Robust therapeutic effects on COVID-19 of novel small molecules: Alleviation of SARS-CoV-2 S protein induction of ACE2/TMPRSS2, NOX2/ROS, and MCP-1.

While new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge to prolong the pandemic of COVID-19, robust and safe therapeutics are in urgent need. During the previous and ongoing fight against the pandemic in China, Traditional Chinese Medicine (TCM) has proven to be markedly effective in treating COVID-19. Among active ingredients of TCM recipes, small molecules such as quercetin, glabridin, gallic acid, and chrysoeriol have been predicted to target viral receptor angiotensin-converting enzyme 2 (ACE2) via system pharmacology/molecular docking/visualization analyses. Of note, endothelial dysfunction induced by oxidative stress and inflammation represents a critical mediator of acute respiratory distress syndrome (ARDS) and multi-organ injuries in patients with COVID-19. Hence, in the present study, we examined whether quercetin, glabridin, gallic acide and chrysoeriol regulate viral receptors of ACE2 and transmembrane serine protease 2 (TMPRSS2), redox modulator NADPH oxidase isoform 2 (NOX2), and inflammatory protein of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to mediate therapeutic protection against COVID-19. Indeed, quercetin, glabridin, gallic acide and chrysoeriol completely attenuated SARS-CoV-2 spike protein (S protein)-induced upregulation in ACE2 protein expression in endothelial cells. In addition, these small molecules abolished S protein upregulation of cleaved/active form of TMPRSS2, while native TMPRSS2 was not significantly regulated. Moreover, these small molecules completely abrogated S protein-induced upregulation in NOX2 protein expression, which resulted in alleviated superoxide production, confirming their preventive efficacies against S protein-induced oxidative stress in endothelial cells. In addition, treatment with these small molecules abolished S protein induction of MCP-1 expression. Collectively, our findings for the first time demonstrate that these novel small molecules may be used as novel and robust therapeutic options for the treatment of patients with COVID-19, via effective attenuation of S protein induction of endothelial oxidative stress and inflammation.

The Role of Self-Esteem in the Relationship Between Psychological Capital and Anxiety of Left-Behind Experience College Students During COVID-19 Pandemic: An Online Study

Background There is growing evidence that the COVID-19 pandemic has had a dramatic impact on public mental health. However, less attention has been paid to left-behind experience college students (LBEs). This online study aimed to investigate the relationship between psychological capital (PsyCap) and anxiety among LBEs during COVID-19 pandemic, and further analyze the mediation role of self-esteem between them. Methods A total of 9990 students were chosen using the stratified cluster sampling method. Three self-reported questionnaires were used to assess the PsyCap, self-esteem, and anxiety, respectively. All the statistical analyses were conducted using SPSS 23.0 and R, and to further investigate the mediation effect of self-esteem in the association of PsyCap with anxiety, AMOS 23.0 was used to build a structural equation model. Results PsyCap, self-esteem, and anxiety were significantly correlated among LBEs during the COVID-19 pandemic. PsyCap affects anxiety directly (β = –0.22, SE = 0.051, 95% CI: –0.27, –0.17, P < 0.05). In addition, self-esteem partially mediated the relationship between PsyCap and anxiety (mediating effect value = –0.16, 95% CI: –0.20, –0.13, P < 0.05). Conclusion During the pandemic of COVID-19, left-behind experience had a negative influence on the PsyCap and self-esteem of college students. In addition, for LBEs, self-esteem plays an important mediating role between PsyCap and anxiety. Therefore, from the perspective of PsyCap and self-esteem, schools should translate them into practical educational strategies to enhance the mental health and mitigate the anxiety levels of LBEs.

Efficacy of traditional Chinese exercise for obesity: A systematic review and meta-analysis

Background Obesity is considered one of the biggest public health problems, especially in the background of the coronavirus disease 2019 (COVID-19) lockdown. It is urgent to find interventions to control and improve it. We performed this systematic review and meta-analysis to summarize the effect of traditional Chinese exercise on obesity. Methods We searched PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and WanFang database for updated articles published from the inception of each database to June 2022. Randomized controlled trials (RCTs) on traditional Chinese exercise in weight reduction were included, and related data were extracted. The random-effects model was used to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. Results A total of 701 participants were included in the 10 studies. Compared with the control group, the outcome of body weight [mean difference (MD) = −6.10;95% CI = -8.79, -3.42], body mass index (MD = −2.03;95% CI = -2.66, -1.41), body fat mass (MD = −3.12;95% CI = -4.49, -1.75), waist circumference (MD = −3.46;95% CI = -4.67, -2.24), hip circumference (MD = −2.94;95% CI = -4.75, -1.30), and waist-to-hip ratio (MD = −0.04;95% CI = -0.06, -0.03) in the intervention group had significant differences. Egger's test and funnel plots showed that the potential publication bias of the included studies was slight (p = 0.249). Conclusion Traditional Chinese exercise is an effective treatment for obesity;people under the COVID-19 lockdown could do these exercises to control weight. However, a precise and comprehensive conclusion calls for RCTs on a larger scale with more rigorous designs considering the inferior methodological quality and limited retrieved articles. Systematic review registration www.crd.york.ac.uk/PROSPERO/, identifier CRD42021270015.

COVID-19 and Obesity: Epidemiology, Pathogenesis and Treatment.

The growing prevalence of overweight and obesity has been a worldwide public health issue. During the COVID-19 pandemic, obesity is associated with a higher risk of severity and a worse clinical outcome of SARS-COV-2 infection. This may be because of the chronic low-grade inflammation, impaired immune response and metabolic disorders in obese patients. In this narrative review, we have summarized the association between obesity and COVID-19 and discussed the potential pathogenesis and treatment in these patients. This work may provide practical suggestions on the clinical management of obese COVID-19 patients.

Efficacy of traditional Chinese exercise for obesity: A systematic review and meta-analysis.

Background: Obesity is considered one of the biggest public health problems, especially in the background of the coronavirus disease 2019 (COVID-19) lockdown. It is urgent to find interventions to control and improve it. We performed this systematic review and meta-analysis to summarize the effect of traditional Chinese exercise on obesity. Methods: We searched PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and WanFang database for updated articles published from the inception of each database to June 2022. Randomized controlled trials (RCTs) on traditional Chinese exercise in weight reduction were included, and related data were extracted. The random-effects model was used to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. Results: A total of 701 participants were included in the 10 studies. Compared with the control group, the outcome of body weight [mean difference (MD) = -6.10; 95% CI = -8.79, -3.42], body mass index (MD = -2.03; 95% CI = -2.66, -1.41), body fat mass (MD = -3.12; 95% CI = -4.49, -1.75), waist circumference (MD = -3.46; 95% CI = -4.67, -2.24), hip circumference (MD = -2.94; 95% CI = -4.75, -1.30), and waist-to-hip ratio (MD = -0.04; 95% CI = -0.06, -0.03) in the intervention group had significant differences. Egger's test and funnel plots showed that the potential publication bias of the included studies was slight (p = 0.249). Conclusion: Traditional Chinese exercise is an effective treatment for obesity; people under the COVID-19 lockdown could do these exercises to control weight. However, a precise and comprehensive conclusion calls for RCTs on a larger scale with more rigorous designs considering the inferior methodological quality and limited retrieved articles. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021270015.

Robust therapeutic effects on COVID-19 of novel small molecules: Alleviation of SARS-CoV-2 S protein induction of ACE2/TMPRSS2, NOX2/ROS, and MCP-1

While new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge to prolong the pandemic of COVID-19, robust and safe therapeutics are in urgent need. During the previous and ongoing fight against the pandemic in China, Traditional Chinese Medicine (TCM) has proven to be markedly effective in treating COVID-19. Among active ingredients of TCM recipes, small molecules such as quercetin, glabridin, gallic acid, and chrysoeriol have been predicted to target viral receptor angiotensin-converting enzyme 2 (ACE2) via system pharmacology/molecular docking/visualization analyses. Of note, endothelial dysfunction induced by oxidative stress and inflammation represents a critical mediator of acute respiratory distress syndrome (ARDS) and multi-organ injuries in patients with COVID-19. Hence, in the present study, we examined whether quercetin, glabridin, gallic acide and chrysoeriol regulate viral receptors of ACE2 and transmembrane serine protease 2 (TMPRSS2), redox modulator NADPH oxidase isoform 2 (NOX2), and inflammatory protein of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to mediate therapeutic protection against COVID-19. Indeed, quercetin, glabridin, gallic acide and chrysoeriol completely attenuated SARS-CoV-2 spike protein (S protein)-induced upregulation in ACE2 protein expression in endothelial cells. In addition, these small molecules abolished S protein upregulation of cleaved/active form of TMPRSS2, while native TMPRSS2 was not significantly regulated. Moreover, these small molecules completely abrogated S protein-induced upregulation in NOX2 protein expression, which resulted in alleviated superoxide production, confirming their preventive efficacies against S protein-induced oxidative stress in endothelial cells. In addition, treatment with these small molecules abolished S protein induction of MCP-1 expression. Collectively, our findings for the first time demonstrate that these novel small molecules may be used as novel and robust therapeutic options for the treatment of patients with COVID-19, via effective attenuation of S protein induction of endothelial oxidative stress and inflammation.

THE EFFECT OF BRAND AWARENESS ON CONSUMERS' REPURCHASE INTENTION - A STUDY OF STREAMING MEDIA

[...]few researchers systematically integrate five variables: brand awareness, engagement, customer satisfaction, brand loyalty, and repurchase intention as the framework for the overall study. The brand can raise brand awareness through effective media channels such as advertising, television, and mobile phones, which can help ensure product quality and prestige, reducing the risk of purchasing low-quality products (Sasmita & Suki, 2015;Dab-bous & Barakat, 2020). Researchers identified factors that may influence brand loyalty: brand attachment, brand love, brand connection, brand identity, and brand trust (Park et al., 2010;Atul-kar, 2020) and brand name, brand awareness, product and service quality, and pricing are also affected to brand loyalty (Lau et al., 2006;Foroudi, 2019). Creating stable relationships with customers and encouraging their lifetime loyalty is essential for establishing brand loyalty among customers with their comprehensive understanding and trust of the brand name, brand awareness, product, price, and service quality (Seines, 1998;Malik et al., 2013;Rather & Camilleri, 2019).

Trimer IgG and neutralising antibody response to COVID-19 mRNA vaccination in individuals with sarcoidosis.

Background: Individuals with sarcoidosis are at higher risk for infection owing to underlying disease pathogenesis and need for immunosuppressive treatment. Current knowledge as to how subjects with sarcoidosis respond to different forms of vaccination is limited. We examined quantitative and functional antibody response to COVID-19 vaccination in infection-naive subjects with and without sarcoidosis. Methods: Our prospective cohort study recruited 14 subjects with biopsy-proven sarcoidosis and 27 age-sex matched controls who underwent a two-shot series of the BNT162b2 mRNA vaccine at the University of Illinois at Chicago. Baseline, 4-week and 6-month trimer spike protein IgG and neutralising antibody (nAb) titres were assessed. Correlation and multivariate regression analysis was conducted. Results: Sarcoidosis subjects had a significant increase in short-term antibody production to a level comparable to controls; however, IgG titres significantly declined back to baseline levels by 6 months. Corresponding neutralising assays revealed robust nAb titres in sarcoidosis subjects that persisted at 6 months. A significant and strong correlation between IgG and nAb titres across all time points was observed in the control group. However within the sarcoidosis group, a significant but weak correlation between antibody levels was found. Overall, IgG levels were poor predictors of nAb titres at short- or long-term time points. Conclusions: Sarcoidosis subjects exhibit nAb induced by the BNT162b2 mRNA SARS-CoV-2 vaccine at levels comparable to controls that persists at 6 months indicating conferred immunity. Trimer IgG levels are poor predictors of nAb in subjects with sarcoidosis. Studies of further antibody immunoglobulins and subtypes warrant investigation.

What Do Antibody Studies Tell Us about Viral Infections?

Humoral immunity is an important body defense system against virus infection and is correlated to patient health status [...].

J-shaped associations and joint effects of fasting glucose with inflammation and cytokines on COVID-19 mortality.

OBJECTIVES: The aim of this study was to investigate the dose-response relationship of admission fasting glucose (FBG) with corona virus disease 2019 (COVID-19) mortality and to further evaluate potential interactions of hyperglycemia with inflammation and hypercoagulation on COVID-19 outcomes. METHODS: This retrospective study included 2555 consecutively hospitalized patients with COVID-19, until death or discharge, in Wuhan Union hospital between January 1 and April 9, 2020. The poor early outcomes included admission to intensive care unit, intubation, and deaths occurring within 28 days. We used splines nested in Cox regression to visualize dose-response associations and generalized additive models to fit three-dimensional (3D) trend plots for joint effects of FBG with markers of inflammation and coagulation. RESULTS: J-shaped associations existed between hospitalized mortality or poor early outcomes and FBG with a nadir at 5 mmol/L, which were more evident in women. 3D plots demonstrated significant joint effect trends, and patients with hyperglycemia and high neutrophil-lymphocyte ratio, C-reactive protein, lactate dehydrogenase, procalcitonin, d-dimer, and interleukin-6 had 7.4-25.3-fold risks; the proportions of joint associations attributed to additive interactions reached 30% to 54%. CONCLUSIONS: FBG was associated with hospitalized mortality and poor early outcomes in a J-shaped manner, and a combination of hyperglycemia, inflammation, hypercoagulation, and cytokines conferred a dramatically higher risk.

The Chinese plug-in electric vehicles industry in post-COVID-19 era towards 2035: Where is the path to revival?

The sudden Coronavirus Disease reported at the end of 2019 (COVID-19) has brought huge pressure to Chinese Plug-in Electric Vehicles (PEVs) industry which is bearing heavy burden under the decreasing fiscal subsidy. If the epidemic continues to rage as the worst case, analysis based on System Dynamics Model (SDM) indicates that the whole PEVs industry in China may shrink by half compared with its originally expected level in 2035. To emerge from the recession, feasible industrial policies include (1) accelerating the construction of charging infrastructures, (2) mitigating the downtrend of financial assistance and (3) providing more traffic privilege for drivers. Extending the deadline of fiscal subsidy by only 2 years, which has been adopted by the Chinese central government, is demonstrated to achieve remarkable effect for the revival of PEVs market. By contrast, the time when providing best charging service or most traffic privilege to get the PEVs industry back to normal needs to be advanced by 10 years or earlier. For industrial policy makers, actively implementing the other two promoting measures on the basis of existing monetary support may be a more efficient strategy for Chinese PEVs market to revive from the shadow in post-COVID-19 era.

Comparison of Predictors of COVID-19 Vaccination Intention Between Healthcare Workers and Non-Healthcare Workers in China.

BACKGROUND: Vaccination is an effective strategy to mitigate the spread of COVID-19. This study aimed to compare predictors of vaccination intention between healthcare workers (HCWs) and non-healthcare workers (non-HCWs) in China. METHODS: A web-based cross-sectional survey was conducted among HCWs and non-HCWs. Several bivariate analysis techniques, eg, crosstab with Chi-square, independent t-test and single factor ANOVA, were performed to analyze the correlation. After that, a series of multivariate binary regressions were employed to determine predictors of vaccination intention. RESULTS: Intention was closely and significantly related with gender, perceived vaccination knowledge, perceived importance and effectiveness of vaccine to prevent COVID-19. HCWs and non-HCWs were heterogeneous, since vaccination intention, perceived knowledge, and attitudes (eg, importance, severity, risk) toward COVID-19 or vaccine had statistically significant difference between the two groups. With comparison of predictors of vaccination intention, for HCWs, demographic factors were the major predictors of COVID-19 vaccination intention. Female HCWs and HCWs with a Master's or higher degree were more hesitant about vaccination (P = 0.01 and P < 0.001, respectively), while HCWs had greater vaccination intention as their age increased (P = 0.02). For non-HCWs, perceived vaccination knowledge was the major predictor of COVID-19 vaccination intention (P < 0.001). Additionally, perceived importance and effectiveness of vaccine were predictors for both HCWs and non-HCWs. CONCLUSION: Vaccination intention of HCWs was greater than that of non-HCWs in China. Measures should be taken to improve the vaccination rate based on the predictors of vaccination intention identified in this study. For HCWs, especially those with a high level of education or who were females, the safety and effectiveness of vaccines in use may reinforce their vaccination intention. For non-HCWs, popularization of general medical knowledge, including of vaccine-preventable diseases, may increase their vaccination intention.

Twin peaks of in-hospital mortality among patients with STEMI across five phases of COVID-19 outbreak in China: a nation-wide study.

Lockdown and re-opening may become cyclical due to the recurrent waves of the COVID-19 epidemic. Few studies have examined temporal trends and determinants of in-hospital mortality among patients with ST-segment elevation myocardial infarction (STEMI), a life-threatening condition that requires emergency medical care. Using nation-wide data before, during and after the Wuhan lockdown, we aimed to depict temporal patterns and major determinants of STEMI in-hospital mortality in China across five time periods of the COVID-19 epidemic. We analyzed the data of 283,661 STEMI patients who were admitted to 4,487 chest-pain-centers across China, from January 1, 2019 to May 31, 2020. Compared with the period before the lockdown, STEMI in-hospital mortality increased by 25% (OR 1.25, 95%CI 1.16-1.34) during Early Lockdown, by 12% (OR 1.12, 95%CI 1.03-1.22) during Later Lockdown, by 35% (OR 1.35, 95%CI 1.21-1.50) during Early Lift, and returned to pre-COVID risk (OR 1.04, 95%CI 0.95-1.14) during Later Lift. For each time-period, we observed a clear mortality gradient by timing and types of revascularization procedure. In conclusion, the COVID-19 epidemic had a significant adverse impact on STEMI in-hospital mortality, with bimodal peaks during early lockdown and early lift periods and clear mortality gradients by timing and types of revascularization procedure, independent of the time periods.

A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and memory T cell response in the lungs and protects hamsters against SARS-CoV-2.

Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust memory T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines.

Huge gastric plexiform fibromyxoma presenting as pyemia by rupture of tumor: A case report.

BACKGROUND: Plexiform fibromyxoma (PF) is a rare mesenchymal tumor, with limited case reports worldwide. Common clinical symptoms are abdominal discomfort and bleeding signs, which frequently present slow-onset in reported cases. Herein, we report a case of gastric PF presenting as acute onset and with pyemia accom-panying tumor rupture. We resected the tumor as well as the distal gastric, bulbus duodeni and gallbladder for treatment in emergency surgery. Notably, before the onset of the disease, the patient received coronavirus disease 2019 (COVID-19) vaccines. CASE SUMMARY: A 26-year-old man was admitted to our hospital, due to abdominal pain and fever after having received COVID-19 vaccines. Laboratory examination indicated severe sepsis. Computed tomography scan revealed a large mass in the abdomen. Deformation of the gastrointestinal tract was seen during gastroscopy. After failure of anti-infective treatment and symptoms of shock developed, he received an emergency surgery. We found a huge and partly ruptured mass, with thick purulence. Microscopically, the mass was composed of spindle cells with clarified cytoplasm, accompanied by myxoid stroma and arborizing blood vessels. Immunohistochemistry showed the tumor cells as positive for smooth muscle actin and succinate dehydrogenase subunit B but negative for DOG-1 and CD117. Finally, the patient was diagnosed with gastric PF and discharged from the hospital. CONCLUSION: Gastric PF manifesting as tumor rupture combined with pyemia is rare. Timely surgery is critical for optimal prognosis.

Hybrid Model of Machine Learning Refractory Data Prediction Based on IoT Smart Cities

With the advent of the digital age in recent years, the application of artificial intelligence in urban Internet of Things (IoT) systems has become increasingly important. The concept of smart cities has gradually formed, and smart firefighting under the smart city system has also become important. The method of machine learning is now applied in various fields, but seldom to the data prediction of smart firefighting. Various types of applications including data applications of machine learning algorithms in smart firefighting have yet to be explored. In this article, we propose using machine learning algorithms to predict building fire-resistance data, aiming to provide more theoretical and technical support for IoT smart cities. This article adopts the fire-resistance data of building beam components in a real fire environment, using three integrated machine learning algorithms, Extreme random Tree (ET), AdaBoost, and Gradient Boosting Machine (GBM), and the grey wolf optimization algorithm to optimize. We improve the grey wolf algorithm and combine the grey wolf algorithm with the machine learning model. The algorithm constitutes three machine learning hybrid models: GWO-ET, GWO-AdaBoost, and GWO-GBM. Compared with traditional grid tuning, particle swarm optimization (PSO), and genetic algorithm (GA) optimization, the robustness and accuracy of the three optimization algorithms and the machine learning hybrid algorithm on the data set are compared and analyzed. Performance is measured through various performance comparisons and experimental result comparisons. For various building beam component data sets under real fires, the optimization and comparison show that the mean square error (MSE) of the proposed algorithm is extremely small. The results indicate that the GWO machine learning hybrid model is superior to other models and has a smaller prediction error.

A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases.

Damage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID-19 targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-cytotoxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID-19 complications, and other related diseases. IMPORTANCE With the Delta variant currently fueling a resurgence of new infections in the fully vaccinated population, developing an effective therapeutic drug is especially critical and urgent in fighting COVID-19. In contrast to the many efforts to repurpose existing drugs or address only one aspect of COVID-19, we are developing a novel agent with first-in-class mechanisms of action that address both the viral infection and the overactive immune system in the pathogenesis of the disease. Unlike virus-directed therapeutics that may lose efficacy due to viral mutations, and immunosuppressants that require ideal timing to be effective, this agent, with its unique host-directed antiviral and anti-inflammatory actions, can work against all variants of the virus, be effective during all stages of the disease, and even resolve post-disease damage and complications. Further development of the compound will provide an important tool in the fight against COVID-19 and its complications, as well as future outbreaks of new viruses.