Search

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting. The panel conducted a detailed review of the literature and eventual press releases from randomized clinical trials for each possible available treatment. Inductive PubMed search waws performed for publications relevant to the topic, including all clinical trials conducted. The result was a flowchart with treatment indications for patients with COVID-19. After 6 months of a pandemic situation and before a possible second coronavirus wave descends on Europe, it is important to evaluate which drugs proved to be effective while also considering that results from many randomized clinical trials are still awaited. Indeed, among treatments for COVID-19, only glucocorticoids have resulted in an association with a significant decrease in mortality in published randomized controlled trials. New therapeutic strategies are urgently needed. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor the usage of COVID-19 therapeutics in hospital and community settings and to inform stewardship. Three antiviral therapies—nirmatrelvir plus ritonavir (Paxlovid®), remdesivir (Veklury®), and molnupiravir (Lagevrio®)—and two neutralising monoclonal antibody therapies (nMAbs)—sotrovimab (Xevudy®) and casirivimab with imdevimab (Ronapreve®)—were in use in England between July 2020 and April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) Report 2022 to 2023 also discusses the epidemiological surveillance of these five directly acting antiviral COVID-19 therapeutics' use in England between 2022 and 2023. [ABSTRACT FROM AUTHOR]

Background: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. Methods: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. Results: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8–16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. Conclusion: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented. Highlights: The highlights of the paper are: 1. High-dose corticosteroid can shorten the recovery time of body temperature. 2. High-dose corticosteroid can better reduce inflammatory factors (CRP IL-6). 3. Oral hormones in discharged patients with severe COVID-19 pneumonia are beneficial. 4. Initial dosage and course of corticosteroid might be varied case by case. [ABSTRACT FROM AUTHOR]

We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia in four severely immunocompromised patients currently being treated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative in all patients. SARS-CoV-2 infection was confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine COVID-19 convalescent plasma was administered with complete recovery in all patients. [ABSTRACT FROM AUTHOR]

Ozone therapy (OT), a medical procedure, has been showing good results during the coronavirus disease (COVID-19). We aimed to build an evidence and gaps map (EGM) of OT in the COVID-19 ranking the articles found according to levels of evidence and outcomes. The EGM brings bubbles of different sizes and different colors according to the articles. The OT intervention used was major or minor autohemotherapy, rectal insufflation and ozonized saline solution. EGM was based on 13 clinical studies using OT for COVID-19 involving a total of 271 patients. We found 30 outcomes related to OT in COVID-19. Our EGM divided the outcomes into six groups: 1-clinical improvement; 2-hospitalization; 3-inflammatory, thromboembolic, infectious, or metabolic markers; 4-radiological aspects, 5-viral infection and 6-adverse events. Major autohemotherapy was present in 19 outcomes, followed by rectal insufflation. Improvement in clinical symptoms of COVID-19, improvement of respiratory function, improvement of oxygen saturation, reduction in hospital internment, decrease in C-reactive protein, decrease in ferritin, decrease in lactate dehydrogenase, decrease in interleukin 6, decrease in D-dimer, radiological improvement of lung lesions and absence of reported adverse events were related in the papers. The most commonly used concentrations of OT in major autohemotherapy and in rectal insufflation were 40 µg/mL and 35 µg/mL, respectively. Here, we bring the first EGM showing the efficacy and safety of OT in the treatment of COVID-19. OT can be used as integrative medical therapy in COVID-19 at a low cost and improve the health conditions of the patients. [ABSTRACT FROM AUTHOR]

India's pharmaceutical sector has been one of the largest manufacturers of generic drugs globally. During the pandemic, most countries were dependent on imports of generic drugs from India. However, India has been relying on resources from China for Active Pharmaceutical Ingredients (APIs) which are the raw material for preparing generic drugs. We considered, in our analysis, branded product groups of Paracetamol and Amoxicillin due to their extensive use in the treatment of COVID-19. From a thorough market analysis of both the drugs, we conclude that firms have a monopoly over their brands but compete within the same product group and operate in their respective market under varying prices within certain bandwidths which resembles the feature of monopolistic competitive market. We have introduced compensating function a la Helpman (1981) in the pharmaceutical goods market with the assumption that an 'ideal product' exists among the pharmaceutical goods. Given the framework, this paper explores a general equilibrium model set in a monopolistic competitive product market for branded drugs. We concluded through our propositions that expanding the pharmaceutical sector will increase the employment of unskilled labor under no capacity constraint. We will observe an increase in wages of unskilled labor only under full employment conditions wherein we would observe that the expansion of pharmaceutical good will increase wages in the unskilled labor market. However we obtain an intriguing result wherein we obtain that despite instances of limiting trade dependence on China through implementation of policies like 'Aatmanirbhar Bharat' and 'profit linked incentive schemes', yet to maintain the status quo in the global market for generic drugs, India's dependence on China would increase, owing to API imports due to the pandemic crisis. While India can grab the opportunity in the form of increased demand for pharmaceutical goods to increase the employment level of the economy but this improvement in welfare is also dependent on the degree of dependency of API India has on China. The Indian government has recognized the same through the incorporation of 'Covid-Suraksha' and PLI schemes to minimize import dependency, and accelerate the development of APIs and the production of indigenous drugs. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS‐CoV‐2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro‐ or macro‐vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID‐19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life‐threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID‐19‐induced hypercoagulable state and the use of anticoagulants to treat SARS‐CoV‐2 infections in different patient groups, as well as their pros and cons. [ABSTRACT FROM AUTHOR]

Background: During the process of the treatment of COVID-19 hospitalized patients, physicians still face a lot of unknowns and problems. Despite the application of the treatment protocol, it is still unknown why the medical status of a certain number of patients worsens and ends with death. Many factors were analyzed for the prediction of the clinical outcome of the patients using different methods. The aim of this paper was to develop a prediction model based on initial laboratory blood test results, accompanying comorbidities, and demographics to help physicians to better understand the medical state of patients with respect to possible clinical outcomes using neural networks, hypothesis testing, and confidence intervals. Methods: The research had retrospective-prospective, descriptive, and analytical character. As inputs for this research, 12 components of laboratory blood test results, six accompanying comorbidities, and demographics (age and gender) data were collected from hospital information system in Sarajevo for each patient from a sample of 634 hospitalized patients. Clinical outcome of the hospitalized patients, survival or death, was recorded 30 days after admission to the hospital. The prediction model was designed using a neural network. In addition, formal hypothesis tests were performed to investigate whether there were significant differences in laboratory blood test results and age between patients who died and those who survived, including the construction of 95% confidence intervals. Results: In this paper, 11 neural networks were developed with different threshold values to determine the optimal neural network with the highest prediction performance. The performances of the neural networks were evaluated by accuracy, precision, sensitivity, and specificity. Optimal neural network model evaluation metrics are: accuracy = 87.78%, precision = 96.37%, sensitivity = 90.07%, and specificity = 62.16%. Significantly higher values (P < 0.05) of blood laboratory result components and age were detected in patients who died. Conclusion: Optimal neural network model, results of hypothesis tests, and confidence intervals could help to predict, analyze, and better understand the medical state of COVID-19 hospitalized patients and thus reduce the mortality rate. [ABSTRACT FROM AUTHOR]

Vaccination is an important tool in the fight against the COVID-19 pandemic in patients with haematologic malignancies. The paper provides an analysis of the course of breakthrough SARS-CoV-2 infection in a group of vaccinated patients with haematological malignancy and a comparison with a historical cohort of 96 non-vaccinated patients with haematologic malignancies and bone marrow failure syndromes (two patients) in the treatment of COVID-19. A severe or critical course of COVID-19 was significantly less frequent in the group of vaccinated patients (10.2% vs. 31.4%, p = 0.003). The need for hospitalisation due to COVID-19 was significantly lower in vaccinated patients (27.1% vs. 72.6%, p < 0.0001) and the duration of hospitalisation was significantly shorter (10 vs. 14 days, p = 0.045). Vaccinated patients were insignificantly less likely to require oxygen therapy during infection. COVID-19 mortality was significantly higher in non-vaccinated patients (15.6% vs. 5.1%, p = 0.047). The paper demonstrated a significant positive effect of vaccination against COVID-19 on a less severe clinical course of infection, lower need for hospitalisation and mortality. However, the results need to be evaluated even in the context of new antivirals and monoclonal antibodies against SARS-CoV-2 or virus mutations with different biological behaviour. [ABSTRACT FROM AUTHOR]

The purpose of this review was to conduct a comparative assessment of the concepts of therapy for pediatric patients with COVID-19 in the framework of global clinical practice. A structural analysis of the range of drugs and treatment strategies in the context of etiotropic, pathogenetic, and symptomatic therapy has shown that in the global context and in real clinical practice, the etiotropic-pathogenetic approach based on information about the effectiveness of individual medical technologies prevails today. It has been established that eight international nonproprietary/grouping names are present in international practice as means of etiotropic therapy for pediatric patients with COVID-19, and 18 positions are used for pathogenetic therapy. In terms of frequency of occurrence, the leading positions are occupied by remdesivir and the combination of nirmatrelvir with ritonavir, as well as dexamethasone and tocilizumab. The paper emphasizes the relevance of research in the field of evaluating the effectiveness of individual treatment regimens as well as the analysis of the delayed consequences of pathology suffered in childhood under the conditions of using various approaches to pharmacotherapy. [ABSTRACT FROM AUTHOR]

Symmetry is a key part of the study of basic forces and particles, as well as the creation of mathematical models that help scientists in various scientific disciplines understand complex events. Scientists can figure out what a system is made of and how it works by looking at its symmetry. They can then use this information to make predictions and create new materials and technologies. Humanity has conquered many once-fatal diseases due to medical research and technological advancements. Although this progress is encouraging, there are still a great many areas that require continual human efforts. An effort is made in this article to choose the best treatment strategy to completely manage the pandemic of COVID-19 under conjunctive complex fuzzy knowledge. In this paper, the concept of conjunctive complex fuzzy relations is presented and numerous set theoretical aspects of this phenomenon are established. The investigation of this ideology is further expanded to describe different sorts of essential structural conjunctive complex fuzzy relations. Matrix and graphical representations of the formation of these newly specified relations are also provided. Moreover, this concept has been successfully employed to provide a therapy strategy for a rapid recovery from COVID-19. Furthermore, a comparative analysis is conducted to demonstrate the validity and applicability of the suggested approaches compared to existing methods. [ABSTRACT FROM AUTHOR]

Several studies have been directed to find scalable, swift, accurate, and cost‐effective strategies for detecting, monitoring, and treating coronavirus disease 2019 (COVID‐19). Indeed, the lack of a fast and practical method for detecting the infected regions makes decision‐making challenging to combat the critical pandemic‐struck situations. The probable 'wrong', or rather inadequate, decisions not only have a boomerang effect on the economy but also can lead to an increase in the number of infected individuals, degree of hospitalization, and death counts. Although the current clinical methods are effective, they are costly, time‐consuming, and, more particularly, inadequate because of the virus's mutation patterns. In addition, contamination of biomedical wastes with the COVID‐19 virus is a matter of grave concern. Therefore, there is a perpetual need for novel methodologies to delineate the contaminated regions and determine whether those viruses contaminate the wastewater. Although several review papers have been recently published to discuss those concerns, there is a lack of a comprehensive survey of the detection and treatment of the COVID‐19 virus in aqueous media. Herein, we review techniques available as spreading signifiers for detecting the COVID‐19 virus in water resources and wastewater. We classify and integrate techniques into wastewater, sewage, and sludge detection and monitoring. Treatment of COVID‐19‐contaminated wastewater is discussed by classifying and ranking the methodologies nurtured from nanotechnology, including nanoparticle‐based biosensors used in the detection and nanotechnology‐based filtration systems for the removal of COVID‐19 from wastewater. We also highlight the compilation of the detection methodologies in contaminated aqueous media and provide insight into the challenges associated with treating COVID‐19‐contaminated wastewater. The article concludes that international and robust guidelines for virus/bacteria treatment in wastewater are urgently needed to protect the environment and public health, where nanotechnology plays a key role. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has given rise to all types of beliefs, theories, and explanations, whether scientific, religious, or conspiratorial. At the beginning of the pandemic, science did not yet have a medicinal product for this new disease, and alternative medicines offering "miracle cures" were acclaimed by some citizens looking for an effective treatment for COVID-19. This article aims to study a specific "miracle cure", namely, chlorine dioxide, a bleaching agent for textiles or paper that also has disinfectant properties (water, surfaces). The dissemination of information about chlorine dioxide to French-speaking people on the social network Twitter from 1 December 2019 to 30 November 2021 is analyzed using a graph network. The results show that messages promoting misinformation, even if they are likely to be quantitatively less numerous, spread more widely than those based on more reliable information. In addition, this article shows that chlorine dioxide was promoted as an effective cure by medical doctors and peer-reviewed articles, which consequently increased the dissemination of this belief in the social space. Consequently, the process of misinformation entered the sphere of scientific controversy. The boundary between science and misinformation is becoming blurred to the point that it is no longer possible until proven otherwise to call chlorine dioxide a "false miracle cure" but a controversial treatment against COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Ephedra herbs are the only extant genus in its family, Ephedraceae, and order, Ephedrales. It has been prescribed in traditional medicine for improving headaches and respiratory infections. On the other hand, because the coronavirus disease 2019 (COVID-19) causes respiratory problems and COVID-19 pandemic is the most widespread outbreak that has affected humanity in the last century, the current review aims using literature search to investigate the effects of the Ephedra herbs compounds on COVID-19 to supply a reference for its clinical application in the inhibition and remedy of COVID-19. Materials and Methods: This review was performed using articles published in various databases, including Web of Science, PubMed, Scopus, and Google Scholar, without a time limit. For this paper, the following keywords were used: "Ephedra", "coronavirus disease 2019", "COVID-19", "Severe acute respiratory syndrome coronavirus 2" or "SARS CoV 2". Results: The results of this review show that the Ephedra herbs have effectiveness on COVID-19 and its compounds can bind to angiotensin-converting enzyme 2 (ACE2) with a high affinity and act as a blocker and prevent the binding of the virus. Conclusion: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Patients with coronavirus disease 2019 (COVID-19) undergoing maintenance hemodialysis have a poor prognosis and limited treatment options. Methods: This paper outlines the impact of COVID-19, its treatment, and the efficacy of vaccines in Japanese patients undergoing hemodialysis with a review of the literature. Results: Patients undergoing dialysis in dialysis facilities are at greater risk of exposure to severe acute respiratory syndrome coronavirus 2 than the general population due to limited isolation capabilities. Therefore, vaccines are expected to be effective for patients undergoing dialysis. In addition, effective use of available medications is important because treatment options are limited. Conclusions: Efforts should be made to prevent the spread of the infection to high-risk patients undergoing dialysis while ensuring the effective use of vaccines. [ABSTRACT FROM AUTHOR]

This paper explores a dual inhibition of main protease (Mpro) and nonstructural protein 10/nonstructural protein 16 (NSP16) methyltransferase complex as the key targets for COVID-19 therapy. These are based on the new Schiff-base ligand that was obtained from the condensation of (4-chloro-3-methyl phenyl) hydrazine with 2-pyridine-carboxaldehyde and its novel Schiff-base metal complexes. These include Ni(II), Pd(II), Pt(II), Zn(II), and Hg(II). The newly synthesized compounds have been characterized using FT-IR, 1H NMR, 13C NMR, and elemental analysis. The results suggested that the Schiff-base ligand is coordinated as a bidentate ligand through the nitrogen atoms of the azomethine group and pyridyl ring. In addition, the biological activity of the prepared complexes was examined against Pseudomonas aeruginosa and Staphylococcus aureus, and the results showed that the Zn(II) complex has the highest activity compared with other compounds. The active sites were found by looking at the molecular electrostatic potential (MEP) maps of the above ligands and complexes. The activity of the compound and its Ni(II) and Zn(II) complexes against Mpro and NSP10/ NSP16 was investigated using a molecular docking approach. They showed excellent binding energies ranging from −5.9 to −7.2 kcal/mol and −5.8 to −7.2 for Mpro and NSP16, respectively. All conformers of the metal complexes were docked with the active site of the NSP16 receptor, showing a binding affinity of 100%. According to our knowledge, this was the first report of these metal complexes as dual inhibitors for Mpro and NSP16 of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24-48 h of their test result.Methods: A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24-48 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology.Results: Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached.Conclusions: This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions.Trial Registration: PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22 . 26/03/2020 ISRCTN registry: ISRCTN86534580 . 20/03/2020 REC number: 20/SC/058 IRAS number: 281958. [ABSTRACT FROM AUTHOR]

Background: Numerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques. Methods: We provide a detailed look at the challenges and solutions for model development, describing the process that used extensive simulations to enable us to finalize the analysis plan. This includes establishing prior distribution assumptions, assessing and improving model convergence under different study composition scenarios, and assessing whether we can extend the model to accommodate multi-site RCTs and evaluate heterogeneous treatment effects. In addition, we recognized that we would need to assess our model for goodness-of-fit, so we explored an approach that used posterior predictive checking. Lastly, given the urgency of the research in the context of evolving pandemic, we were committed to frequent monitoring of the data to assess efficacy, and we set Bayesian monitoring rules calibrated for type 1 error rate and power. Results: The primary outcome is an 11-point ordinal scale. We present the operating characteristics of the proposed cumulative proportional odds model for estimating treatment effectiveness. The model can estimate the treatment's effect under enormous uncertainties in study design. We investigate to what degree the proportional odds assumption has to be violated to render the model inaccurate. We demonstrate the flexibility of a Bayesian monitoring approach by performing frequent interim analyses without increasing the probability of erroneous conclusions. Conclusion: This paper describes a translatable framework using simulation to support the design of prospective IPD meta-analyses. [ABSTRACT FROM AUTHOR]

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19. [ABSTRACT FROM AUTHOR]

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic is known to affect several body organs, including the liver. This results from several factors such as direct effect of SARS-CoV-2 on the liver, side effects of drug therapy and pre-existing liver diseases. Drug-induced liver injury can result from a range of drugs used in the treatment of COVID-19 such as antiviral drugs, anti-inflammatory drugs, antibiotics, herbal medications and vaccines. Metabolism of most drugs occurs in the liver, and this leaves the liver at risk of medication-induced liver damage. Being among pathologies from the disease, COVID-19 liver injury presents with abnormally high liver-related enzymes, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphate (ALP), and gamma-glutamyl transferase. It is reversible, generally not severe and occurs more mildly in children. However, COVID-19-associated liver injury is worsened by chronic liver diseases and vice versa. There is a high risk of abnormal ALT and AST, in-hospital liver injury and prolonged SARS-CoV-2 shedding in COVID-19 patients with previously existing metabolic-associated fatty liver disease. COVID-19-associated liver injury also appears to be severe and significantly associated with life-threatening COVID-19 and mortality in persons with a history of liver transplant. Where necessary, only supportive management is usually indicated. This paper evaluates the aetiology, clinical and laboratory features, occurrence and management of COVID-19-associated liver injury. It also elaborated on the role of drug therapy in the development of COVID-19 liver injury. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) continues to have a negative impact on healthcare systems around the world, though the vaccines have been developed and national vaccination coverage rate is steadily increasing. At the current stage, automatically segmenting the lung infection area from CT images is essential for the diagnosis and treatment of COVID-19. Thanks to the development of deep learning technology, some deep learning solutions for lung infection segmentation have been proposed. However, due to the scattered distribution, complex background interference and blurred boundaries, the accuracy and completeness of the existing models are still unsatisfactory. To this end, we propose a boundary guided semantic learning network (BSNet) in this paper. On the one hand, the dual-branch semantic enhancement module that combines the top-level semantic preservation and progressive semantic integration is designed to model the complementary relationship between different high-level features, thereby promoting the generation of more complete segmentation results. On the other hand, the mirror-symmetric boundary guidance module is proposed to accurately detect the boundaries of the lesion regions in a mirror-symmetric way. Experiments on the publicly available dataset demonstrate that our BSNet outperforms the existing state-of-the-art competitors and achieves a real-time inference speed of 44 FPS. The code and results of our BSNet can be found from the link of https://github.com/rmcong/BSNet. [ABSTRACT FROM AUTHOR]

Cases of the COVID-19 pandemic have spread throughout the world and caused a high mortality rate. This virus is self-limiting, so the healing process is related to the immune system. One of the medical therapies given to hospitalized COVID-19 patients is vitamin D-based therapy to boost the immune system against the COVID-19 virus. This paper aimed to determine the effectiveness of vitamin D-based therapy to reduce the clinical impact on COVID-19 patients. The clinical impacts observed in this systematic review were the length of hospital stay, length in the ICU stay, cure rate, severity, mortality rate, and signs of inflammation. A literature search was carried out on the Scopus, Sciencedirect, and PUBMED databases. Search articles using the keyword vitamin D therapy in COVID-19 patients. The final result of the search found 6 articles that met the specified inclusion and exclusion criteria. Vitamin D in its active form (1,25(OH)2D3) can enhance chemotaxis, phagocytic response, and production of antimicrobials such as cathelicidin from macrophages as a series of innate immune responses. Administration of vitamin D-based therapy can also reduce the severity, decrease pro-inflammatory cytokines, and mortality in COVID-19 patients. The paper shows that vitamin D-based therapy can reduce the clinical impact in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Community is directly responsible for implementing the policy measures against public emergencies such as extreme weather, earthquake, flash flood and pandemic diseases. Summarizing the experience at the urban community level can help promote the global emergency management. This paper, from the perspective of COVID-19 prevention and control, selects three communities with different features to explore an effective response system for public emergency management at the urban community level. It demonstrates that based on a centralized leadership, the multi-level governance (MLG) network combined with information technology has mobilized their participation in combating COVID-19 and ensured the effective and timely response to the public emergencies, which blocked the spread of epidemic to the greatest extent, proving worthy of being promoted as one of the Chinese approaches and Chinese wisdom. [ABSTRACT FROM AUTHOR]

The sudden outbreak of the novel coronavirus pandemic in 2019 disrupted the normal order of life and work, and the virus is still a major threat prevailing the globe. Confronted with the unknown virus, citizens have been following government policies of COVID-19 treatment and containment, and actively improving their immunity through physical activity (PA). This paper is concerned with ways to guide or promote people's willingness to exercise, one of the most effective means to boost immunity. Based on the "attitude–intention" correlation defined in the theory of planned behaviour (TPB), this study, by synchronizing online data about workouts, explores the influence of people's attitudes towards PA behaviour in promoting their intentions to engage in such behaviours as a means to fight the pandemic. In addition, the attitudes towards the use of sports apps and the epidemic are also reckoned with to investigate influencing factors promoting physical activity during the lockdown. The results of the study have been derived from the data of 1223 valid questionnaires, which are subjected to hierarchical regression analysis. Attitudes towards exercise and the use of sports apps are proven to have a significant impact on PA intentions, and the two variables are in direct proportion, with more positive attitudes leading to higher intentions; in contrast, attitudes towards the epidemic do not exhibit an obvious effect. In this light, it is advisable that when clinicians treat COVID-19 patients and medical departments respond to the epidemic, they actively make affirmative influences on peoples' attitudes towards exercise and formulate appropriate exercise plans based on indicators detected and recorded by sports apps such as vital capacity, heart rate, respiratory index and self-perceived intensity to help them face the risk of the epidemic with more confidence. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies' integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF. [ABSTRACT FROM AUTHOR]

Medical facility equality is a critical metric for determining equal access to medical care. Their spatial distribution is important for effective pandemic treatment and daily prevention in cities. This paper used the Kernel Density Two-Step Floating Catchment Area (KD2SFCA) and shortest distance methods to calculate the accessibility of designated COVID-19 Fangcang hospitals and fever clinics in the Wuhan Metropolitan Development Zone. Their equality was evaluated by the Gini coefficient and Lorentz curve. Several results were obtained: (1) The facilities' accessibility declines radial from the central to peripheral areas. (2) Most of the demand points in the study area can reach the medical facilities for COVID-19 pandemic treatment within 60 minutes. (3) For the spatial distribution of these facilities, the equality evaluated for different time thresholds differed significantly, with long time thresholds having better equality than for short time thresholds. (4) While the distances distribution of fever clinics is balanced, the equality gap in various areas remains enormous when considering population distribution. Suggestions for optimizing the spatial distribution of pandemic treatment medical facilities in Wuhan are proposed, and which will serve as references for the planning of Wuhan's pandemic medical facilities in the future. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented threat to public health. The pandemic has been sweeping the globe, impacting more than 200 countries, with more outbreaks still lurking on the horizon. At the time of the writing, no approved drugs or vaccines are available to treat COVID-19 patients, prompting an urgent need to decipher mechanisms underlying the pathogenesis and develop curative treatments. To fight COVID-19, researchers around the world have provided specific tools and molecular information for SARS-CoV-2. These pieces of information can be integrated to aid computational investigations and facilitate clinical research. This paper reviews current knowledge, the current status of drug development and various resources for key steps toward effective treatment of COVID-19, including the phylogenetic characteristics, genomic conservation and interaction data. The final goal of this paper is to provide information that may be utilized in bioinformatics approaches and aid target prioritization and drug repurposing. Several SARS-CoV-2-related tools/databases were reviewed, and a web-portal named OverCOVID (http://bis.zju.edu.cn/overcovid/) is constructed to provide a detailed interpretation of SARS-CoV-2 basics and share a collection of resources that may contribute to therapeutic advances. These information could improve researchers' understanding of SARS-CoV-2 and help to accelerate the development of new antiviral treatments. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a pandemic whose adverse effects have been felt all over the world. As of August 2022, reports indicated that over 500 million people in the world had been infected and the number of rising deaths from the disease were slightly above 6.4 million. New variants of the causative agent, SARS-CoV-2 are emanating now and then and some are more efficacious and harder to manage. SARSCoV-2 main protease (Mpro) has essential functions in viral gene expression and replication through proteolytic cleavage of polyproteins. Search for SARS-CoV-2 Mpro inhibitors is a vital step in the treatment and management of COVID-19. In this study, we investigated whether alkaloids with antiviral and myriad other bioactivities from the genus Lycoris can act as SARS-CoV-2 Mpro inhibitors. We conducted a computer-aided drug design study through screening optimal ligands for SARS-CoV-2 Mpro from a list of over 150 Lycoris alkaloids created from online databases such as ChEMBL, PubChem, ChemSpider, and published journal papers. The In silico study involved molecular docking of Lycoris alkaloids to SARS-CoV-2 Mpro active site, absorption, distribution, metabolism, elimination and toxicity (ADMET) screening and finally molecular dynamic (MD) simulations of the most promising ligand-SARS-CoV-2 Mpro complexes. The study identified 3,11-dimethoxy-lycoramine, narwedine, O-demethyllycoramine and epilycoramine as drug-like and lead-like Lycoris alkaloids with favorable ADMET properties and are very likely to have an inhibition activity on SARSCoV-2 Mpro and may become potential drug candidates. [ABSTRACT FROM AUTHOR]

CCOVID-19 was first reported in late 2019 in Wuhan, China, and spread throughout the world like a pandemic. The population all over the world used lots of medicinal plants for prevention purposes. India has been blessed with cultural wisdom. Social health practices across the country have been utilizing integrative treatments to fight against mild fever and cold flu-like infections. Herbal and Ayurveda medicines have shown their impact on treating such infections in the early stages. The impact of herbal medicines on Covid infection is quite evident and several drug tests and trials have proved its worth of it in treating mild to severe infections. The majority of these plants are used to treat respiratory diseases having the same signs and symptoms as coronavirus symptoms or other flu infections. Our body can fight infections only when immunity is strong and for that herbal drugs as immunomodulators work well. It has worked in boosting the immunity of the patients and normal people to fight against Corona. The paper analyzes such research studies on Covid-19 treatment by herbal medicines. It makes a point that herbal medicine-based treatments and social health practices will play a complementary role in managing Covid-19 and Post-Covid health emergencies. New-Normal social ethics will evolve through such an integrative social health culture. [ABSTRACT FROM AUTHOR]

Background: A global pandemic has been declared for coronavirus disease 2019 (COVID-19), which has serious impacts on human health and healthcare systems in the affected areas, including Vietnam. None of the previous studies have a framework to provide summary statistics of the virus variants and assess the severity associated with virus proteins and host cells in COVID-19 patients in Vietnam.Method: In this paper, we comprehensively investigated SARS-CoV-2 variants and immune responses in COVID-19 patients. We provided summary statistics of target sequences of SARS-CoV-2 in Vietnam and other countries for data scientists to use in downstream analysis for therapeutic targets. For host cells, we proposed a predictive model of the severity of COVID-19 based on public datasets of hospitalization status in Vietnam, incorporating a polygenic risk score. This score uses immunogenic SNP biomarkers as indicators of COVID-19 severity.Result: We identified that the Delta variant of SARS-CoV-2 is most prevalent in southern areas of Vietnam and it is different from other areas in the world using various data sources. Our predictive models of COVID-19 severity had high accuracy (Random Forest AUC = 0.81, Elastic Net AUC = 0.7, and SVM AUC = 0.69) and showed that the use of polygenic risk scores increased the models' predictive capabilities.Conclusion: We provided a comprehensive analysis for COVID-19 severity in Vietnam. This investigation is not only helpful for COVID-19 treatment in therapeutic target studies, but also could influence further research on the disease progression and personalized clinical outcomes. [ABSTRACT FROM AUTHOR]

Gaming activities have conferred numerous benefits during the COVID-19 pandemic. However, some individuals may be at greater risk of problem gaming due to disruption to adaptive routines, increased anxiety and/or depression, and social isolation. This paper presents a summary of 2019–2021 service data from specialist addiction centers in Germany, Switzerland, Japan, and the United Kingdom. Treatment demand for gaming disorder has exceeded service capacity during the pandemic, with significant service access issues. These data highlight the need for adaptability of gaming disorder services and greater resources and funding to respond effectively in future public health crises. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 19 (COVID-19), a disease that has affected more than 500 million people worldwide since the end of 2019. Due to its high complications and death rates, there is still a need to find the best therapy for SARS-CoV-2 infection. The dysregulation of the inflammatory response in COVID-19 plays a very important role in disease progression. It has been observed that abnormal activity of Nuclear Factor kappa B (NF-κB) is directly associated with, inter alia, increased synthesis of proinflammatory factors. Therefore, this review paper focuses on the functions of NF-κB in the development of SARS-CoV-2 infection and potential application of NF-κB inhibitors in COVID-19 immunotherapy. A comprehensive literature search was performed using the MEDLINE/PubMed database. In the current review, it is highlighted that NF-κB plays important functions in the modulation of an adaptive inflammatory response, including inducing the expression of proinflammatory genes. Increased activation of NF-κB in SARS-CoV-2 infection was observed. The association between NF-κB activation and the expression of SARS-CoV-2 structural and non-structural proteins were also reported. It was observed that modulation of NF-κB using, e.g., traditional Chinese medicine or glucocorticosteroids resulted in decreased synthesis of proinflammatory factors caused by SARS-CoV-2 infection. This review summarizes the role of NF-κB in COVID-19 and describes its potential immunotherapeutic target in treatment of SARS-CoV-2 infection. However, indisputably more studies involving patients with a severe course of COVID-19 are sorely needed. [ABSTRACT FROM AUTHOR]

COVID-19 together with variants have caused an unprecedented amount of mental and economic turmoil with ever increasing fatality and no proven therapies in sight. The healthcare industry is racing to find a cure with multitude of clinical trials underway to access the efficacy of repurposed antivirals, however the much needed insights into the dynamics of pathogenesis of SARS-CoV-2 and corresponding pharmacology of antivirals are lacking. This paper introduces systematic pathological model learning of COVID-19 dynamics followed by derivative free optimization based multi objective drug rescheduling. The pathological model learnt from clinical data of severe COVID-19 patients treated with remdesivir could additionally predict immune T cells response and resulted in a dramatic reduction in remdesivir dose and schedule leading to lower toxicities, however maintaining a high virological efficacy. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS‐CoV‐2 lifecycle and COVID‐19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID‐19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data. [ABSTRACT FROM AUTHOR]

Background: With the Coronavirus becoming a new reality of our world, global efforts continue to seek answers to many questions regarding the spread, variants, vaccinations, and medications. Particularly, with the emergence of several strains (e.g., Delta, Omicron), vaccines will need further development to offer complete protection against the new variants. It is critical to identify antiviral treatments while the development of vaccines continues. In this regard, the repurposing of already FDA-approved drugs remains a major effort. In this paper, we investigate the hypothesis that a combination of FDA-approved drugs may be considered as a candidate for COVID-19 treatment if (1) there exists an evidence in the COVID-19 biomedical literature that suggests such a combination, and (2) there is match in the clinical trials space that validates this drug combination. Methods: We present a computational framework that is designed for detecting drug combinations, using the following components (a) a Text-mining module: to extract drug names from the abstract section of the biomedical publications and the intervention/treatment sections of clinical trial records. (b) a network model constructed from the drug names and their associations, (c) a clique similarity algorithm to identify candidate drug treatments. Result and Conclusions: Our framework has identified treatments in the form of two, three, or four drug combinations (e.g., hydroxychloroquine, doxycycline, and azithromycin). The identifications of the various treatment candidates provided sufficient evidence that supports the trustworthiness of our hypothesis. [ABSTRACT FROM AUTHOR]

This paper is a summary of research that looks at the potential of fullerene-like (MO)12 nanoclusters (NCs) in drug-carrying systems using density functional theory. Favipiravir/Zn12O12 (− 34.80 kcal/mol), Favipiravir/Mg12O12 (− 34.98 kcal/mol), and Favipiravir/Be12O12 (− 30.22 kcal/mol) were rated in order of drug adsorption degrees. As a result, Favipiravir attachment to (MgO)12 and (ZnO)12 might be simple, increasing Favipiravir loading efficiency. In addition, the quantum theory of atoms in molecules (QTAIM) assessment was utilized to look at the interactions between molecules. The FMO, ESP, NBO, and Eads reactivity patterns were shown to be in excellent agreement with the QTAIM data. The electrostatic properties of the system with the biggest positive charge on the M atom and the largest Eads were shown to be the best. This system was shown to be the best attraction site for nucleophilic agents. The findings show that (MgO)12 and (ZnO)12 have great carrier potential and may be used in medication delivery. [ABSTRACT FROM AUTHOR]

Based on an in-depth survey of the literature, the purpose of the paper is to explore smart wearable Internet of Medical Things technologies, artificial intelligence-based diagnostic algorithms, and real-time healthcare monitoring systems in COVID-19 detection and treatment. In this research, previous findings were cumulated showing that big data analytics can optimize healthcare services in Internet of Medical Things, and we contribute to the literature by indicating that data connectivity and sharing are pivotal in healthcare services. Throughout January 2022, a quantitative literature review of the Web of Science, Scopus, and ProQuest databases was performed, with search terms including “COVID-19” + “smart wearable Internet of Medical Things technologies,” “artificial intelligence-based diagnostic algorithms,” and “real-time healthcare monitoring systems.” As research published between 2020 and 2022 was inspected, only 127 articles satisfied the eligibility criteria. By taking out controversial or ambiguous findings (insufficient/irrelevant data), outcomes unsubstantiated by replication, too general material, or studies with nearly identical titles, we selected 31 mainly empirical sources. Data visualization tools: Dimensions (bibliometric mapping) and VOSviewer (layout algorithms). Reporting quality assessment tool: PRISMA. Methodological quality assessment tools include: AMSTAR, Dedoose, Distiller SR, and SRDR. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis was to investigate the association between the use of glucocorticoids and the mortality of covid-19 patients. Trials were identified through a comprehensive systematic search of four medical databases including PubMed, Cochrane Library, Web of Science, and Embase. We also searched for relevant papers using the Google search engine and major Preprint platforms including Medrix, bioRxiv, and SSRN. A meta-analysis was performed on the pooled results of these studies. Fourteen studies were enrolled. Five studies were Chinese, and nine were foreign. In the foreign studies, we found use of steroids was associated with a decrease in mortality (RR, 0.81; 95% CI 0.68-0.97; p = 0.02) whilst in the Chinese studies the use of steroids was associated with an increase in mortality (RR, 1.70; 95% CI 1.10-2.63; p = 0.02). The foreign studies included high-dose and medium-dose groups. The medium-dose glucocorticoid group (0.5 mg/kg/d ≤ Prednisone ≤ 1.0 mg/kg/d) showed an association with decreased mortality of covid-19 patients (RR 0.86; 95% CI 0.75-1.00; p = 0.05). We also found an association with decreasing mortality of covid-19 patients (RR 0.65; 95% CI 0.43-0.98; heterogeneity p = 0.04) in patients treated for ≤ five days. In summary, this meta-analysis demonstrated that the use of a medium dose of glucocorticoids for a short time is likely to decrease mortality, although this needs clinical confirmation. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has affected the world extraordinarily. This disease has a potential to cause a significantly severe course of disease leading to respiratory complications, multiple organ failure and possibly death. In the fight against this pandemic-causing disease, medical professionals around the world are searching for pharmacological agents that could treat and prevent disease progression and mortality. To speed the search of promising treatment options, already existing pharmacological agents are repurposed for the potential treatment of COVID-19 and tested in clinical trials. The aim of this literature review is to investigate the efficacy and safety of repurposed pharmacological agents for the treatment of COVID-19 at different pathophysiologic stages of the disease. For this literature review, online-databases PubMed and Google Scholar were utilised. Keywords "COVID-19", "SARS-CoV-2", "pathogenesis", "drug targets", "pharmacological treatment", "cytokine storm", "coagulopathy" and individual drug names were used. Scientific articles, including reviews, clinical trials, and observational cohorts, were collected and analysed. Furthermore, these articles were examined for references to find more clinical trials testing for the potential treatment of COVID-19. In total, 97 references were used to conduct this research paper.Results: The most beneficial pharmacological agent for the treatment of COVID-19 are corticosteroids, especially dexamethasone, for the treatment of mechanically ventilated COVID-19 patients. Other promising agents are remdesivir for the treatment of patients with COVID-19 pneumonia requiring minimal supplemental oxygen therapy, and IL-6 receptor antagonist monoclonal antibodies in severe COVID-19. Lopinavir/ritonavir, as well as chloroquine or hydroxychloroquine with or without azithromycin demonstrate the least efficacy in the treatment of COVID-19. The clinical benefits of the treatment of a COVID-19-specific coagulopathy with increased dosing of anticoagulation need further research and confirmation of randomised controlled trials.Conclusion: The search for pharmacological treatment of COVID-19 has elicited great controversy. Whereas drugs like chloroquine, hydroxychloroquine, and lopinavir/ritonavir have not shown proven benefit, the agents remdesivir and dexamethasone are recommended for clinical use for the treatment of COVID-19. Further randomised trials for other pharmacological treatment strategies are awaited. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management. [ABSTRACT FROM AUTHOR]

Acupuncture is an important part of Chinese medicine that has been widely used in the treatment of inflammatory diseases. During the coronavirus disease 2019 (COVID-19) epidemic, acupuncture has been used as a complementary treatment for COVID-19 in China. However, the underlying mechanism of acupuncture treatment of COVID-19 remains unclear. Based on bioinformatics/topology, this paper systematically revealed the multi-target mechanisms of acupuncture therapy for COVID-19 through text mining, bioinformatics, network topology, etc. Two active compounds produced after acupuncture and 180 protein targets were identified. A total of 522 Gene Ontology terms related to acupuncture for COVID-19 were identified, and 61 pathways were screened based on the Kyoto Encyclopedia of Genes and Genomes. Our findings suggested that acupuncture treatment of COVID-19 was associated with suppression of inflammatory stress, improving immunity and regulating nervous system function, including activation of neuroactive ligand–receptor interaction, calcium signaling pathway, cancer pathway, viral carcinogenesis, Staphylococcus aureus infection, etc. The study also found that acupuncture may have additional benefits for COVID-19 patients with cancer, cardiovascular disease and obesity. Our study revealed for the first time the multiple synergistic mechanisms of acupuncture on COVID-19. Acupuncture may play an active role in the treatment of COVID-19 and deserves further promotion and application. These results may help to solve this pressing problem currently facing the world. [ABSTRACT FROM AUTHOR]

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has spread rapidly throughout the globe. The spectrum of disease is broad but among hospitalized patients with COVID-19, respiratory failure from acute respiratory distress syndrome is the leading cause of mortality. There is an urgent need for an effective treatment. The current focus has been developing novel therapeutics, including antivirals, protease inhibitors, vaccines and targeting the overactive cytokine response with anti-cytokine therapy. The overproduction of early response proinflammatory cytokines results in what has been described as a "cytokine storm" is leading eventually to death when the cells fail to terminate the inflammatory response. Accumulating evidence shows that inflammatory cytokines induce selectin ligands that play a crucial role in the pathogenesis of inflammatory diseases by mediating leukocyte migration from the blood into the tissue. Thus, the selectins and selectin ligands represent a promising therapeutic target for the treatment of COVID-19. In this paper, potential pan-selectin inhibitors were identified employing a virtual screening using a docking procedure. For this purpose, the Asinex and ZINC databases of ligands, including approved drugs, biogenic compounds and glycomimetics, altogether 923,602 compounds, were screened against the P-, L- and E-selectin. At first, the experimentally confirmed inhibitors were docked into all three selectins' carbohydrate recognition domains to assess the suitability of the screening procedure. Finally, based on the evaluation of ligands binding, we propose 10 purchasable pan-selectin inhibitors to develop COVID-19 therapeutics. [ABSTRACT FROM AUTHOR]

The aim of this paper is to synthesize and analyze existing evidence on virtual care technologies, wearable health monitoring sensors, and Internet of Medical Things-based smart disease surveillance systems in the diagnosis and treat- ment of COVID-19 patients. Using and replicating data from Deloitte, Ericsson ConsumerLab, GlobalWebIndex, McKinsey, PwC, Sony, and Sykes, we performed analyses and made estimates regarding artificial intelligence-based diagnostic algo- rithms in Internet of Things-supported healthcare delivery. Artificial intelligenceenabled wearable medical devices, virtualized care systems, and wireless biomedical sensing devices are pivotal in COVID-19 screening, testing, and treatment. Digital epidemiological surveillance in monitoring, detection, and prevention of COVID-19 is optimized by use of medical artificial intelligence, clinical and diagnostic decision support systems, machine learning-based real-time data sensing and processing, and smart healthcare devices and applications. Descriptive statistics of compiled data from the completed surveys were calculated when appropriate. [ABSTRACT FROM AUTHOR]

Background/aim: The aim of this descriptive article is to share the experience in Ege University, Turkey with favipiravir in the treatment of severe SARS-CoV-2 pneumonia. Materials and methods: This retrospective descriptive study included patients diagnosed with COVID-19 who presented with or developed severe pneumonia. Results: Forty patients who completed a full course (at least 5 days) of favipiravir were included in the study. At baseline, 30 (75%) patients required treatment for respiratory distress. Thirty-three patients (82.5%) were discharged from the hospital with full recovery, 6 patients (15%) died and 1 case (2.5%) was still at the intensive care unit (ICU) when this paper was written. Conclusion: This study provides relevant information for the treatment of COVID-19, suggesting that favipiravir was associated with significant clinical and laboratory improvements in the majority of the patients, is a safe drug with no serious side effects and would merit further investigation. [ABSTRACT FROM AUTHOR]

Many meta‐analyses have been published about the efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID‐19). Most of them included observational studies, and few have assessed HCQ as a prophylaxis or evaluated its safety profile. We searched multiple databases and preprint servers for randomized controlled trials (RCTs) that assessed HCQ for the treatment or prevention of COVID‐19. We summarized the effect of HCQ on mortality, viral clearance, and other clinical outcomes. Out of 768 papers screened, 21 RCTs with a total of 14,138 patients were included. A total of 9 inpatient and 3 outpatient RCTs assessed mortality in 8596 patients with a pooled risk difference of 0.01 (95% confidence interval [CI] 0.00–0.03, I2 = 1%, p = 0.07). Six studies assessed viral clearance at 7 days with a pooled risk ratio (RR) of 1.11 (95% CI 0.86–1.42, I2 = 61%, p = 0.44) and 5 studies at 14 days with a pooled RR of 0.96 (95% CI 0.89–1.04, I2 = 0%, p = 0.34). Several trials showed no significant effect of HCQ on other clinical outcomes and. Five prevention RCTs with 5012 patients found no effect of HCQ on the risk of acquiring COVID‐19. Thirteen trials showed that HCQ was associated with increased risk of adverse events. We observed, with high level of certainty of evidence, that HCQ is not effective in reducing mortality in patients with COVID‐19. Lower certainty evidence also suggests that HCQ neither improves viral clearance and other clinical outcomes, nor prevents COVID‐19 infection in patients with high‐risk exposure. HCQ is associated with an increased rate of adverse events. [ABSTRACT FROM AUTHOR]

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs. [ABSTRACT FROM AUTHOR]

Children are infected with coronavirus disease 2019 (COVID-19) as often as adults, but with fewer symptoms. During the first wave of the COVID-19 pandemic, multisystem inflammatory syndrome (MIS) in children (MIS-C), with symptoms similar to Kawasaki syndrome, was described in young minors testing positive for COVID-19. The United States (US) Centers for Disease Control and Prevention (CDC) defined MIS-C as occurring in <21-year-olds, triggering hundreds of PubMed-listed papers. However, postpubertal adolescents are no longer children biologically; the term MIS-C is misleading. Furthermore, MIS also occurs in adults, termed MIS-A by the CDC. Acute and delayed inflammations can be triggered by COVID-19. The 18th birthday is an administrative not a biological age limit, whereas the body matures slowly during puberty. This blur in defining children leads to confusion regarding MIS-C/MIS-A. United States and European Union (EU) drug approval is handled separately for children, defined as <18-year-olds, ascribing non-existent physical characteristics up to the 18th birthday. This blur between the administrative and the physiological meanings for the term child is causing flawed demands for pediatric studies in all drugs and vaccines, including those against COVID-19. Effective treatment of all conditions, including COVID-19, should be based on actual physiological need. Now, the flawed definition for children in the development of drugs and vaccines and their approval is negatively impacting prevention and treatment of COVID-19 in minors. This review reveals the necessity for redefining pediatric age groups to rapidly establish recommendations for optimal prevention and treatment in minors. [ABSTRACT FROM AUTHOR]