Study on prescription medication mode and mechanism of traditional Chinese medicine in the treatment of noncritical COVID-19 based on data mining

Background: As of 2023, coronavirus disease 2019 (COVID-19) is still spreading globally. Therefore, we aim to integrate non-critical COVID-19 high-frequency and high-targeting Chinese medicines to provide a reference for clinical prescriptions to improve COVID-19-related symptoms. Materials and methods: The information on non-critical COVID-19 high-frequency Chinese medicines in the diagnosis and treatment of COVID-19 was obtained by the TCM inheritance support platform. Using network pharmacology and molecular docking technology, high-targeting Chinese medicines with good docking activity with COVID-19 receptors angiotensin-converting enzyme-II (ACE2), 3CLpro and tyrosine-protein kinase receptor UFO (AXL) were obtained. A new prescription for non-critical COVID-19 was established by integrating high-frequency and high-targeting Chinese medicines. Rats with acute lung injury induced by lipopolysaccharide were used as the experimental model. The histopathological changes in the lungs of rats in each group were observed by hematoxylin-eosin staining. The lung coefficient of rats was measured. The levels of IL-6, TNF-a, and IL-1ß in serum were detected by enzyme-linked immunosorbent assay. The mRNA and protein levels of ACE2 and AXL in lung tissue were detected by real-time quantitative polymerase chain reaction and western blot. Results: Through data mining, it was found that there were 39 high-frequency traditional Chinese medicines for non-critical COVID-19 in the diagnosis and treatment guidelines. According to network pharmacology and molecular docking, 30 highly targeted traditional Chinese drugs for COVID-19 were found. The new prescriptions for non-critical COVID-19 were comprehensively obtained, including Glycyrrhizae Radix, Ephedra Herba, Amygdalus Communis Vas, Gypsum Fibrosum, Descurainiae Semen, Atractylodes Lancea, Scutellariae Radix, Amomum Tsao-Ko Crevostet, Forsythiae Fructus, Pogostemon cablin, Magnolia Officinalis. Compared with the LPS-induced lung injury model group, the medium dose of the new prescription group had significantly alleviated pathological changes in lung tissue, decreased lung coefficient, decreased contents of IL-6, TNF-a and IL-1ß, and increased mRNA and protein expression of ACE2 and AXL (P < 0.05). Conclusion: Based on data mining, network pharmacology and molecular docking technology, the new prescription for non-critical COVID-19 established by this method has an anti-inflammatory effect on rats with acute lung injury induced by lipopolysaccharide and can provide a reference for clinicians to alleviate the symptoms related to non-critical COVID-19. [ FROM AUTHOR] Copyright of Traditional Medicine Research is the property of TMR Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Acute Hepatitis of Unknown Origin in Children: Early Observations from the 2022 Outbreak.

Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide. The main characteristics of the affected children were jaundice and gastrointestinal symptoms. Their serum aminotransaminase levels were above 500 IU/L, with negative tests for hepatitis viruses A-E. By 31 May 2022, the outbreak had affected over 800 children under the age of 16 years in more than 40 countries, resulting in acute liver failure in approximately 10%, including at least 21 deaths and 38 patients requiring liver transplantation. There was still no confirmed cause or causes, although there were several different working hypotheses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus serotype 41, or SARS-CoV-2 superantigen-mediated immune cell activation. Here, we review early observations of the 2022 outbreak which may inform diagnosis, treatment, and prevention in the context of an overlapping COVID-19 pandemic.

Genetic causal relationship between COVID-19 and valvular heart diseaseidentified by a two-sample Mendelian randomization study (preprint)

Background Many COVID-19-infected patients have been observed to develop unexplained valvular heart disease (VHD), and the association between COVID-19 and VHD remains inconclusive. Therefore, we conducted a two-sample Mendelian randomization study to infer causality between COVID-19 and VHD from a genetic perspective using COVID-19 genetic tools.Methods This study used genetic variables and summary statistics from COVID-19 and VHD genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) were selected based on the assumption of instrumental variables (IVs). The inverse-variance weighted (IVW) method was used as the main analysis method to summarize the causal effects between exposure and outcome, while the weighted median and weighted mode methods were used as secondary methods. MR-Egger was used to test for horizontal pleiotropy, and the Q-test was used to test for heterogeneity. Sensitivity analysis was conducted using leave-one-out method. Scatterplots, forest plots, and funnel plots were used to visualize the results of MR analysis.Results In this study, seven COVID-19-related SNPs were selected as IVs, and the IVW [odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.04 − 1.28, P = 0.008], weighted median (OR = 1.21, 95% CI = 1.06 − 1.39, P = 0.006), and weighted mode (OR = 1.27, 95% CI = 1.05 − 1.54, P = 0.047) analysis methods suggested a causal effect of COVID-19 on CHD. MR-Egger indicated no evidence of horizontal pleiotropy (P = 0.589), and the Q-test suggested no heterogeneity (IVW, P = 0.349). Sensitivity analysis indicated robustness of the MR analysis results.Conclusions MR analysis revealed a causal effect of COVID-19 infection on the occurrence of VHD, indicating that patients with COVID-19 had a higher risk of VHD.

Empathy, Fear of Disease and Support for COVID-19 Containment Behaviors: Evidence from 34 Countries on the Moderating Role of Governmental Trust (preprint)

The current study investigated the motives that underlie support for COVID-19 preventive behaviorsin a large, cross-cultural sample of 12,758 individuals from 34 countries. We hypothesized that the associations of empathic prosocial concern and fear of disease, with support towards preventive COVID-19 behaviors would be moderated by the individual-level and country-level trust in the government. Results suggest that the association between fear of disease and support for COVID-19 preventive behaviors was strongest when trust in the government was weak (both at individual and country-level). Conversely, the association with empathic prosocial concern was strongest when trust was high, but this moderation was only found at individual-level scores of governmental trust. We discuss how both fear and empathy motivations to support preventive COVID-19 behaviors may be shaped by socio-cultural context, and outline how the present findings may contribute to a better understanding of collective action during global crises.

The reliability and integrity of overall survival data based on follow-up records only and potential solutions to the challenges

Summary Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants’ family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.

Acceptance and Attitude towards the Traditional Chinese Medicine among Asymptomatic COVID-19 Patients: A cross-sectional study in Shanghai Fangcang hospital (preprint)

Objective The Coronavirus Disease 2019 (COVID-19) has brought severe damage to global health and socioeconomics. In China, traditional Chinese medicine (TCM) is the most important complementary and alternative medicine (CAM) and it has shown a beneficial role in the prevention and treatment of COVID-19. However, it is unknown whether patients are willing to accept TCM treatment. The objective of our study is to investigate the acceptance, attitude, and independent predictors of TCM among asymptomatic COVID-19 patients admitted to Shanghai fangcang hospital during the outbreak of the COVID-19 pandemic in Shanghai in 2022.Methods A cross-sectional study was conducted on asymptomatic COVID-19 patients in the largest fangcang hospital in Shanghai, China, from April 22, 2022, to May 25, 2022. Based on the literature review of previous similar studies, a self-report questionnaire was developed to assess the patients’ attitude and acceptance of TCM, and a multivariate logistic regression analysis was conducted to determine the independent predictors of TCM acceptance.Results A total of 1,121 patients completed the survey, of whom 91.53% were willing to accept CAM treatment whereas 8.65% of participants showed no willingness. Among those who were positive to receive CAM treatment, 70.51% of the participants were willing to be treated with Chinese herbal medicine, 62.79% with Chinese patent medicine, 34.96% with massage therapy, 33.20% with moxibustion treatment, and 29.00% with cupping therapy. There were significant differences in the 10 variables such as monthly income level, SARS-CoV-2 vaccination, and patients' cognition and attitude towards TCM among the patients who were willing or unwilling to accept TCM treatment. Multivariate logistic regression analysis revealed that the patients who have received two doses of COVID-19 vaccine (OR = 2.069, 95%CI: 1.029–4.162, P = 0.041 vs not received), understood the culture of TCM (OR = 2.293, 95%CI: 1.029–4.162, P = 0.014 vs not understood), thought TCM needs a longer time to exert efficacy (OR = 1.607, 95%CI: 0.849–3.034, P = 0.145 vs not thought), thought the treatment of TCM is safe (OR = 2.856, 95%CI: 1.334–6.112, P = 0.007 vs not thought), thought the treatment of TCM is effective (OR = 2.724, 95%CI: 1.249–5.940, P = 0.012 vs not thought), and those who informed their attending physician if using TCM for treatment (OR = 3.455, 95%CI:1.867–6.392, P < 0.001 vs not informed) were more likely to accept TCM treatment. However, patients who thought TCM might delay your treatment (OR = 0.256, 95%CI: 0.142–0.462, P < 0.001 not thought) was an independent predictor for unwillingness to accept TCM treatment.Conclusion This is the first study to investigate the acceptance, attitude, and predictors of intention to receive TCM among asymptomatic COVID-19 patients. The next step of this study will be a long-term follow-up of these patients to observe whether accepting TCM treatment will influence their quality of life.

Acute Hepatitis of Unknown Origin in Children: Early Observations from the 2022 Outbreak

Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide. The main characteristics of the affected children were jaundice and gastrointestinal symptoms. Their serum aminotransaminase levels were above 500 IU/L, with negative tests for hepatitis viruses A–E. By 31 May 2022, the outbreak had affected over 800 children under the age of 16 years in more than 40 countries, resulting in acute liver failure in approximately 10%, including at least 21 deaths and 38 patients requiring liver transplantation. There was still no confirmed cause or causes, although there were several different working hypotheses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus serotype 41, or SARS-CoV-2 superantigen-mediated immune cell activation. Here, we review early observations of the 2022 outbreak which may inform diagnosis, treatment, and prevention in the context of an overlapping COVID-19 pandemic. Graphical

A Nonextensive View on the COVID-19 in the World (preprint)

This paper deals with a general Susceptible-Infectious-Removed (SIR) model for the coronavirus disease 2019 (COVID-19) within a non-extensive view. A time-dependent SIR model was modified when particularly regarding control and mitigation measures in response to the societal impacts of epidemics and pandemics. We validated all the theoretical results by fitting the derived q-distributions with data from the COVID-19 pandemic in the world. It was found that not all the changeable fit parameters are independent, some of which shared common properties, a result corroborated by our model prediction. Our modified SIR model was proved to be effective in fitting the COVID-19 epidemic distributions. The relative non-extensive parameter was strongly connected with the freedom of systems, which thus threw a light upon the prevention and treatment of disease next in the world.

Secreted ORF8 is a pathogenic cause of severe Covid-19 and potentially targetable with select NLRP3 inhibitors (preprint)

Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe Covid-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in patients with newly diagnosed Covid-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14+/CD16+ monocytes to induce an inflammasomal cytokine response. The levels of ORF8 protein in the blood correlate with disease mortality in patients with acute infection, and the disease trajectory in patients with severe Covid-19. Furthermore, in vitro the ORF8-induced inflammasome response can be readily inhibited by the select NLRP3 inhibitor MCC950. Our results identify the pathogenic cause and mechanism of severe disease, and a potential new treatment of severe Covid-19.

Familial Mechanisms Linking COVID-19 Lockdown with Mental Health Problems in Singaporean Children and Adolescents (preprint)

The COVID-19 pandemic and related confinement measures have profound impacts on the mental health of children and adolescents. This study investigated familial mechanisms underlying such impacts by studying the unique case of Singapore, which has undergone a period of local transmission without many restrictions (February–March 2020), followed by a nationwide lockdown (April–May 2020). In June 2020, we collected retrospective reports on everyday activities, social relationships, and mental health of 164 children and adolescents (Mage = 14.3, Range = 7-18, 49% female) across three timepoints: Pre-pandemic, Pre-lockdown, and Lockdown. Parental mental health, parenting values and practices were also collected. Multilevel modelling showed increased mental health problems in children from Pre-pandemic to Pre-lockdown, and from Pre-lockdown to Lockdown. Mediation analyses indicated that the increase in children’s mental health problems from Pre-pandemic to Pre-lockdown was partially explained by a decrease in time spent outdoors, an increase in their conflict with fathers, and an increase in their mothers’ mental health problems, with the last factor being the only significant mediator when all three factors were considered simultaneously. The increase in children’s mental health problems from Pre-lockdown to Lockdown was partially explained by a further increase in their mother’s mental health problems. These findings suggest that lockdown measures issued by authority may lead to further deterioration of children’s mental health beyond the pandemic itself. Multiple personal and familial factors may underlie these deteriorations, among which maternal mental health could be especially influential and should be targeted in family support service and intervention.

Biomimetic Design and Mass Production of Sustainable Multiscale Cellulose Fibers‐Based Hierarchical Filter Materials for Protective Clothing

As a core part of personal protective equipment (PPE), filter materials play a key role in individual protection, especially in the fight against the COVID‐19. Here, a high‐performance multiscale cellulose fibers‐based filter material is introduced for protective clothing, which overcomes the limitation of mutual exclusion of filtration and permeability in cellulose‐based filter materials. With the hierarchical biomimetic structure design and the active surface of multiscale cellulose fibers, high PM2.5 removal efficiency of ≈92% is achieved with the high moisture transmission rate of 8 kg m−2 d−1. Through a simple and effective dip‐coating and roll‐to‐roll process, the hierarchical filter materials can be made on a large scale and further fabricated into high‐quality protective clothing by industrial production equipment. [ABSTRACT FROM AUTHOR] Copyright of Advanced Materials Technologies is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Analysis and evaluation of 670 convalescent plasma samples from patients with COVID-19 infection

Objective: To systematically analyze the 670 convalescent plasma (CP) samples from patients with coronavirus disease 2019 (COVID-19).

Quercetin as a potential treatment for COVID-19-induced acute kidney injury: Based on network pharmacology and molecular docking study.

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.

How did COVID-19 Impact the Lives and Perceived Well-being of Parents? Using the Case of Singapore to Investigate the Mechanisms (preprint)

The COVID-19 pandemic presents a significant challenge to the lives and well-being of families with underaged children. Although previous studies have documented COVID-related deterioration in well-being and identified protective and risk factors, the mechanisms under which the pandemic leads to worsened well-being remain unclear. In addition, from a policymaker’s perspective, it is important to differentiate between the effects of government-issued infection control measures (such as lockdown) and families’ voluntary responses when facing the coronavirus (such as self-quarantine) on well-being. Using Singapore as an example, we collected retrospective self-reports on the everyday activities, stressors, and well-being of parents and other caregivers at three timepoints: before local transmission (Pre-pandemic), after local transmission but before the “circuit breaker” (Pandemic), and during the “circuit breaker” (Lockdown). We estimated the effects of the pandemic itself and families’ voluntary responses to it by contrasting Pandemic against Pre-pandemic, and we estimated the additional effects of imposed lockdown measures by contrasting Lockdown against Pandemic. Results showed significant changes in jobs and income, childcare arrangement, family dynamics, and parents’ emotional well-being throughout the three timepoints. Both mothers and fathers reported to worry most about the health and safety of family members and self. Mothers’ time spent on housework partially mediated the effect of lockdown on their emotional well-being, and parents’ conflict with other adults in the household partially mediated the effects of both pandemic and lockdown on their emotional well-being. The effects of pandemic and lockdown were also moderated by parents’ age, education level, and fathers’ authoritarian values.