qRT‒PCR and Western blotting, respectively. ELISAs were performed to determine IL-6, MCP-1, MDA and SOD expression. Flow cytometry was used to measure ROS levels. Finally, MAPK/NF-κB pathway-related factor expression was evaluated. RESULTS: The COVID-19-type proinflammatory model was successfully constructed, and 1000 ng/mL RBD treatment for 24 h was selected as the condition for the model group for subsequent experiments. After RBD treatment, cell viability decreased, the mRNA expression of ACE2, AGTR1, TMRRSS2, and ISG15 and the protein expression of ACE2, AGTR1, TMRRSS2, and ISG15 increased, IL-6, MCP-1, MDA and ROS levels increased, and MDA levels decreased. The mRNA levels of MAPK14 and RELA increased, but the protein levels did not change significantly. In addition, phospho-MAPK14 and phospho-RELA protein levels were also increased. Among the tested molecules, E2 had the most pronounced effect, followed by GH, while Tes showed the opposite effect. CONCLUSION: GH/E2 alleviated inflammation in a COVID-19-type proinflammatory model, but Tes showed the opposite effect.

In Situ Surface-Enhanced Raman Scattering Detection of a SARS-CoV-2 Biomarker Using Flexible and Transparent Polydimethylsiloxane Films with Embedded Au Nanoplates

Coronavirus disease 2019 (COVID-19) remains an ongoing issue worldwide and continues to disrupt daily life. Transmission of infection primarily occurs through secretions when in contact with infected individuals, but more recent evidence has shown that fomites are also a source of virus transmission, especially in cold-chain logistics. Traditional nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contamination in cold-chain logistics is time-consuming and inaccurate because of the multiplex sampling sites. Surface-enhanced Raman spectroscopy (SERS) provides a rapid, sensitive, and label-free detection route for various molecules, including viruses, through the identification of the characteristic peaks of their outer membrane proteins. In this study, we embedded arbitrarily orientated gold nanoplates (Au NPLs) in polydimethylsiloxane (PDMS) elastomer and used it as biosensor for the ultrasensitive detection of the SARS-CoV-2 spike protein in cold-chain logistics. This transparent and flexible substrate can be wrapped onto arbitrary surfaces and permits light penetration into the underlying contact surface, enabling in situ and point-of-care SERS diagnostics. The developed assay displayed high reproducibility (8.7%) and a low detection limit of 6.8 x 10(-9) g mL(-1), indicating its potential to serve as a promising approach with increased accuracy and sensitivity for the detection of the S protein.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

Prognostic Value of Machine Learning in Patients with Acute Myocardial Infarction.

(1) Background: Patients with acute myocardial infarction (AMI) still experience many major adverse cardiovascular events (MACEs), including myocardial infarction, heart failure, kidney failure, coronary events, cerebrovascular events, and death. This retrospective study aims to assess the prognostic value of machine learning (ML) for the prediction of MACEs. (2) Methods: Five-hundred patients diagnosed with AMI and who had undergone successful percutaneous coronary intervention were included in the study. Logistic regression (LR) analysis was used to assess the relevance of MACEs and 24 selected clinical variables. Six ML models were developed with five-fold cross-validation in the training dataset and their ability to predict MACEs was compared to LR with the testing dataset. (3) Results: The MACE rate was calculated as 30.6% after a mean follow-up of 1.42 years. Killip classification (Killip IV vs. I class, odds ratio 4.386, 95% confidence interval 1.943-9.904), drug compliance (irregular vs. regular compliance, 3.06, 1.721-5.438), age (per year, 1.025, 1.006-1.044), and creatinine (1 µmol/L, 1.007, 1.002-1.012) and cholesterol levels (1 mmol/L, 0.708, 0.556-0.903) were independent predictors of MACEs. In the training dataset, the best performing model was the random forest (RDF) model with an area under the curve of (0.749, 0.644-0.853) and accuracy of (0.734, 0.647-0.820). In the testing dataset, the RDF showed the most significant survival difference (log-rank p = 0.017) in distinguishing patients with and without MACEs. (4) Conclusions: The RDF model has been identified as superior to other models for MACE prediction in this study. ML methods can be promising for improving optimal predictor selection and clinical outcomes in patients with AMI.

A rare case of drug-induced bradycardia associated with the just low dose use of methylprednisolone in a child with COVID-19.

Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID-19). However, we present the case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long-term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID-19 when MP is considered in COVID-19.

Analysis of Factors Influencing Stock Market Volatility Based on GARCH-MIDAS Model

This paper further extends the existing GARCH-MIDAS model to deal with the effect of microstructure noise in mixed frequency data. This paper has two highlights. First, according to the estimation of the long-term volatility components of the GARCH-MIDAS model, rAVGRV is adopted to substitute for the RV estimator. rAVGRV uses the rich data sources in tick-by-tick data and significantly corrects the impact of the microstructure noise on volatility estimation. Second, besides introducing macroeconomic variables (i.e., macroeconomic consistency index (MCI), deposits in financial institutions (DFI), industrial value-added (IVA), and M2), Chinese Economic Policy Uncertainty (CEPU) index and Infectious Disease Equity Market Volatility Tracker (EMV) are introduced in the long-run volatility component of the GARCH-MIDAS model. As indicated by the results of this paper, the rAVGRV-based GARCH-MIDAS is slightly better than the RV model-based GARCH-MIDAS. In addition to the common macroeconomic variables significantly impacting stock market volatility, CEPU also substantially impacts stock market volatility. Nevertheless, the effect of EMV on the stock market is insignificant.

Causal Relationships Between Social Isolation and Osteoarthritis: A Mendelian Randomization Study in European Population.

OBJECTIVE: We aimed to investigate the causal relationships between social isolation and osteoarthritis. METHODS: Publicly available genome-wide association study (GWAS) summary statistics of social isolation and osteoarthritis in European population were obtained from the Neale lab Consortium and the Medical Research Council-Integrative Epidemiology Unit (MRC-IEU) consortium, respectively. Single nucleotide polymorphisms (SNPs) associated with the traits were identified by P < 5×10-8 and linkage disequilibrium r2 < 0.1. Three Mendelian randomization (MR) methods including the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were used to assess the potential causal effect of social isolation on osteoarthritis and the potential causal effect of osteoarthritis on social isolation. Leave-one-out analysis and test of directional horizontal pleiotropy via MR-Egger regression were performed as sensitivity analyses. RESULTS: When evaluating the causal effect of social isolation on osteoarthritis, five SNPs (rs12364432, rs13291079, rs2352075, rs4958586, rs599550) significantly associated with social isolation were studied as instruments, and social isolation was found to be causally associated with increased risk of osteoarthritis (odds ratio [OR] 1.197 (95% confidence interval (CI) 1.096-1.308) estimated by the IVW method). When evaluating the causal effect of osteoarthritis on social isolation, six SNPs (rs10405617, rs12133235, rs13107325, rs2290573, rs3771501, rs75621460) significantly associated with osteoarthritis were studied as instruments but no causal effect of osteoarthritis on social isolation was found (OR 1.104 (95% CI 0.887-1.375) estimated by the IVW method). Consistent causal relationships were observed when estimated by the weighted median estimator and MR-Egger regression. Leave-one-out analysis and test of directional horizontal pleiotropy suggested the robustness of the above findings. CONCLUSION: Social isolation is causally associated with osteoarthritis, and further work is needed to investigate the potential mechanisms.

Chinese Society of Anesthesiology expert consensus on anesthetic management of cardiac surgical patients with suspected or confirmed Coronavirus disease 2019

The outbreak of a new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in China in December 2019 has brought serious challenges to disease prevention and public health. Patients with severe coronavirus disease 2019 (COVID-19) who undergo cardiovascular surgery necessitate extremely high demands from anesthesia personnel, and face high risks of mortality and morbidity. Based on the current understanding of COVID-19 and the clinical characteristics of cardiovascular surgical patients, the authors provide anesthesia management guidelines for cardiovascular surgery along with the prevention and control of COVID-19.

Triage Modeling for Differential Diagnosis Between COVID-19 and Human Influenza A Pneumonia: Classification and Regression Tree Analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic has lasted much longer than an influenza season, but the main signs, symptoms, and some imaging findings are similar in COVID-19 and influenza patients. The aim of the current study was to construct an accurate and robust model for initial screening and differential diagnosis of COVID-19 and influenza A. Methods: All patients in the study were diagnosed at Fuyang No. 2 People's Hospital, and they included 151 with COVID-19 and 155 with influenza A. The patients were randomly assigned to training set or a testing set at a 4:1 ratio. Predictor variables were selected based on importance, assessed by random forest algorithms, and analyzed to develop classification and regression tree models. Results: In the optimal model A, the best single predictor of COVID-19 patients was a normal or high level of low-density lipoprotein cholesterol, followed by low level of creatine kinase, then the presence of <3 respiratory symptoms, then a highest temperature on the first day of admission <38°C. In the suboptimal model B, the best single predictor of COVID-19 was a low eosinophil count, then a normal monocyte ratio, then a normal hematocrit value, then a highest temperature on the first day of admission of <37°C, then a complete lack of respiratory symptoms. Conclusions: The two models provide clinicians with a rapid triage tool. The optimal model can be used to developed countries/regions and major hospitals, and the suboptimal model can be used in underdeveloped regions and small hospitals.

Discussion on artemisinin and its derivatives for treatment of COVID-19

Since the initial cases of the Coronavirus Disease in 2019 (COVID-19) occurred in Wuhan in December 2019, more and more cases have been found and confirmed, not only in central China but also in other countries. Given there are still no effective drugs many approved "old drugs" are in clinical test for treating COVID-19 at present. Artemisinin, a first-line antimalarial drug recommended by WHO, has been validated to possess a variety of pharmacological effects, including, without limitation, antiinflammatory, immune regulation, anti-pulmonary fibrosis, antibacterial, antiviral and cardiovascular effects, and the like. In this paper, various pharmacological effects of Artemisinin and its derivatives have been summarized, with the emphasis on the mechanism of action, so as to explore its potential medicinal value, especially for treating COVID-19.

Potential mechanism analysis of respiratory system treated by Tankejing based on network pharmacology

Objective: To study the potential mechanism of Tankejing in the treatment of respiratory system based on network pharmacology, and to evaluate the possibility of Tankejing in the prevention and treatment of COVID-19 pneumonia.

Efficacy of simplified-cognitive behavioral therapy for insomnia(S-CBTI) among female COVID-19 patients with insomnia symptom in Wuhan mobile cabin hospital.

BACKGROUND: The outbreak of Coronavirus Disease-2019 (COVID-19) caused great psychological distress often with comorbid insomnia. Insomnia is common in patients with COVID-19 admitted to mobile cabin hospitals. Insomnia may lead to immune dysfunction, a condition not conducive to recovery from COVID-19. The use of sedative-hypnotic drugs is limited by their inhibitory effect on the respiratory system. A paucity of research is available regarding psychotherapy interventions to improve insomnia symptoms among  patients with COVID-19. In the general population, sleep problems are more common in women than in men; insomnia in women patients requires special attention. The aim of this study was to develop simplified-cognitive behavioral therapy for insomnia (S-CBTI) for patients with COVID-19 and comorbid insomnia symptoms and to verify its effectiveness through a self-control trial. A second aim was to compare the effectiveness of S-CBTI between acute and chronic insomnia among women with COVID-19 and comorbid insomnia symptoms in Wuhan Jianghan Cabin Hospital. METHODS: S-CBTI consisted of education on COVID-19 and sleep hygiene, stimulus control, sleep restriction, and self-suggestion relaxation training over a period of two consecutive weeks. Of 67 women, 66 completed psychological intervention and baseline and post-intervention assessments. There were 31 women with acute insomnia and 35 with chronic insomnia. The Insomnia Severity Index (ISI) score and self-compiled sleep data were assessed at baseline and post-intervention, and subjective sleep evaluations were assessed at days 4, 7, 12, and 14. RESULTS: The ISI score, sleep latency, night sleep time, and sleep efficiency were statistically significantlly improved from baseline to post-intervention by paired T-test. After the intervention, the mean ISI score of the acute insomnia group was lower than that of the chronic insomnia group. The reduction of the ISI score and the improvement of sleep time from baseline to post-intervention in the acute insomnia group were greater than those in the chronic insomnia group. Utilization of sedative-hypnotic drugs in the acute insomnia group was less than that in the chronic insomnia group, and the difference was statistically significant. CONCLUSIONS: S-CBTI can improve the insomnia symptoms of women with COVID-19 in mobile cabin hospitals, especially for stress-related acute insomnia.

Patients With A High-Risk Common Type COVID-19 Pneumonia May Be the Optimal Time for Methylprednisolone Therapy: A Retrospective Cohort Study (preprint)

Background: The optimal timing of corticosteroid treatment for coronavirus disease 2019(COVID-19) pneumonia is uncertain. We evaluated the clinical outcomes of methylprednisolone therapy (MPT) for patients with a high-risk common type(HRCT) COVID-19 pneumonia. Methods: We conducted a multi-centre retrospective cohort study in northeast China. A comparison was performed between the standard treatment (SDT) group and the SDT+MPT group to determine the efficacy of methylprednisolone in treating HRCT COVID-19 pneumonia. Results: We collected the medical records of 403 patients with HRCT COVID-19 pneumonia (127 in the SDT+MPT group and 276 in the SDT group). None of the patients had received mechanical ventilation or died. Further, there had been no side-effects associated with of MPT. Patients in the SDT+MPT group treated with methylprednisolone received an intravenous injection for a median interval of five days (interquartile range of three to seven days). The trends in lymphocyte count, C-reactive protein, interleukin 6, lactic acid dehydrogenase, respiratory rate, SpO2, PaO2, D-dimer and body temperature were similar between the SDT+MPT and SDT groups. The results for the SDT+MPT group seems to be faster improved than the SDT group; however, the results were not statistically significant. Clinical outcomes revealed that the average hospitalisation days and the rate of progression to severe type COVID-19 pneumonia in both the SDT+MPT group and the SDT group were present in 14.56±0.57days vs 16.55±0.3days(p=0.0009) and 21.26%(27/127) vs 32.4%(89/276)(p=0.0254), respectively. The 16-day nucleic acid negative rate was higher in the SDT+MPT group than the SDT group, 81.73% (104/127) vs 65.27% (180/276) (p = 0.0014). Conclusions: MPT effectively prevents patients with HRCT COVID-19 pneumonia from progressing to the severe stage. Therefore, patients with HRCT may be the optimal timing for MPT.Funding Statement: 1.The National Key Laboratory of Sponsored by Open Project of State Key Laboratory of Respiratory Disease (Project Funding Number：SKLRD-OP-201902)” 2.The National Key Laboratory of Urban Water Resources and Water Environment Full Funds. (Project Funding Number：ESK201602.)Declaration of Interests: We have not any conflict of interests to declare.Ethics Approval Statement: Ethical approval by the institutional ethics board of the Qun'li branch of the First Affiliated Hospital of Harbin Medical University and Kang'an Hospital of Mudanjiang was obtained for the analysis and summary of clinical data from COVID-19-infected inpatients.

Disease Burden Attributable to the First Wave of COVID-19 in China and the Effect of Timing on the Cost-Effectiveness of Movement Restriction Policies.

OBJECTIVES: Movement restriction policies (MRPs) are effective in preventing/delaying COVID-19 transmission but are associated with high societal cost. This study aims to estimate the health burden of the first wave of COVID-19 in China and the cost-effectiveness of early versus late implementation of MRPs to inform preparation for future waves. METHODS: The SEIR (susceptible, exposed, infectious, and recovered) modeling framework was adapted to simulate the health and cost outcomes of initiating MRPs at different times: rapid implementation (January 23, the real-world scenario), delayed by 1 week, delayed by 2 weeks, and delayed by 4 weeks. The end point was set as the day when newly confirmed cases reached zero. Two costing perspectives were adopted: healthcare and societal. Input data were obtained from official statistics and published literature. The primary outcomes were disability-adjusted life-years, cost, and net monetary benefit. Costs were reported in both Chinese renminbi (RMB) and US dollars (USD) at 2019 values. RESULTS: The first wave of COVID-19 in China resulted in 38 348 disability adjusted life-years lost (95% CI 19 417-64 130) and 2639 billion RMB losses (95% CI 1347-4688). The rapid implementation strategy dominated all other delayed strategies. This conclusion was robust to all scenarios tested. At a willingness-to-pay threshold of 70 892 RMB (the national annual GDP per capita) per disability-adjusted life-year saved, the probability for the rapid implementation to be the optimal strategy was 96%. CONCLUSIONS: Early implementation of MRPs in response to COVID-19 reduced both the health burden and societal cost and thus should be used for future waves of COVID-19.