Coping with COVID: Performance of China's hierarchical medical system during the COVID-19 pandemic.

Objective: The COVID-19 pandemic has challenged the health system worldwide. This study aimed to assess how China's hierarchical medical system (HMS) coped with COVID-19 in the short-and medium-term. We mainly measured the number and distribution of hospital visits and healthcare expenditure between primary and high-level hospitals during Beijing's 2020-2021 pandemic relative to the 2017-2019 pre-COVID-19 benchmark period. Methods: Hospital operational data were extracted from Municipal Health Statistics Information Platform. The COVID-19 period in Beijing was divided into five phases, corresponding to different characteristics, from January 2020 to October 2021. The main outcome measures in this study include the percentage change in inpatient and outpatient emergency visits, and surgeries, and changing distribution of patients between different hospital levels across Beijing's HMS. In addition, the corresponding health expenditure in each of the 5 phases of COVID-19 was also included. Results: In the outbreak phase of the pandemic, the total visits of Beijing hospitals declined dramatically, where outpatient visits fell 44.6%, inpatients visits fell 47.9%; emergency visits fell 35.6%, and surgery inpatients fell 44.5%. Correspondingly, health expenditures declined 30.5% for outpatients and 43.0% for inpatients. The primary hospitals absorbed a 9.51% higher proportion of outpatients than the pre-COVID-19 level in phase 1. In phase 4, the number of patients, including non-local outpatients reached pre-pandemic 2017-2019 benchmark levels. The proportion of outpatients in primary hospitals was only 1.74% above pre-COVID-19 levels in phases 4 and 5. Health expenditure for both outpatients and inpatients reached the baseline level in phase 3 and increased nearly 10% above pre-COVID-19 levels in phases 4 and 5. Conclusion: The HMS in Beijing coped with the COVID-19 pandemic in a relatively short time, the early stage of the pandemic reflected an enhanced role for primary hospitals in the HMS, but did not permanently change patient preferences for high-level hospitals. Relative to the pre-COVID-19 benchmark, the elevated hospital expenditure in phase 4 and phase 5 pointed to hospital over-treatment or patient excess treatment demand. We suggest improving the service capacity of primary hospitals and changing the preferences of patients through health education in the post-COVID-19 world.

SARS-CoV-2 Spike Protein Influences Expression of ICOSL and ICAM-2 in Prostate Cancer

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus responsible for the COVID-19 pandemic. The viral protein of SARS-CoV-2, spike protein (SP), mediates entry into host cells, contributing to pathogenesis of COVID-19. Prostate cancer is the most common cancer among men in the United States. Inducible T-cell costimulator ligand (ICOSL) and intercellular cell adhesion molecule 2 (ICAM-2) are expressed in cancer cells and their roles in cancer growth remain controversial. It is unknown if SP can affect the expression of ICAM-2 or ICOSL in prostate cancer. This study investigated the effects of SARS-CoV-2 SP on the expression of ICAM-2 and ICOSL and the time-dependent effect of SP on growth and survival of prostate cancer cells. Methods: The effect of SARS-CoV-2 SP on the survival of a widely-used prostate cancer cell line, LNCaP, was assessed using clonogenic cell survival assay and quick cell proliferation assay. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were performed to investigate the expression of ICAM-2 and ICOSL. The survival of an additional prostate cancer cell line, PC-3, was also evaluated by clonogenic survival assay. Results: After 3 days, a significant decrease in the percentage of colonies in LNCaP cells treated with SP was found, which was paralleled by a decrease in optical density (OD) value in LNCaP cells in the presence of SP. A significant decrease in the percentage of colonies treated with SP was also found in PC-3 cells evaluated by clonogenic survival assay. In addition, the mRNA expression of ICAM-2 was lower, whereas the mRNA expression of ICOSL was higher in SP-treated LNCaP cells. This was supported by protein expressions for ICAM-2 and ICOSL evaluated with IHC. Conclusions: In LNCaP cells, SARS-CoV-2 SP downregulates the expression of ICAM-2 but upregulates the expression of ICOSL. SARS-CoV-2 SP inhibits growth of prostate cancer cells in a time-dependent manner. Further studies are needed to fully address the roles of ICAM-2 and ICOSL in the inhibition prostate cancer growth by SARS-CoV-2 SP.

SARS-CoV-2 spike protein inhibits growth of prostate cancer: a potential role of the COVID-19 vaccine killing two birds with one stone.

To investigate the effects of isolated SARS-CoV-2 spike protein on prostate cancer cell survival. The effects of SARS-CoV-2 spike protein on LNCaP prostate cancer cell survival were assessed using clonogenic cell survival assay, quick cell proliferation assay, and caspase-3 activity kits. RT-PCR and immunohistochemistry were performed to investigate underlying molecular mechanisms. SARS-CoV-2 spike protein was found to inhibit prostate cancer cell proliferation as well as promote apoptosis. Further investigation revealed that anti-proliferative effects were associated with downregulation of the pro-proliferative molecule cyclin-dependent kinase 4 (CDK4). The increased rate of apoptosis was associated with the upregulation of pro-apoptotic molecule Fas ligand (FasL). SARS-CoV-2 spike protein inhibits the growth of LNCaP prostate cancer cells in vitro by a two-pronged approach of downregulating the expression of CDK4 and upregulating FasL. The introduction of SARS-CoV-2 spike protein into the body via COVID-19 vaccination may have the potential to inhibit prostate cancer in patients. This potential beneficial association between COVID-19 vaccines and prostate cancer inhibition will require more extensive studies before any conclusions can be drawn about any in vivo effects in a human model.

Impact of COVID-19 on Male Fertility.

COVID-19, the clinical condition caused by the SARS-CoV-2 virus, has been associated with massive cytokine storm and damage to multiple organ systems. Although evidence for the detection of SARS-CoV-2 virus in the testis remains scarce, testicular damage and dysregulation of gonadotropins associated with inflammation has been reported. Additionally, as a result of the rapidly evolving pandemic, frequently updated medical interventions and public policies leading to delays of care can play a role in fertility. This narrative review aims to summarize the current literature on how COVID-19 may influence male fertility.

Exploring the interaction of quercetin-3-O-sophoroside with SARS-CoV-2 main proteins by theoretical studies: A probable prelude to control some variants of coronavirus including Delta.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

Quality Appraisal of the Pharmacoeconomic Research Literature about Antivirals: A Comparison between Chinese Medicine and Non-Chinese Medicine.

INTRODUCTION: Antiviral activity is a main function of many types of traditional Chinese medicine (TCM), and they may contribute more in the process of certain viral epidemics. Therefore, based on the effectiveness and economy of TCM, we aimed to determine the situation of health economic studies about antivirals, especially the difference between TCM and non-TCM. METHODS: A literature search of three databases was conducted with a time range of January 2000-December 2020, and terms related to health economics and TCM were used as key terms. QHES and CHEERS were used as quality assessment tools. RESULTS: 203 papers were included in our research. After evaluation using QHES and CHEERS, antiviral TCM obtained an overall score of 41.37 ± 4.46/99 in QHES, compared with 48.89 ± 7.25/99 (18.18% higher than TCM) of antiviral non-TCM. CONCLUSION: With a statistically significant difference, the overall quality of pharmacoeconomic research about antiviral non-Chinese medicine is better than that about antiviral Chinese medicine, which may have resulted from researchers' capacities or the absence of a more suitable standard for pharmacoeconomic research. It tells that the quality of pharmacoeconomic studies about TCM still warrants improvement.

A review on the interaction of nucleoside analogues with SARS-CoV-2 RNA dependent RNA polymerase.

The outbreaks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in 2019, have highlighted the concerns about the lack of potential vaccines or antivirals approved for inhibition of CoVs infection. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) which is almost preserved across different viral species can be a potential target for development of antiviral drugs, including nucleoside analogues (NA). However, ExoN proofreading activity of CoVs leads to their protection from several NAs. Therefore, potential platforms based on the development of efficient NAs with broad-spectrum efficacy against human CoVs should be explored. This study was then aimed to present an overview on the development of NAs-based drug repurposing for targeting SARS-CoV-2 RdRp by computational analysis. Afterwards, the clinical development of some NAs including Favipiravir, Sofosbuvir, Ribavirin, Tenofovir, and Remdesivir as potential inhibitors of RdRp, were surveyed. Overall, exploring broad-spectrum NAs as promising inhibitors of RdRp may provide useful information about the identification of potential antiviral repurposed drugs against SARS-CoV-2.

Coronaviruses disease 2019 (COVID-19): Causative agent, mental health concerns, and potential management options.

Coronavirus disease-2019 (COVID-19) pandemic started from Wuhan, China has infected more than 6.7 million individuals and killed more than 390,000 individuals globally. Due to the higher transmissibility and infectiousness, asymptomatic infection, and lack of effective treatment options and vaccine, fatalities and morbidities are increasing day by day globally. Despite physical health consequences, COVID-19 pandemic has created stress and anxiety, as result there is an increased risk of mental illnesses both in the infected and normal individuals. To eradicate these risks, it is necessary to determine the COVID-19 zoonotic source of transmission to humans and clinical manifestations in infected individuals. Although, identification or development of the highly effective therapeutic agents is necessary, however, development of protective strategies against the COVID-19 by enhancing immune responses will be an asset in the current scenarios of the COVID-19 pandemic. In this paper, we discuss the transmission, health consequences, and potential management (therapeutic and preventive) options for COVID-19 disease.

Evidence and speculations: vaccines and therapeutic options for COVID-19 pandemic.

A novel coronavirus (2019-nCov) emerged in China, at the end of December 2019 which posed an International Public Health Emergency, and later declared as a global pandemic by the World Health Organization (WHO). The International Committee on Taxonomy of Viruses (ICTV) named it SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), while the disease was named COVID-19 (Coronavirus Disease- 2019). Many questions related to the exact mode of transmission, animal origins, and antiviral therapeutics are not clear yet. Nevertheless, it is required to urgently launch a new protocol to evaluate the side effects of unapproved vaccines and antiviral therapeutics to accelerate the clinical application of new drugs. In this review, we highlight the most salient characteristics and recent findings of COVID-19 disease, molecular virology, interspecies mechanisms, and health consequences related to this disease.

Emergence of a Novel Coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2: Biology and Therapeutic Options.

The new decade of the 21st century (2020) started with the emergence of a novel coronavirus known as SARS-CoV-2 that caused an epidemic of coronavirus disease (COVID-19) in Wuhan, China. It is the third highly pathogenic and transmissible coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in humans. The source of origin, transmission to humans, and mechanisms associated with the pathogenicity of SARS-CoV-2 are not yet clear, however, its resemblance to SARS-CoV and several other bat coronaviruses was recently confirmed through genome sequencing-related studies. The development of therapeutic strategies is necessary in order to prevent further epidemics and cure infections. In this review, we summarize current information about the emergence, origin, diversity, and epidemiology of three pathogenic coronaviruses with a specific focus on the current outbreak in Wuhan, China. Furthermore, we discuss the clinical features and potential therapeutic options that may be effective against SARS-CoV-2.