Treatment Of Coronavirus Disease 2019 Research Articles

Clinical profiles and mortality predictors of hospitalized patients with COVID-19 in Ethiopia

BackgroundStudying the characteristics of hospitalized Coronavirus Disease 2019 (COVID-19) patients is vital for understanding the disease and preparing for future outbreaks. The aim of this study was to analyze and describe the clinical profiles and factors associated with mortality among COVID-19 patients admitted to Jimma Medical Center COVID-19 Treatment Center (JMC CTC) in Ethiopia.MethodsAll confirmed COVID-19 patients admitted to JMC CTC between 17 April 2020 and 05 March 2022 were included in this study. Socio-demographic data, clinical information, and outcome variables were collected retrospectively from medical records and COVID-19 database at the hospital. Bivariable and multivariable analyses were performed to determine factors associated with COVID-19 severity and mortality. A P-value < 0.05 was considered statistically significant.ResultsA total of 542 confirmed COVID-19 patients were admitted to JMC CTC, of which 322 (59.4%) were male. Their median age was 48 years (IQR 32–64). About 51% (n = 277) of them had severe COVID-19 upon admission. Patients with hypertension [AOR: 2.8 (95% CI: 1.02–7.7, p = 0.046)], diabetes [AOR: 8.8 (95% CI: 1.2–17.3, p = 0.039)], and underlying respiratory diseases [AOR: 18.8 (95% CI: 2.06–71.51, p = 0.009)] were more likely to present with severe COVID-19 cases. Overall, 129 (23.8%) died in the hospital. Death rate was higher among patients admitted with severe disease [AHR = 5.5 (3.07–9.9) p < 0.001)] and those with comorbidities such as hypertension [AHR = 3.5 (2.28–5.41), p < 0.001], underlying respiratory disease [AHR = 3.4 (1.97–5.94), p < 0.001], cardiovascular disease (CVDs) [AHR = 2.8 (1.73–4.55), p < 0.001], and kidney diseases [AHR = 3.7 (2.3–5.96), p < 0.001].ConclusionAbout half of COVID-19 cases admitted to the hospital had severe disease upon admission. Comorbidities such as hypertension, diabetes, and respiratory diseases were linked to severe illness. COVID-19 admissions were associated with high inpatient mortality, particularly among those with severe disease and comorbidities.

Visual analysis on ferroptosis and its cross-talk to coronavirus disease 2019 (COVID-19)

BackgroundFerroptosis is a new type of programmed cell death. Although ferroptosis has been studied in various aspects, there has been no visual analysis of ferroptosis in coronavirus disease 2019 (COVID-19) to date. It is still a global health concern of the COVID-19 pandemic worldwide, three years after its outbreak. Yet the emergence of the mutant strain Omicron has caused a fourth wave of infections in many countries. The pathogenesis of COVID-19 is still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. MethodsFor this study, CiteSpace 6.2 R4 software was used for bibliometric and visual atlas analysis of ferroptosis-related research, and the Genecards database was used to mine ferroptosis and COVID-19-related genes. ResultsWe found increasing studies about ferroptosis. China and the United States have demonstrated robust scientific innovation over recent years, with extensive collaboration between their institutions and authors. Ferroptosis and COVID-19 were seen to have 13 shared genes, which may be new targets for the treatment of COVID-19 in the future. Most of the shared genes are enriched in tumor necrosis factor (TNF) pathways. The majority of those genes are up-regulated under the cellular response to oxidative stress. Genes including Tumour necrosis factor (TNF), RELA proto-oncogene (RELA), Activating transcription factor 4 (ATF4), Cytochrome b-245 beta chain (CYBB), Jun proto-oncogene (JUN), Mitogen-activated protein kinase 1 (MAPK1) and Heme oxygenase 1 (HMOX1), maybe a breakthrough for ferroptosis and COVID‐19. Whilst previous research has shown there to be a relationship between ferroptosis and COVID‐19, the specific role of ferroptosis remained unclear. Our study aimed to analyze the research status of ferroptosis and its relationship with COVID-19, to provide a useful reference for further prevention and treatment of COVID-19. Overall, uncovering the role of ferroptosis in SARS-CoV-2 infection is important for the development of new treatment strategies for COVID-19.

Paxlovid for the treatment of COVID-19: a systematic review and meta-analysis.

Paxlovid (nirmatrelvir/ritonavir) is a new oral antiviral drug that is used for coronavirus disease 2019 (COVID-19) and is administered to patients with mild to moderate disease for five consecutive days. This meta-analysis aimed to evaluate the efficacy of Paxlovid in COVID-19 patients. PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant publications up to 9 March 2023. Three randomized controlled trial (RCT) studies, one prospective cohort study, and 25 retrospective cohort studies were identified for the meta-analysis. There was a significant difference between the Paxlovid and control groups in terms of hospitalization (RR = 0.53; 95% CI: 0.24-0.69, p < 0.001), all-cause mortality (RR = 0.36; 95% CI: 0.27-0.50, p < 0.001), hospitalization or death (RR = 0.50; 95% CI: 0.37-0.67, p < 0.001), intensive care unit admission (RR = 0.45; 95% CI: 0.27-0.73, p = 0.001), and emergency department visits (RR = 0.67; 95% CI: 0.54-0.83, p < 0.001). However, no significant difference was found between the two groups in terms of COVID-19 rebound (OR = 1.18; 95% CI: 0.82-1.68, p = 0.37). In addition, the Paxlovid group had a significantly shorter hospital length of stay (weighted mean difference WMD = -1.11; 95% CI, -1.81, -0.41; I2 > 50%, p < 0.05), and polymerase chain reaction negative conversion time (WMD = -2.75; 95% CI, -3.60, -1.89, I2 > 50%, p < 0.05) than that of the control group. Paxlovid can be considered an effective therapeutic agent for treating patients with COVID-19.

Potential of 6′‑hydroxy justicidin B from Justicia procumbens as a therapeutic agent against coronavirus disease 2019

BackgroundSince the onset of the coronavirus disease 2019 (COVID-19) pandemic, remarkable advances have been made in vaccine development to reduce mortality. However, therapeutic interventions for COVID-19 are comparatively limited despite these intensive efforts. Furthermore, the rapid mutation capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a characteristic of its RNA structure, has led to the emergence of multiple variants, necessitating a shift from a predominantly vaccine-centric approach to one that encompasses therapeutic strategies. 6′-Hydroxy justicidin B (6′-HJB), an arylnaphthalene lignan isolated from Justicia procumbens, a traditional Chinese medicine, is known for its antiviral properties. Hypothesis/PurposeThe aim of the present study was to assess the effectiveness and safety of 6′-HJB against SARS-CoV-2 in order to determine its potential as a therapeutic agent against COVID-19. MethodsThe efficacy of 6′-HJB was evaluated both in vitro using Vero and Calu-3 cell lines and in vivo using ferrets. The safety assessment included toxicokinetics, safety pharmacology, and Good Laboratory Practice (GLP)-compliant toxicity evaluations following single- and repeated-dose toxicity studies in dogs. ResultsThe anti-SARS-CoV-2 efficacy of 6′-HJB was evaluated through dose-response curve (DRC) analysis using immunofluorescence; 6′-HJB demonstrated superior inhibition of SARS-CoV-2 growth and lower cytotoxicity than remdesivir. In SARS-CoV-2-infected ferret, 6′-HJB showed efficacy comparable to that of the positive control, Truvada. Further GLP toxicity studies corroborated the safety profile of 6′-HJB. Single-dose and 4-week repeated oral toxicity studies in Beagle dogs demonstrated minimal harmful effects at the highest dosages. The lethal dose of 6′-HJB exceeded 2,000 mg kg-1 in Beagle dogs. Toxicokinetic and GLP safety pharmacology studies demonstrated no adverse effects of 6′-HJB on metabolic processes, respiratory or central nervous systems, or cardiac functions. ConclusionThis research highlights both the antiviral efficacy and safety profile of 6′-HJB, underscoring its potential as a novel COVID-19 treatment option. The potential of 6′-HJB was demonstrated using modern scientific methodologies and standards.

The PARP inhibitor rucaparib blocks SARS-CoV-2 virus binding to cells and the immune reaction in models of COVID-19.

To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host; we have, here, assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. The effects of PARP inhibitors on virus uptake were assessed in cell-based experiments using multiple variants of SARS-CoV-2. The binding of rucaparib to spike protein was tested by molecular modelling and microcalorimetry. The anti-inflammatory properties of rucaparib were demonstrated in cell-based models upon challenging with recombinant spike protein or SARS-CoV-2 RNA vaccine. We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients, both of which negatively correlated with lymphocytopaenia. Interestingly, rucaparib, unlike other tested PARP inhibitors, reduced the SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein and viral RNA-induced overexpression of cytokines was down-regulated by the inhibition of PARP1 by rucaparib at pharmacologically relevant concentrations. These results point towards repurposing rucaparib for treating inflammatory responses in COVID-19.

Characterization of the 2ODD genes of DOXC subfamily and its members involved in flavonoids biosynthesis in Scutellaria baicalensis

Background2-oxoglutarate-dependent dioxygenase (2ODD) superfamily is the second largest enzyme family in the plant genome and plays diverse roles in secondary metabolic pathways. The medicinal plant Scutellaria baicalensis Georgi contains various flavonoids, which have the potential to treat coronavirus disease 2019 (COVID-19), such as baicalein and myricetin. Flavone synthase I (FNSI) and flavanone 3-hydroxylase (F3H) from the 2ODDs of DOXC subfamily have been reported to participate in flavonoids biosynthesis. It is certainly interesting to study the 2ODD members involved in the biosynthesis of flavonoids in S. baicalensis.ResultsWe provided a genome-wide analysis of the 2ODDs of DOXC subfamily in S. baicalensis, a total of 88 2ODD genes were identified, 82 of which were grouped into 25 distinct clades based on phylogenetic analysis of At2ODDs. We then performed a functional analysis of Sb2ODDs involved in the biosynthesis of flavones and dihydroflavonols. Sb2ODD1 and Sb2ODD2 from DOXC38 clade exhibit the activity of FNSI (Flavone synthase I), which exclusively converts pinocembrin to chrysin. Sb2ODD1 has significantly higher transcription levels in the root. While Sb2ODD7 from DOXC28 clade exhibits high expression in flowers, it encodes a F3H (flavanone 3-hydroxylase). This enzyme is responsible for catalyzing the conversion of both naringenin and pinocembrin into dihydrokaempferol and pinobanksin, kinetic analysis showed that Sb2ODD7 exhibited high catalytic efficiency towards naringenin.ConclusionsOur experiment suggests that Sb2ODD1 may serve as a supplementary factor to SbFNSII-2 and play a role in flavone biosynthesis specifically in the roots of S. baicalensis. Sb2ODD7 is mainly responsible for dihydrokaempferol biosynthesis in flowers, which can be further directed into the metabolic pathways of flavonols and anthocyanins.

Causal Inference of the Effect of Vaccination on COVID-19 Disease Severity and Need for Intensive Care Unit Admission Among Hospitalized Patients in an African Setting.

Background Coronavirus disease 2019 (COVID-19) is a novel, primarily respiratory, coronavirus that became a pandemic when it spread to over 210 countries and led to the death of over six million people. There is no definitive treatment for COVID-19, but vaccines have been developed that can help prevent severe illness and death. Studies have investigated the effect of vaccination on disease severity and outcome, and the findings indicate that vaccination is linked to a significant reduction in the risk of hospitalization, intensive care unit (ICU) admission, and disease mortality. However, there is a scarcity of evidence in Africa in general, and no similar study has been conducted in Ethiopia yet. Therefore, the study aimed to assess the effect of vaccination on COVID-19 disease severity and the need for ICU admission among hospitalized patients at a private specialty clinic in Ethiopia. Methods A retrospective cohort study was conducted among 126 patients with COVID-19, 41 vaccinated and 85 unvaccinated, who were hospitalized between September 2021 and May 2022. Data were summarized using frequency (percentage) and median (interquartile range (IQR)). To compare the characteristics of the two groups, Chi-square/Fisher's exact and Mann-Whitney U tests at p-values of ≤ 0.05 were used. To identify the effect of vaccination on COVID-19 disease severity, a marginal structural model (MSM) with an inverse probability weighting (IPW) approach using a robust Poisson regression model was fitted. Adjusted relative risk (ARR) and 95% confidence interval (CI) for ARR were used for interpreting the result. Results The cohort included groups that were comparable in terms of their sociodemographic and clinical characteristics. More than half of the participants were older than 60 years (n = 66, 52.4%), were males (n = 71, 56.3%), and had one or more comorbid illnesses (n = 66, 52.4%). At admission, 85 (67.5%) had severe disease, and 11 (8.7%) progressed after hospitalization and required ICU admission, of which three unvaccinated cases died. From the final model, vaccination was found to be associated with a 62% decreased risk of developing severe COVID-19 disease if infected, compared to not getting vaccinated (ARR = 0.38, 95% CI = 0.23-0.65, p < 0.0001). Conclusions The study's findings support previous reports that vaccinated people are less likely to develop severe COVID-19 disease if later infected with the virus, emphasizing the importance of continuing efforts to promote COVID-19 vaccination not only to safeguard individuals but also to confer community-level immunity.

Exploration of medicinal plants as potential therapeutics against COVID-19: molecular insights and drug development prospects with other significant medicinal information a retrospective exposition.

The study aims to explore the potential of medicinal plants and their phytoconstituents as effective inhibitors of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. The focus is on investigating specific medicinal plants known for their pharmacological properties, such as: antioxidant, anti-inflammatory, and immunomodulatory effects, to determine their viability in developing COVID-19 treatments. This study involves a comprehensive study of medicinal plants, including: Withania somnifera (Ashwagandha) and Ocimum sanctum (Holy Basil), known for their beneficial health effects. Molecular docking studies were conducted to assess the interactions between phytoconstituents from these plants and SARS-CoV-2 proteins. The compounds' drug-like characteristics and safety profiles were also evaluated to determine their potential as therapeutic agents. The molecular docking studies revealed that the phytoconstituents from the studied medicinal plants exhibit favourable interactions with SARS-CoV-2 proteins, suggesting their potential as therapeutic targets. These compounds demonstrated promising drug-like characteristics and safety profiles, indicating their suitability for further development as COVID-19-fighting medications. The results indicate that medicinal plants and their bioactive substances hold significant potential for developing therapies against COVID-19. The ability of these organic substances to interact with key viral proteins and provide various therapeutic benefits highlights their potential as multi-functional treatment options. However, further research is necessary to confirm these findings and to understand the full scope of their therapeutic efficacy and safety in clinical settings. Medicinal plants and their phyto-constituents represent a promising avenue for developing effective treatments for COVID-19. The favourable interactions with SARS-CoV-2 proteins and the promising drug-like characteristics observed in this study suggest that these natural compounds could be integral in the fight against the COVID-19 pandemic. Further research and clinical trials are essential to fully validating their potential and translating these findings into practical medical applications.

An in-depth analysis of COVID-19 treatment: Present situation and prospects.

Coronavirus disease 2019 (COVID-19) the most contagious infection caused by the unique type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced a global pandemic that wreaked havoc on the health-care system, resulting in high morbidity and mortality. Several methods were implemented to tackle the virus, including the repurposing of existing medications and the development of vaccinations. The purpose of this article is to provide a complete summary of the current state and future possibilities for COVID-19 therapies. We describe the many treatment classes, such as antivirals, immunomodulators, and monoclonal antibodies, that have been repurposed or developed to treat COVID-19. We also looked at the clinical evidence for these treatments, including findings from observational studies and randomized-controlled clinical trials, and highlighted the problems and limitations of the available evidence. Furthermore, we reviewed existing clinical trials and prospective COVID-19 therapeutic options, such as novel medication candidates and combination therapies. Finally, we discussed the long-term consequences of COVID-19 and the importance of ongoing research into the development of viable treatments. This review will help physicians, researchers, and policymakers to understand the prevention and mitigation of COVID-19.

A real-world study of the differences in Traditional Chinese Medicine diagnosis and treatment rules for coronavirus disease 2019 between Northern and Southern China.

To explore the differences in Traditional Chinese Medicine (TCM) diagnosis and treatment rules for coronavirus disease 2019 (COVID-19) between Northern and Southern China based on the real-world data from 982 COVID-19 patients. All consecutive cases of COVID-19 admitted to the TCM department of designated COVID-19 hospitals in eight provinces and cities were retrospectively analyzed. Patients were divided into a Northern and a Southern group according to the location of the admitting hospital. The symptoms, syndrome elements, syndrome distribution and herbal treatments were analyzed. The core prescriptions were extracted using the multiscale backbone-based network comparison algorithm (msbNC). The distribution of syndrome elements showed that dampness was common in Northern and Southern China, wind and heat were more often present in the South, while fire toxin and spleen deficiency were more often encountered in the North. The distribution of syndromes showed that the South was dominated by heat dampness accumulating in the lung (55.69%), while the North was dominated by dampness-toxin stagnating in the lung (44.90%).The results of core prescription mining showed that dispelling dampness, dispersing wind, clearing heat and strengthening spleen were the common treatment methods in Northern and Southern China. For mild cases, Jinyinhua (Flos Lonicerae) and Lianqiao (Fructus Forsythiae Suspensae) were often used in the South to clear heat and relieve exterior symptoms, while Chaihu (Radix Bupleuri Chinensis) and Huangqin (Radix Scutellariae Baicalensis) were often used in the North to relieve muscles by expelling heat. For moderate cases, Chaihu (Radix Bupleuri Chinensis), Qinghao (Herba Artemisiae Annuae), and Shigao (Gypsum Fibrosum) were often used to clear heat of Tri-jiao Channel and stomach in the South, while Fuling (Poria), Chenpi (Pericarpium Citri Reticulatae), and Dangshen (Radix Codonopsis) were often used to invigorate spleen and remove dampness in the North. For severe cases, spleen invigoration and dampness removal as well as relaxing the bowels and discharging heat were often used in the North. There were certain North-South differences in terms of symptoms, syndrome elements and syndrome distribution of COVID-19, as well as differences in core prescriptions during different periods of the disease. The regional differences in the rules of TCM diagnosis and treatment for COVID-19 should be further considered in the process of optimization and revision of relevant treatment guidance.

Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran.

Background The mortality and morbidity of thrombotic events in patients with coronavirus disease 2019 (COVID-19) are increasing worldwide. The clinical impact of prophylactic anticoagulation regimens among these patients in Iran remains unclear. This study aimed to evaluate the use of prophylactic anticoagulants and outcomes among COVID-19 patients admitted to a tertiary referral hospital. Methodology Patients diagnosed with COVID-19 and hospitalized between March 20 and June 20, 2020, were included in this longitudinal study after obtaining informed consent. Demographic and clinical data were collected from the hospital information system and medical records. Outcomes during this period were also evaluated. The data were entered into the preparation checklist and analyzed using SPSS version 24 software (IBM Corp., Armonk, NY, USA), employing chi-square, Fisher's exact, and Mann-Whitney U tests. Results Of the 831 enrolled patients, 51.9% were female, and 10.6% needed to be admitted to the intensive care unit (ICU). The mean age of the patients was 57.16 ± 17.32 years, and the mortality rate was estimated to be 9.4%. Mortality rates were significantly higher at older ages, in men, patients with ICU admission, severe pulmonary involvement, malignancy, airway obstruction, ischemic heart disease, and previous cerebrovascular accidents. ICU admission and mortality were statistically significantly higher in those who received concurrent prophylactic anticoagulants and aspirin than in other individuals. Conclusions Our study demonstrated that administering prophylactic aspirin with or without anticoagulant agents in COVID-19 patients did not reduce mortality rates or ICU transfers. However, it is worth noting that anticoagulant prescription was associated with a decrease in ICU admissions, which could potentially alleviate the significantly higher mortality rates observed among ICU patients in this study. Further research is needed to explore the potential benefits of anticoagulants in COVID-19 treatment.

COVID-19 Outcomes Among Hematopoietic Cell Transplant and Chimeric Antigen Receptor T-Cell Recipients in the Era of SARS-CoV-2 Omicron Variants and COVID-19 Therapeutics

Recipients of cellular therapies, including hematopoietic cell transplant (HCT) and chimeric antigen receptor T-cell (CART) therapy, are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). There are limited data describing outcomes among patients in the pre- and early post-cellular therapy period during the Omicron era when multiple antiviral therapeutics were widely available. The objective of this study is to describe COVID-19 treatment and outcomes in patients diagnosed with COVID-19 during the pre- or early post-cellular therapy period. This is a single-center retrospective cohort study of adult HCT and CART recipients diagnosed with COVID-19 in the pre- and early post-cellular therapy period who tested positive for COVID-19 at our cancer center between January 1, 2022 and March 1, 2023. Primary outcomes were 30-day COVID-19-related hospitalization and death. A secondary outcome was development of persistent COVID-19, defined by a positive SARS-CoV-2 polymerase chain reaction (PCR) 31 to 90 days after COVID-19 diagnosis. Among 65 patients included, 52 (80%) received at least one COVID-19 therapeutic. The most common treatment after initial COVID-19 diagnosis was nirmatrelvir/ritonavir (29%), followed by monoclonal antibody therapy (26%) and remdesivir (11%). Of the 64 patients with at least 30 days of follow-up, 8 (12%) had at least one COVID-19-related hospitalization and one patient died, though cause of death was not due to COVID-19. Of the 8 patients hospitalized for COVID-19, one had severe disease and 7 had mild or moderate infection. Persistent COVID-19 was observed in 13/65 (20%) patients, with 4 patients requiring additional antiviral therapy. Three pre-cellular therapy patients had delays in receiving cellular therapy due to persistent COVID-19. During the Omicron era, rates of 30-day COVID-19-related hospitalization and death were relatively low in this cohort of pre- and early post-HCT and CART recipients, the majority of whom received treatment with at least one antiviral agent. Persistent COVID-19 occurred in 1 in 5 patients in the peri-cellular therapy period and led to cellular therapy treatment delays in several patients, highlighting the need for new COVID-19 treatment strategies.

The relationship between trust in federal oversight of vaccine safety and willingness to participate in COVID-19 clinical trials: a repeated measures study of Philadelphia residents (September 2021 – March 2023)

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic precipitated an urgent need for clinical trials to discover safe and efficacious treatments. We examined how COVID-19 experiences, clinical trial awareness, and trust in the vaccine safety process were associated with willingness to participate in COVID-19 clinical trials. The objective was to investigate the relationship between trust in federal oversight of vaccine safety and willingness to participate in clinical trials for COVID-19 treatment across four distinct time points over an 18-month period during the COVID-19 pandemic.MethodsWe used four waves of data collected from September 2021 to March 2023 among 582 Philadelphia residents (with a missing data rate of 0.9%). Generalized estimating equations estimated the association between willingness to participate in COVID-19 clinical trials and participants’ trust in the federal government’s oversight of COVID-19 vaccine safety, COVID-19-related variables (COVID-19 related health challenges, history of COVID-19 infection), awareness of clinical trials and how to enroll in them, and sociodemographic characteristics (age, race/ethnicity, sexual orientation, gender, parental status, education, and insurance).ResultsOn average, willingness to participate in a COVID-19 clinical trial was positively associated with greater trust in the federal government’s oversight of vaccine safety [β = 0.34, 95% confidence interval (CI): 0.15–0.53], having COVID-19 (β = 0.40, 95% CI: 0.08–0.73), awareness of clinical trials (β = 0.38, 95% CI: 0.04–0.73), and knowledge of how to enroll (β = 0.83, 95% CI: 0.44–1.23). Among sociodemographic characteristics, race/ethnicity (p = 0.001) and gender (p = 0.018) were identified as predictors for COVID-19 trial willingness.ConclusionWillingness to participate in clinical trials may be bolstered by strengthening the public’s trust in the federal government’s role within vaccine safety oversight, increasing the perceived relevance of clinical trials to individuals’ health and well-being, and offering tailored information to educate diverse communities about ongoing trials and how to enroll in them.

Metformin in COVID-19: a magical role beyond the hyperglycemia

Coronavirus disease-2019 (COVID-19) has emerged as an aggressive viral infection in the last few years. Initially reported in the Wuhan area of the People’s Republic of China, it soon emerged across the globe. Researchers confront a worrying situation to rapidly develop effective strategies to combat this novel infection and its long-term aftereffects. To date, there have been myriad reports ranging from the repurposing of the classical antimalarial drug hydroxychloroquine to several other antiviral and anti-bacterial agents like remdesivir, favipiravir, and most recently azithromycin, which has entered clinical use in many countries for combating COVID-19 infections. Several studies have highlighted the nexus between COVID-19-associated morbidity and diabetes in a wide-ranging class of subjects ranging from pediatric cases to adults and patients with other co-morbidities. Metformin is a mainstay in the treatment of type 2 diabetes (T2D). It is safe, inexpensive, and effective and does more than merely control blood sugar levels. Important metabolites that encourage blood clotting and inflammation are also suppressed by metformin. Pro-inflammatory molecules are linked to obesity and T2D. Both are major risk factors for aggravated COVID-19. These characteristics gave rise to a hypothesis that metformin may find use as an efficacious treatment for COVID-19 especially if it decreases the inflammatory molecules that fuel the COVID-19 virus-induced effects. In this review, we attempt to elucidate the role of classical anti-diabetic medicine metformin in the treatment of COVID-19 infections by highlighting the pharmacological role of this drug during elevated glucose levels and insulin resistance. We examine how COVID-19 has correlations to diabetic physiology and thereby the possibility of repurposing metformin for COVID-19 treatment.

An Age-Specific Crisis Awareness Survey of COVID-19 Vaccines and Treatments Among Healthy Japanese Adults.

Introduction and objectives The spread of coronavirus disease 2019 (COVID-19) has been a worldwide phenomenon. This study conducted a chronological survey of crisis awareness regarding COVID-19 within different age groups. Methods An internet-based survey was performed on healthy Japanese adults to investigate the value of a hypothetical prophylactic vaccine and therapeutic drug for COVID-19 in each age group. In total, 12 groups comprising males and females in six different age groups, leading to a total of 1,200 individuals, were surveyed on a weekly basis. The survey was conducted on Friday of each week commencing from February 14, 2020, to April 10, 2020. At certain times or events such as when the government released major announcements or when there was a rapid increase in the number of infected individuals, a similar survey was conducted on an additional 1,200 individuals per week. Results A total of 12 surveys, including weekly surveys spanning over nine weeks, were conducted; a total of 19,113 samples from 12,254 individuals were obtained. The mean price for a hypothetical prophylactic vaccine was 2876.3 JPY (26.9 USD) at the first survey and was significantly increased to 3357.4 JPY (31.4 USD) for the most recent survey (p<0.0001). The percentage of healthy individuals who were unwilling to pay for a hypothetical therapeutic drug at the onset of COVID-19 symptoms was higher in the young age group than in the elderly groups at all phases, indicating a low level of crisis awareness among some young individuals. On the other hand, the percentage of those willing to pay for more than the standard prophylaxis influenza vaccine remained almost the same in all age groups, and it also increased when COVID-19 infection was widespread. In the sub-analysis, femaleswho have childrenand married individuals tended to answer higher costs for prevention. Conclusions Changes in crisis awareness in all age groups were found to be associated with an increasing familiarity along with an increase in the number of locally infected individuals. Though the percentage of those who will not pay was higher in the young age group than in the elderly age group, the percentage of those who will pay more than the standard costs of influenza vaccine or treatment drugs was the same between each aging group.

Chemical composition combined with network pharmacology and quality markers analysis for the quality evaluation of Qing-fei-da-yuan granules.

Qing-fei-da-yuan granules (QFDYGs) had been proved to be an effective TCM prescription for treating coronavirus disease 2019 (COVID-19), which are composed of a variety of TCMs, and characterized by multiple components, multiple targets and overall regulation. It is meaningful to further study the chemical composition and pharmacology of QFDYGs for quality evaluation. However, due to the complexity of the components of QFDYGs, there are no reliable and simple analytical methods for current quality evaluation. In this work, antipyretic activity assessment of QFDYGs in the LPS-induced New Zealand rabbit model was carried out to verify the efficacy firstly. It was proved that QFDYGs can be used to relieve fever to help preventing or controlling the prevalence of influenza and pneumonia. Subsequently, UHPLC-ESI-QTOF-MS/MS combined with network pharmacology, quality markers and fingerprint analysis were used to establish the quality control condition. The chemical compositions were analyzed by UHPLC-ESI-QTOF-MS/MS, and 79 of them were identified, such as arecoline, mangiferin, paeoniflorin, etc. Then, the network pharmacology strategy based on 45 candidate components (CCs) in conjunction with influenza and pneumonia diseases was employed to screen the potential active ingredients. According to the drug-CCs-genes-diseases (D-CCs-G-D) networks, baicalein, honokiol, baicalin, paeoniflorin, saikosaponin A, glycyrrhizic acid and hesperidin were selected as quality markers. And a method for content determination of the 7 quality markers was established by optimizing extraction methods, chromatographic conditions and methodological verification. Finally, the quality of 15 batches of QFDYGs was evaluated by using the 7 quality markers combined with fingerprints and principal component analysis (PCA). The analyzed results showed that baicalin, paeoniflorin, glycyrrhizic acid and hesperidin were the high content and stable quality markers. QFDYGs were characterized by overall consistency and individual ingredient differences among the 15 batches. Our quality evaluation study will provide reference for the further development and research of QFDYGs.

Sotrovimab in the treatment of coronavirus disease-2019 (COVID-19): a systematic review and meta-analysis of randomized clinical trials.

This study was carried out to verify the evidence regarding the effectiveness and safety of sotrovimab in patients with COVID-19. This is a systematic review of randomized clinical trials retrieved from the PubMed, Embase, Scopus, Lilacs, and Cochrane Library databases. The risk of bias was measured using the Cochrane Risk and Bias Checklist (RoB 2). For the meta-analysis, RStudio Version 2024.04.2 software was used. The certainty of evidence was assessed using GRADE. The study protocol was registered in PROSPERO (CRD42022355786). A total of 1893 studies were identified and four were included in the study. The total population consisted of 5470 patients with COVID-19, 1921 (35%) in the sotrovimab group and 3549 (65%) in the control group (placebo or BRII-196 + BRII-198 or casirivimab + imdevimab or bamlanivimab + etesevimab, administered in a similar way to sotrovimab, in a single dose with a 60-min intravenous infusion). For the effectiveness outcome, three studies presented low risk and one high risk of bias, while for safety all presented high risk of bias. The meta-analysis showed no significant difference between the sotrovimab and control groups in terms of hospitalization rates (95% confidence interval (CI) - 2.10-0.51; p = 0 > 0.05), use of invasive mechanical ventilation (95% CI - 2.78-0.65; p = 0.35) and mortality (95% CI - 0.92-0.59; p = 0.39). However, sensitivity analysis showed that sotrovimab may be effective in reducing hospitalization rates compared to the control (IV = - 1.57; 95% CI - 2.41-0.73; p = 0.99). The use of sotrovimab in the treatment of patients with COVID-19 had no significant impact on mortality and need for mechanical ventilation and did not appear to be safer compared to controls. However, there was evidence of effectiveness in reducing the rate of hospitalization, although the certainty of the evidence is moderate and the risk of bias is high.

Construction of a multi-tissue compound-target interaction network of Qingfei Paidu decoction in COVID-19 treatment based on deep learning and transcriptomic analysis.

The Qingfei Paidu decoction (QFPDD) is a widely acclaimed therapeutic formula employed nationwide for the clinical management of coronavirus disease 2019 (COVID-19). QFPDD exerts a synergistic therapeutic effect, characterized by its multi-component, multi-target, and multi-pathway action. However, the intricate interactions among the ingredients and targets within QFPDD and their systematic effects in multiple tissues remain undetermined. To address this, we qualitatively characterized the chemical components of QFPDD. We integrated multi-tissue transcriptomic analysis with GraphDTA, a deep learning model, to screen for potential compound-target interactions of QFPDD in multiple tissues. We predicted 13 key active compounds, 127 potential targets and 27 pathways associated with QFPDD across six different tissues. Notably, oleanolic acid-AXL exhibited leading affinity in the heart, blood, and liver. Molecular docking and molecular dynamics simulation confirmed their strong binding affinity. The robust interaction between oleanolic acid and the AXL receptor suggests that AXL is a promising target for developing clinical intervention strategies. Through the construction of a multi-tissue compound-target interaction network, our study further elucidated the mechanisms through which QFPDD effectively combats COVID-19 in multiple tissues. Our work also establishes a framework for future investigations into the systemic effects of other Traditional Chinese Medicine (TCM) formulas in disease treatment.

Exploring the therapeutic potential of Thai medicinal plants: in vitro screening and in silico docking of phytoconstituents for novel anti-SARS-CoV-2 agents

BackgroundThe high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), has triggered global health and economic concerns. The absence of specific antiviral treatments and the side effects of repurposed drugs present persistent challenges. This study explored a promising antiviral herbal extract against SARS-CoV-2 from selected Thai medicinal plants based on in vitro efficacy and evaluated its antiviral lead compounds by molecular docking.MethodsTwenty-two different ethanolic-aqueous crude extracts (CEs) were rapidly screened for their potential activity against porcine epidemic diarrhea virus (PEDV) as a surrogate using a plaque reduction assay. Extracts achieving ≥ 70% anti-PEDV efficacy proceeded to the anti-SARS-CoV-2 activity test using a 50% tissue culture infectious dose method in Vero E6 cells. Molnupiravir and extract-free media served as positive and negative controls, respectively. Potent CEs underwent water/ethyl acetate fractionation to enhance antiviral efficacy, and the fractions were tested for anti-SARS-CoV-2 performance. The fraction with the highest antiviral potency was identified using liquid chromatography–high-resolution mass spectrometry (LC–HRMS). Molecular docking analyses of these compounds against the main protease (Mpro) of SARS-CoV-2 (6LU7) were performed to identify antiviral lead molecules. The top three hits were further evaluated for their conformational stability in the docked complex using molecular dynamics (MD) simulation.ResultsThe water fraction of mulberry (Morus alba Linn.) leaf CE (WF-MLCE) exhibited the most potent anti-SARS-CoV-2 efficacy with low cytotoxicity profile (CC50 of ~ 0.7 mg/mL), achieving 99.92% in pre-entry mode and 99.88% in postinfection treatment mode at 0.25 mg/mL. Flavonoids and conjugates were the predominant compounds identified in WF-MLCE. Molecular docking scores of several flavonoids against SARS-CoV-2 Mpro demonstrated their superior antiviral potency compared to molnupiravir. Remarkably, myricetin-3-O-β-D-galactopyranoside, maragrol B, and quercetin 3-O-robinobioside exhibited binding energies of ~ − 9 kcal/mol. The stability of each ligand–protein complex of these compounds with the Mpro system showed stability during MD simulation. These three molecules were pronounced as antiviral leads of WF-MLCE. Given the low cytotoxicity and high antiviral potency of WF-MLCE, it holds promise as a candidate for future therapeutic development for COVID-19 treatment, especially considering its economic and pharmacological advantages.

Real-world effectiveness of sotrovimab in preventing hospitalization and mortality in high-risk patients with COVID-19 in the United States: A cohort study from the Mayo Clinic electronic health records.

To describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes. This observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts. We included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001). There was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.