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In this paper, we provide a simple ODEs model with a generic nonlinear incidence rate function and incorporate two treatments, blocking the virus binding and inhibiting the virus replication to investigate the impact of calibration on model predictions for the SARS-CoV-2 infection dynamics. We derive conditions of the infection eradication for the long-term dynamics using the basic reproduction number, and complement the characterization of the dynamics at short-time using the resilience and reactivity of the virus-free equilibrium are considered to inform on the average time of recovery and sensitivity to perturbations in the initial virus free stage. Then, we calibrate the treatment model to clinical datasets for viral load in mild and severe cases and immune cells in severe cases. Based on the analysis, the model calibrated to these different datasets predicts distinct scenarios: eradication with a non reactive virus-free equilibrium, eradication with a reactive virus-free equilibrium, and failure of infection eradication. Moreover, severe cases generate richer dynamics and different outcomes with the same treatment. Calibration to different datasets can lead to diverse model predictions, but combining long- and short-term dynamics indicators allows the categorization of model predictions and determination of infection severity. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 principally weakens the hosts' innate immune system by impairing the interferon function and production. Type I interferons (IFNs) especially IFN-β are best known for their antiviral activities. IFNs accompanied by the standard care protocols have opened up unique opportunities for treating the coronavirus disease 2019 (COVID-19). The databases including PubMed, SCOPUS, EMBASE, and Google Scholar were searched up to October 30, 2020. The primary and secondary outcomes were considered discharge and mortality, respectively. The abovementioned outcomes of standard care protocol were compared with the standard care plus IFN-β in the confirmed COVID-19 patients. Out of 356 records identified, 12 randomized clinical trial studies were selected for full-text screening. Finally, 5 papers were included in the systematic review and 3 papers in the meta-analysis. The average mortality rate was reported as 6.195% and 18.02% in intervention and control groups, respectively. Likewise, the median days of hospitalization were lower in the intervention group (9 days) than the control group (12.25 days). According to meta-analysis, IFN-β was found to increase the overall discharge rate (RR = 3.05; 95% CI: 1.09–5.01). Our findings revealed that early administration of IFN-β in combination with antiviral drugs is a promising therapeutic strategy against COVID-19. [ABSTRACT FROM AUTHOR]

Coronavirus Disease-19 (COVID-19) is a major concern for the entire world in the current era. Coronavirus is a very dangerous infectious virus that spreads rapidly from person to person. It spreads in exponential manner on a global scale. It affects the doctors, nurse and other COVID-19 warriors those who are actively involved for the treatment of COVID-19 infected (CI) patients. So, it is very much essential to focus on automation and artificial intelligence (AI) in different hospitals for the treatment of such infected patients and all should be very much careful to break the chain of spreading this novel virus. In this paper, a novel patient service robots (PSRs) assignment framework and a priority based (PB) method using fuzzy rule based (FRB) approach is proposed for the assignment of PSRs for CI patients in hospitals in order to provide safety to the COVID-19 warriors as well as to the CI infected patients. This novel approach is mainly focused on lowering the active involvement of COVID-19 warriors for the treatment of high asymptotic COVID-19 infected (HACI) patients for handling this tough situation. In this work, we have focused on HACI and low asymptotic COVID-19 infected (LACI) patients. Higher priority is given to HACI patients as compared to LACI patients to handle this critical situation in order to increase the survival probability of these patients. The proposed method deals with situations that practically arise during the assignment of PSRs for the treatment of such patients. The simulation of the work is carried out using MATLAB R2015b. [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]

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the world's health systems for more than two years. This disease causes a high mortality rate followed by cytokine storm–induced oxidative stress and acute respiratory distress syndrome (ARDS). Therefore, many drugs have been considered with emphasis on their anti-inflammatory and antioxidant effects in controlling the consequences of SARS-CoV-2 infection. Icariin is a major bioactive pharmaceutical compound derived from Epimedium plants, which is known due to its anti-inflammatory and antioxidant effects. Additionally, the protective effects of icariin have been studied in different pathologies through modulating intracellular pathways. In addition to the potential effect of this compound on inflammation and oxidative stress caused by SARS-CoV-2 infection, it appears to interfere with intracellular pathways involved in viral entry into the cell. Therefore, this paper aims to review the molecular mechanisms of anti-inflammatory and antioxidant properties of icariin, and hypothesizes its potential to inhibit SARS-CoV-2 entry into host cells through modulating the intracellular pathways. [ABSTRACT FROM AUTHOR]

Purpose: In the wake of SARS-CoV-2's global spread, human activities from health to social life to education have been affected. Favipiravir and Molnupiravir exhibited novel hexokinase inhibition and we discuss advantages of this property in their COVID-19 inhibition potential. Methods: This paper describes molecular docking data of human hexokinase II with Favipiravir, Cyan 20, Remdesivir, 2DG, and Molnupiravir along with hexokinase inhibition assays. Results: Favipiravir, an antiviral drug previously cleared for treating the flu and ebola, has shown some promise in early trials to treat COVID-19. We observed potent human hexokinase inhibiting potential of Favipiravir (50%) as against 4% and merely 0.3% hexokinase inhibition with Molnupiravir and 2 Deoxy d glucose at 0.1 mM concentration supported by molecular docking studies. Conclusion: Favipiravir could continue to be part of the COVID-19 treatment regimen due to its resistance to host esterases, hexokinase inhibition potential and proven safety through human trials. [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]

We have previously published several papers illustrating numerous immunomodulatory and anti-inflammatory potential benefits when we repurposed safe, generic non-steroidal anti-inflammatory drugs (NSAIDs)/nitazoxanide/azithromycin (Kelleni's protocol), to early manage our COVID-19 pediatric, adult, and pregnant patients. In this manuscript, we discuss some recently published meta-analysis and clinical studies supporting our practice and discuss a molecular study that might be interpreted as an academic proof that our protocol might also prevent SARS-CoV-2 replication. Moreover, after aspirin has been suggested to be independently associated with reduced risk of mechanical ventilation, ICU admission and in-hospital mortality of COVID-19, we claim that the molecular interpretation of the results that led to this suggestion was not scientifically accurate, and we provide our academic interpretation confirming that low-dose aspirin is least likely to improve COVID-19 mortality through anticoagulation as was suggested. Furthermore, we describe other potential benefits related to aspirin-triggered lipoxins and resolvins while illustrating how NSAIDs interfere with COX-1, COX-2, SARS-CoV-2/ SARS-CoV-2 ORF protein-dependent activation of caspases and their subsequent mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis and necroptosis which were associated with COVID-19 complications. Similarly, NSAIDs are known caspase inhibitors and thus they might independently inhibit other caspase-related COVID-19-associated downstream pathological signaling mechanisms. Finally, we postulated that CARD-14, a caspase recruitment domain-containing protein, polymorphisms might play a role in the development of severe and critical COVID-19 and confirmed our old call to early adopt NSAIDs, as an integral part of Kelleni's protocol, as of choice in its management aiming to end this pandemic. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, most metabolomics studies are either underpowered, measure only a restricted subset of metabolites, compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model. Objectives: Here we provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict the patient's infection severity (i.e., mild or severe) and potential outcome (i.e., discharged or deceased). Methods: High resolution untargeted UHPLC-MS/MS analysis was performed on patient serum using both positive and negative ionization modes. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model was created. Results: The predictors were selected for their relevant biological function and include deoxycytidine and ureidopropionate (indirectly reflecting viral load), kynurenine (reflecting host inflammatory response), and multiple short chain acylcarnitines (energy metabolism) among others. Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. A blind validation study on an additional 90 patients predicted outcome and severity at ROC AUC of 0.83 (CI 0.74–0.91) and 0.76 (CI 0.67–0.86). Conclusion: Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment. [ABSTRACT FROM AUTHOR]

The widespread prevalence and mortality of coronavirus diseases-2019 (COVID-19) lead many researchers to study the SARS-CoV-s2 infection to find a treatment for this disease. Discovering the mechanisms of action of COVID-19 and coping at the cellular level with this disease can have better effects. Including the target tissues of this disease are the lungs and the immune system. It is stated that COVID-19 easily infiltrates into alveoli through its receptors and then starts to proliferate. Subsequently, with the weakening of immune cells and increase inflammatory cytokines, it increases the rate of inflammation in the body. Strengthening the immune system and inhibiting COVID-19 receptors can play a preventive or even therapeutic role for this disease. Nigella sativa (N. sativa) is one of the herbal medicines to possess numerous pharmacological effects related to several organs of the body. Among the extraordinary properties of this plant is improving asthma and several lung diseases. The recent studies have shown that N. sativa at the cellular level can inhibit COVID-19 receptors. It was also stated that performing regular exercise training (especially moderate-intensity exercise training) can modulate the immune system and have an anti-inflammatory effect. Since the use of herbal supplements with exercise can have tremendous therapeutic effects at the cellular level, the hypothesis to use the Nigella sativa along with exercise training to prophylaxis and treatment COVID-19 will be highlighted in this paper. [ABSTRACT FROM AUTHOR]

The outbreak of severe acute respiratory syndrome coronavirus 2 is regarded as a highly contagious disease that has challenged the healthcare systems worldwide with confirmed cases approaching 12 million and more than 50,000 deaths. Considering the worldwide cases of novel coronavirus disease (COVID-19), it remains a pandemic and the vaccines and therapeutic agents have yet to be developed to stop the spread of this outbreak. Due to the unavailability of specific treatment for the COVID-19, it can be viewed that the risk of cluster infection will continue to be present within the intermittent and small-scale outbreaks. Though the COVID-19 has been identified as a communicable disease, the preventive measures and response policies in South Korea are effectively serving the purpose and gained the confidence to overcome the COVID-19 crisis. This paper includes the exploratory data analysis of COVID-19 cases in South Korea till July 8, 2020. South Korea has reported the lowest death rate with the majority of the deaths, associated with persons with underlying health conditions or elderly infected individuals. Currently the infected patients (total 989) remaining in South Korea are mild cases owing to its robust health care system and quarantine inspection procedures followed by the Ministry of Health and Welfare of South Korea to flatten the COVID-19 curve. Although the COVID-19 countermeasures taken by the South Korean government may not be conclusive or universal for all, but its exemplary approach to tackle COVID-19 can aid countries across the globe to strengthen their response system for the future outbreak of such an infectious disease. [ABSTRACT FROM AUTHOR]

Introduction: In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. Methods: COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website (www.covid19-druginteractions.org), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. Findings: Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. Conclusion: Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment. [ABSTRACT FROM AUTHOR]

At present, no cure is available for COVID-19 but vaccines, antiviral drugs, immunoglobulins, or the combination of immunoglobulins with antiviral drugs have been suggested and are in clinical trials. The purpose of this paper is to discuss the role of a pharmacokinetic and viral load analysis as a basis for adjusting immunoglobulin dosing to treat COVID-19. We reviewed the pre-clinical and clinical literature that describes the impact of a high antigen load on pharmacokinetic data following antibody treatment. Representative examples are provided to illustrate the effect of high viral and tumor loads on antibody clearance. We then highlight the implications of these factors for facilitating the development and dosing of hyperimmune anti-SARS CoV2 immunoglobulin. Both nonclinical and clinical examples indicate that high antigen loads, whether they be viral, bacterial, or tumoral in origin, result in increased clearance and decreased area under the curve and half-life of antibodies. A dosing strategy that matches the antigen load can be achieved by giving initially high doses and adjusting the frequency of dosing intervals based on pharmacokinetic parameters. We suggest that study design and dose selection for immunoglobulin products for the treatment of COVID-19 require special considerations such as viral load, antibody-virus interaction, and dosing adjustment based on the pharmacokinetics of the antibody. [ABSTRACT FROM AUTHOR]

Danshen, a prominent herb in traditional Chinese medicine (TCM), is known for its potential to enhance physiological functions such as blood circulation, immune response, and resolve blood stasis. Despite the effectiveness of COVID-19 vaccination efforts, some individuals still face severe complications post-infection, including pulmonary fibrosis, myocarditis arrhythmias and stroke. This study employs a network pharmacology and molecular docking approach to investigate the potential mechanisms underlying the therapeutic effects of candidate components and targets from Danshen in the treatment of complications in COVID-19. Candidate components and targets from Danshen were extracted from the TCMSP Database, while COVID-19-related targets were obtained from Genecards. Venn diagram analysis identified common targets. A Protein–Protein interaction (PPI) network and gene enrichment analysis elucidated potential therapeutic mechanisms. Molecular docking evaluated interactions between core targets and candidate components, followed by molecular dynamics simulations to assess stability. We identified 59 potential candidate components and 123 targets in Danshen for COVID-19 treatment. PPI analysis revealed 12 core targets, and gene enrichment analysis highlighted modulated pathways. Molecular docking showed favorable interactions, with molecular dynamics simulations indicating high stability of key complexes. Receiver operating characteristic (ROC) curves validated the docking protocol. Our study unveils candidate compounds, core targets, and molecular mechanisms of Danshen in COVID-19 treatment. These findings provide a scientific foundation for further research and potential development of therapeutic drugs. [ABSTRACT FROM AUTHOR]

Previous studies have observed heterogeneous changes in domestic violence-related 911 calls, police incident reports, and arrests at the onset of the COVID-19 pandemic. In this study, we use a large-scale medical claims database with coverage of over 100 million patients to examine the impact on domestic violence victims' use of emergency department care for their injuries in the early weeks of the pandemic compared to the corresponding weeks in previous years. We find a 23–35% decrease in utilization of emergency medical services by domestic violence victims between March and June of 2020. Based on this finding, it is essential to use caution when using medical claims to measure domestic violence in future research covering this time period. Decreases in care utilization also have important implications for the detection, screening, and treatment of domestic violence injuries during future public health crises. [ABSTRACT FROM AUTHOR]

COVID-19 comorbid with noncommunicable chronic diseases (NCDs) complicates the diagnosis, treatment, and prognosis, and increases the mortality rate. The aim is to evaluate the effects of a restricted diet on clinical/laboratory inflammation and metabolic profile, reactive oxygen species (ROS), and body composition in patients with COVID-19 comorbid with NCDs. We conducted a 6-week open, pilot prospective controlled clinical trial. The study included 70 adult patients with COVID-19 comorbid with type 2 diabetes (T2D), hypertension, or nonalcoholic steatohepatitis (NASH). Interventions: a restricted diet including calorie restriction, hot water drinking, walking, and sexual self-restraint. Primary endpoints: COVID-19 diagnosis by detecting SARS-CoV-2 genome by RT-PCR; weight loss in Main group; body temperature; C-reactive protein. Secondary endpoints: the number of white blood cells; erythrocyte sedimentation rate; adverse effects during treatment; fasting blood glucose, glycosylated hemoglobin A1c (HbA1c), systolic/diastolic blood pressure (BP); blood lipids; ALT/AST, chest CT-scan. In Main group, patients with overweight lost weight from baseline (− 12.4%; P < 0.0001); 2.9% in Main group and 7.2% in Controls were positive for COVID-19 (RR: 0.41, CI: 0.04–4.31; P = 0.22) on the 14th day of treatment. Body temperature and C-reactive protein decreased significantly in Main group compared to Controls on day 14th of treatment (P < 0.025). Systolic/diastolic BP normalized (P < 0.025), glucose/lipids metabolism (P < 0.025); ALT/AST normalized (P < 0.025), platelets increased from baseline (P < 0.025), chest CT (P < 0.025) in Main group at 14 day of treatment. The previous antidiabetic, antihypertensive, anti-inflammatory, hepatoprotective, and other symptomatic medications were adequately decreased to completely stop during the weight loss treatment. Thus, the fast weight loss treatment may be beneficial for the COVID-19 patients with comorbid T2D, hypertension, and NASH over traditional medical treatment because, it improved clinical and laboratory/instrumental data on inflammation; glucose/lipid metabolism, systolic/diastolic BPs, and NASH biochemical outcomes, reactive oxygen species; and allowed patients to stop taking medications. Trial Registration: ClinicalTrials.gov NCT05635539 (02/12/2022): https://clinicaltrials.gov/ct2/show/NCT05635539?term=NCT05635539&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has reinforced the importance of rapid and wide dissemination of high-quality information. Indeed, I CNS Drugs i has published and is currently processing papers relevant to the COVID-19 pandemic, including Zheng et al. I Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination i (https://link.springer.com/article/10.1007/s40263-020-00756-y). [Extracted from the article]

Background: The COVID-19 pandemic produced system-level changes within the criminal legal system and community-based substance use disorder (SUD) treatment system with impacts on recovery efforts. This study examines rural and urban clinicians' perspectives of COVID-19 on SUD treatment delivery for people on community supervision. Methods: Virtual qualitative interviews were conducted between April and October 2020 with 25 community supervision clinicians employed by Kentucky's Department of Corrections (DOC), who conduct assessments and facilitate community-based treatment linkages for individuals on probation or parole. Transcripts were analyzed in NVivo using directed content analysis methods. Results: Clinicians were predominantly white (92%) and female (88%) with an average of over 9 years working in the SUD treatment field and 4.6 years in their current job. Four COVID-19 themes were identified by both rural and urban clinicians including: (1) telehealth increases the modes of communication, but (2) also creates paperwork and technological challenges, (3) telehealth requires more effort for inter/intra-agency collaboration, and (4) it limits client information (e.g., no urine drug screens). Two additional rural-specific themes emerged related to COVID-19: (5) increasing telehealth options removes SUD treatment transportation barriers and (6) requires flexibility with programmatic requirements for rural clients. Conclusions: Findings indicate the need for community-based SUD treatment providers approved or contracted by DOC to support and train clients to access technology and improve information-sharing with community supervision officers. A positive lesson learned from COVID-19 transitions was a reduction in costly travel for rural clients, allowing for greater engagement and treatment adherence. Telehealth should continue to be included within the SUD continuum of care, especially to promote equitable services for individuals from rural areas. [ABSTRACT FROM AUTHOR]

Objective: Treatment for COVID-19 is still urgent need for the critically ill and severe cases. UC-MSC administration has a therapeutic benefit for severe COVID-19 patients even in the recovery period. In this paper, we aimed to present our clinical experience with UC-MSC treatment in severe and critical severe COVID-19 patients. Methods: In this study we evaluated the clinical outcome of severe/critically severe 210 COVID-19 patients treated with UC-MSCs, 1–2 × 106 per kilogram to 210 patients from 15/10/2020 until 25/04/2021. Results: Out of 99 critically severe intubated patients we have observed good clinical progress/discharged from ICU in 52 (52.5%) patients. Where as 86 (77.5%) of 111 severe unintubated patients discharged from ICU. Intubated 47 (47.5%) patients and unintubated 25 (22.5%) patients pass away. Significantly higher survival was observed in patients who underwent UC-MSCs before intubation (OR = 1.475, 95% CI = 1.193–1.824 p < 0.001). It was observed that the SaO2 parameter tended to improve after UC-MSC therapy compared to all groups. But SaO2 parameter between intubated and unintubated groups was not statistically significant (p > 0.05), while in discharged cases SaO2 parameter was statistically significant (p = 0.01). Besides, there was a statistically significant relation with intubation status, age (OR = 3.868, 95% CI = 0.574–7.152 p = 0.02) and weigh (OR = 6.768, 95% CI = 3.423–10.112 p < 0.001) thus presented an elevated risk for COVID-19. The linear regression analysis confirmed that the high weight was associated with the risk of intubation in COVID-19 (p = 0.001). Conclusions: According to our results and from recent studies, UC-MSC treatment is safe with high potential to be used as an added therapeutic treatment for severe COVID-19 patients. Our experience showed that UC-MSC therapy may restore oxygenation and downregulate cytokine storm in patients hospitalized with severe COVID-19. We advice wider randomised studies to discover the detailed therapeutic pathophysiology of the MSCs on COVID-19 patients. MSCs transplantation improves the damaging effects of the cytokine storm through immunomodulation and improving tissue and organ repair. Severe patients who were unintubated were in the Phase I, while critical patients who were intubated were in the Phase II. The figure is created via biorender application, (BioRender.com). [ABSTRACT FROM AUTHOR]

Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Currently, there are no specific and efficient vaccines or drugs for COVID-19, particularly in severe cases. A wide range of variations in the clinical symptoms of different patients attributed to genomic differences. Therefore, personalized treatments seem to play a critical role in improving these symptoms and even similar conditions. Prompted by the uncertainties in the area of COVID-19 therapies, we reviewed the published papers and concepts to gather and provide useful information to clinicians and researchers interested in personalized medicine and cell-based therapy. One novel aspect of this study focuses on the potential application of personalized medicine in treating severe cases of COVID-19. However, it is theoretical, as any real-world examples of the use of genuinely personalized medicine have not existed yet. Nevertheless, we know that stem cells, especially MSCs, have immune-modulatory effects and can be stored for future personalized medicine applications. This theory has been conjugated with some evidence that we review in the present study. Besides, we discuss the importance of personalized medicine and its possible aspects in COVID-19 treatment, then review the cell-based therapy studies for COVID-19 with a particular focus on stem cell-based therapies as a primary personalized tool medicine. However, the idea of cell-based therapy has not been accepted by several scientific communities due to some concerns of lack of satisfactory clinical studies; still, the MSCs and their clinical outcomes have been revealed the safety and potency of this therapeutic approach in several diseases, especially in the immune-mediated inflammatory diseases and some incurable diseases. Promising outcomes have resulted in that clinical studies are going to continue. [ABSTRACT FROM AUTHOR]

The paper presents the results of a standard and complex treatment method using the peptide drug thymus thymalin in patients with COVID-19. One of the mechanisms of the immunomodulatory effect of thymalin is considered to be the ability of this peptide drug to influence the differentiation of human hematopoietic stem cells (HSCs). It was found that, as a result of standard treatment, patients in the control group showed a decrease in the concentration of the pro-inflammatory cytokine IL-6, C-reactive protein, D-dimer. The addition of thymalin to standard therapy accelerated the decline in both these indicators and the indicators of the T cell system. This has helped reduce the risk of blood clots in COVID-19 patients. The revealed properties of the thymus peptide preparation are the rationale for its inclusion in the complex treatment of coronavirus infection. Peptideswith potential biological activity against SARS-CoV-2 virus [29]. Note: Nitrogen atoms are shown in blue, oxygen atoms - in red, carbon atoms – in gray, hydrogen atoms – in white, and phosphorus atoms – in yellow [ABSTRACT FROM AUTHOR]

COVID-19 has been a major global health concern for the past three years, and currently we are still experiencing coronavirus patients in the following years. The virus, known as SARS-CoV-2, shares a similar genomic identity with previous viruses such as SARS-CoV and MERS-CoV. To combat the pandemic, modern drugs discovery techniques such as in silico experiments for docking and virtual screening have been employed to design new drugs against COVID-19. However, the release of new drugs for human use requires two safety assessment steps consisting of preclinical and clinical trials. To bypass these steps, scientists are exploring the potential of repurposing existing drugs for COVID-19 treatment. This approach involves evaluating antiviral activity of drugs previously used for treating respiratory diseases against other enveloped viruses such as HPV, HSV, and HIV. The aim of this study is to review repurposing of existing drugs, traditional medicines, and active secondary metabolites from plant-based natural products that target specific protein enzymes related to SARS-CoV-2. The review also analyzes the chemical structure and activity relationship between selected active molecules, particularly flavonol groups, as ligands and proteins or active sites of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Background: Effort to search for the optimal COVID-19 treatment has continuously been attempted. Thymosin alpha-1 have immunomodulatory properties which may be beneficial in case of viral infection. This study's goal is to determine whether thymosin alpha-1 is effective in treating people with moderate-to-severe COVID-19. Methods: We searched for literature in 4 database: Scopus, Europe PMC, Medline, ClinicalTrials.gov, and Cochrane Library until March 25th, 2023. If those articles have data on the efficacy of thymosin alpha-1 therapy on COVID-19, they would be included. Risk ratio (RR) and Mean Difference (MD) along with their 95% confidence intervals were used to pool the results of dichotomous and continuous variables, respectively. Results: Pooled data from 8 studies indicated that moderate to critical Covid-19 patients who were receiving thymosin alpha-1 therapy had significantly lower mortality from COVID-19 (RR 0.59; 95% CI 0.37–0.93, p = 0.02, I2 = 84%), but without any difference in the needs for mechanical ventilation (RR 0.83; 95% CI 0.48–1.44, p = 0.51, I2 = 74%) and hospital length of stay (MD 2.32; 95% CI – 0.93, 5.58, p = 0.16, I2 = 94%) compared to placebo. The benefits of thymosin alpha-1 on the mortality rate were significantly affected only by sample size (p = 0.0000) and sex (p = 0.0117). Conclusion: Our study suggests that treatment with thymosin alpha-1 may reduce mortality rate in moderate to critical COVID-19 patients. Randomized clinical trials (RCTs) are still required to verify the findings of our study. [ABSTRACT FROM AUTHOR]

Mucormycosis is a life-threatening opportunistic fungal infection seen in immunocompromised states. Rising incidence of mucormycosis among Coronavirus Disease-2019 infected individuals is an increasing concern in India. The disease which was endemic has blown out to become an epidemic. The purpose of this research is to study the epidemiology, management and outcome of Coronavirus Disease-2019 Associated Mucormycosis (CAM) cases. Additionally, the role of diabetes and steroids in the causation of CAM was determined. A hospital-based observational study was conducted at a tertiary care centre involving cases with rhino-orbital mucormycosis with recent history of COVID-19 infection. Out of 205,166(81%) cases had Diabetes Mellitus as a comorbid condition. Among them, 75(36.6%) cases were diagnosed with diabetes during COVID-19 treatment. 161/205(78.5%) cases received corticosteroids during COVID-19 treatment. Corticosteroids were notindicated in 43(26.7%) cases. 177/205(85.4%) cases were alive at the end of 12 weeks. 8 out of 10 deaths were seen in cases having diabetes. As the incidence of mucormycosis is increasing, better awareness among general population about the disease, early diagnosis and multidisciplinary approach is required to improve prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset. Methods: Nasopharyngeal swabs were collected at baseline (day 1, prior to first dose) and days 3, 5 (end-of-treatment visit), 10, 15, and 29. From these samples, change from baseline in SARS-CoV-2 RNA titers (determined by quantitative PCR), detection of infectious SARS-CoV-2 (by plaque assay), and SARS-CoV-2 viral error induction (determined by whole genome next-generation sequencing) were assessed as exploratory endpoints. Results: Molnupiravir was associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo (including 50% relative reduction at end-of-treatment) through day 10. Among participants with infectious virus detected at baseline (n = 96 molnupiravir, n = 97 placebo) and evaluable post-baseline samples, no molnupiravir-treated participant had infectious SARS-CoV-2 by day 3, whereas infectious virus was recovered from 21% of placebo-arm participants on day 3 and 2% at end-of-treatment. Consistent with molnupiravir's mechanism of action, sequence analysis demonstrated that molnupiravir was associated with an increased number of low-frequency transition errors randomly distributed across the SARS-CoV-2 RNA genome compared with placebo (median 143.5 molnupiravir, 15 placebo), while transversion errors were infrequent overall (median 2 in both arms). Outcomes were consistent regardless of baseline SARS-CoV-2 clade, presence of SARS-CoV-2-specific immune response, or viral load. Conclusions: A 5-day course of orally administered molnupiravir demonstrated a consistently greater virologic effect than placebo, including rapidly eliminating infectious SARS-CoV-2, in high-risk outpatients with mild-to-moderate COVID-19. Trial Registration : ClinicalTrials.gov, NCT04575597. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the outcomes of targeted COVID-19 treatments in immunocompromised patients with asymptomatic or mild COVID-19 during the period of expansion of the different Omicron subvariants in France. A retrospective monocentric observational study was performed. All immunocompromised patients aged 18 or more, with asymptomatic SARS-CoV-2 infection or mild COVID-19, and who had received a targeted treatment with sotrovimab, tixagevimab/cilgavimab, nirmatrelvir/ritonavir or remdesivir at the Bordeaux University Hospital from 1st January 2022 to 31st December 2022 were eligible. The primary outcomes of interest was defined as a composite of either (i) progression to moderate (WHO-Clinical Progression Scale at 4 or 5) or severe COVID-19 (WHO-CPS ≥ 6), or (ii) the occurrence of COVID-19-related death. The secondary outcomes of interest were the components of the primary outcome. Outcomes were collected until day 30 after targeted treatment administration or at discharge for patients still hospitalised in relation with COVID-19 at day 30. 223 immunocompromised patients received targeted treatment for asymptomatic SARS-CoV-2 infection or mild COVID-19: 114 received sotrovimab, 50 tixagevimab/cilgavimab, 49 nirmatrelvir/ritonavir, and 10 remdesivir. Among 223 treated patients, 10 (4.5%) progressed to moderate or severe disease: three patients (1.3%) progressed to moderate COVID-19 and 7 (3.1%) patients progressed to severe disease. Among them, 4 (1.8%) died of COVID-19. More than 95% of immunocompromised patients with asymptomatic SARS-CoV-2 infection or mild COVID-19 treated by targeted therapies during the Omicron subvariants era did not progress to moderate or severe disease. [ABSTRACT FROM AUTHOR]

COVID-19 is a serious virus that can have a lot of effects, one of which is a secondary bacterial infection that can be more life-threatening and even lethal than the initial viral infection. Hence a fast and sensitive HPLC/UV method was developed and validated for the first estimation of a binary mixture of molnupiravir (MOL) and ertapenem (ERT) as a co-administrated medicine for the management of COVID-19 in pharmaceutical dosage forms, and human plasma samples. The drug combination was separated within 5 min via RP-ODS column using isocratic elution with a mobile phase of 0.05 M phosphate buffer (pH 3.5): acetonitrile with a 76: 24% ratio v/v. The presented method provided a linear response ranging from 0.03 to 17.0 and 0.05–20 µg mL−1 with LOD values of 0.009 and 0.008 µg mL−1 for MOL and ERT respectively. The good separation and high sensitivity of the HPLC method provide the determination of the cited drugs in human plasma without matrix interference with a percent of recovery ranging from 94.97 ± 2.05 to 98.44 ± 1.92. Based on the results, this method could be utilized to monitor cited drugs in quality control and therapeutic laboratories. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has emerged as the most serious outbreak in recent years. Certain medications such as sofosbuvir (SOF), ledipasvir (LDV) and paracetamol (PAR) were proposed as a safer and recommended substance to control symptoms of COVID-19. Results: Using built-in spectrophotometer software, zero order and derivative spectra of the studied components, two extremely clear, quick, and sensitive spectrophotometric techniques for simultaneous determinations of SOF, LDV, as well as PAR have been developed. LDV was calculated using a zero order absorption spectrum at wavelength maxima of 333 nm. SOF and PAR were evaluated simultaneously using a first derivative spectrophotometer at 247.2 nm and 260.8 nm, respectively. The calibration graphs for SOF, LDV, and PAR are linear over ranges of concentrations of 8–60 µg/mL, 4–22 µg/mL, and 2–14 µg/mL, consequently. The suggested methodologyspecificity was investigated using laboratory manufactured (different ratios) mixtures, which were then effectively used to the analysis of Mpiviropack plus® and Panadol® pills. Valid limitations included accuracy, precision, and specificity. The methodologies were validated in accordance with some ICH standards. Conclusions: The methods proposed were simple, accurate, precise, and neither require any complex equipment nor specific software. [ABSTRACT FROM AUTHOR]

Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the meta-analysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = −5.74, 95% CI (−11.1, −0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases compared to control groups. However, more eligible studies are needed for analysis to increase the quality of evidence of ivermectin use in COVID-19. [ABSTRACT FROM AUTHOR]

Despite the existence of well-founded data around the relationship between reactive oxygen species (ROS) and glucose-6-phosphate dehydrogenase (G6PD), current research around G6PD-deficient patients with viral infections, and limitations as a result of their condition, are inadequate. Here, we analyze existing data around immunological risks, complications, and consequences of this disease, particularly in relation to COVID-19 infections and treatment. The relationship between G6PD deficiency and elevated ROS leading to increased viral load suggests that these patients may confer heightened infectivity. Additionally, worsened prognoses and more severe complications of infection may be realized in class I G6PD-deficient individuals. Though more research is demanded on the topic, preliminary studies suggest that antioxidative therapy which reduces ROS levels in these patients could prove beneficial in the treatment of viral infections in G6PD-deficient individuals. [ABSTRACT FROM AUTHOR]

Favipiravir (FAV) is an antiviral drug in tablets, which has been originally intended for the treatment of influenza and determined by methods based mostly on liquid chromatography. Recently, FAV has been also tried for the treatment of COVID-19 in many countries, Here we present for the first time in the literature a facile and sensitive stability-indicating UV-spectrophotometric method of determining FAV that is effective on a micromolar scale. This green method was developed in aqueous drug solutions. Acidic, basic, oxidative degradation at room temperature as well as thermal degradation studies at 60°C were performed and fully validated in accordance with ICH guidelines, with 230 and 323 nm detection wavelengths used in linearity studies. The developed method was linear at concentrations between 5.0 – 30.0 μg/mL with correlation coefficient > 0.99. FAV concentrations of 1.20 and 3.70 μg/mL were calculated as LOD and LOQ levels, respectively. Recovery results were found within satisfactory precision values of 99.6 – 100.88%. The developed method gives results statistically comparable with those obtained by the HPLC technique. Due to the elimination of FAV mainly in its intact form when applied at clinical doses, this method can easily be applied for clinical and routine analyses as well as in quality control laboratories. [ABSTRACT FROM AUTHOR]

Favipiravir and remdesivir have been included in the COVID-19 treatment guidelines panel of several countries. The main objective of the current work is to develop the first validated green spectrophotometric methods for the determination of favipiravir and remdesivir in spiked human plasma. The UV absorption spectra of favipiravir and remdesivir have shown some overlap, making simultaneous determination difficult. Due to the considerable overlap, two ratio spectra manipulating spectrophotometric methods, namely, ratio difference and the first derivative of ratio spectra, enabled the determination of favipiravir and remdesivir in their pure forms and spiked plasma. The ratio spectra of favipiravir and remdesivir were derived by dividing the spectra of each drug by the suitable spectrum of another drug as a divisor to get the ratio spectra. Favipiravir was determined by calculating the difference between 222 and 256 nm of the derived ratio spectra, while calculating the difference between 247 and 271 nm of the derived ratio spectra enabled the determination of remdesivir. Moreover, the ratio spectra of every drug were transformed to the first order derivative using ∆λ = 4 and a scaling factor of 100. The first-order derivative amplitude values at 228 and 251.20 nm enabled the determination of favipiravir and remdesivir, respectively. Regarding the pharmacokinetic profile of favipiravir (Cmax 4.43 µg/mL) and remdesivir (Cmax 3027 ng/mL), the proposed methods have been successfully applied to the spectrophotometric determination of favipiravir and remdesivir in plasma matrix. Additionally, the greenness of the described methods was evaluated using three metrics systems: the national environmental method index, the analytical eco-scale, and the analytical greenness metric. The results demonstrated that the described models were in accordance with the environmental characteristics. [ABSTRACT FROM AUTHOR]

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, guidance ("Japanese Guide") has been published by a working group of several academic societies and announced by the Ministry of Health, Labour, and Welfare. Steroids as a candidate treatment for COVID-19 were noted in the Japanese Guide. However, the prescription details for steroids, and whether the Japanese Guide changed its clinical practice, were unclear. This study aimed to examine the impact of the Japanese Guide on the trends in the prescription of steroids for COVID-19 inpatients in Japan. We selected our study population using Diagnostic Procedure Combination (DPC) data from hospitals participating in the Quality Indicator/Improvement Project (QIP). The inclusion criteria were patients discharged from hospital between January 2020 and December 2020, who had been diagnosed with COVID-19, and were aged 18 years or older. The epidemiological characteristics of cases and the proportion of steroid prescriptions were described on a weekly basis. The same analysis was performed for subgroups classified by disease severity. The study population comprised 8603 cases (410 severe cases, 2231 moderate II cases, and 5962 moderate I/mild cases). The maximum proportion of cases prescribed with dexamethasone increased remarkably from 2.5 to 35.2% in the study population before and after week 29 (July 2020), when dexamethasone was included in the guidance. These increases were 7.7% to 58.7% in severe cases, 5.0% to 57.2% in moderate II cases, and 1.1% to 19.2% in moderate I/mild cases. Although the proportion of cases prescribed prednisolone and methylprednisolone decreased in moderate II and moderate I/mild cases, it remained high in severe cases. We showed the trends of steroid prescriptions in COVID-19 inpatients. The results showed that guidance can influence drug treatment provided during an emerging infectious disease pandemic. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that people with schizophrenia are at high risk for severe COVID-19 and should be prioritized for vaccination. However, impaired decision-making capacities could negatively affect the uptake of COVID-19 vaccination in this population. Capacity to consent to COVID-19 vaccination was assessed in 80 outpatients with schizophrenia. Using the MacArthur Competence Assessment Tool for Treatment, 56.3% of the sample were classified as having diminished capacity to consent to the vaccination. Diminished capacity to consent to COVID-19 vaccination was associated with lower vaccination rates, poorer cognition and higher level of psychotic symptoms. Developing interventions for enhancing informed consent for vaccination is urgent within this population. [ABSTRACT FROM AUTHOR]

Coronavirus is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2. Coronavirus disease 2019 known as COVID-19 is the worst pandemic since World War II. The outbreak of COVID-19 had a significant repercussion on the health, economy, politics, and environment, making coronavirus-related issues more complicated and becoming one of the most challenging pandemics of the last century with deadly outcomes and a high rate of the reproduction number. There are thousands of different types — or variants — of COVID circulating across the world. Viruses mutate all the time; it emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis, and effective antiviral and protective therapeutics. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis, and treatment of COVID-19. This review presents an outline of the platforms developed using plasmonic nanoparticles in the detection, treatment, and prevention of SARS-CoV-2. We select the best strategies in each of these approaches. The properties of metallic plasmon NPs and their relevance in the development of novel point-of-care diagnosis approaches for COVID-19 are highlighted. Also, we discuss the current challenges and the future perspectives looking towards the clinical translation and the commercial aspects of nanotechnology and plasmonic NP-based diagnostic tools and therapy to fight COVID-19 pandemic. The article could be of significance for researchers dedicated to developing suitable plasmonic detection tools and therapy approaches for COVID-19 viruses and future pandemics. [ABSTRACT FROM AUTHOR]

Breakthrough infections have been reported in fully vaccinated persons. Furthermore, rebound symptoms have been reported following the new FDA granted emergency use to combat SARS-CoV-2. Glycyrrhizin (GR) and boswellic acids (BAs) combination has been shown to have highly successful actions against COVID-19 in our recent clinical trial. However, the study is limited by the small sample size, and therefore, the aim of this article is to comprehensively evaluate recent evidence on the efficacy of GR and BAs in preventing the development of COVID-19 in patients with mild and moderate infections and in preventing post-COVID-19 cognitive impairment, which is the most important symptom after recovery from Covid-19 disease. We have reviewed and discussed information published since the outbreak of the COVID-19 pandemic until July 2022 on preclinical (in vivo, in vivo and bioinformatics) and clinical studies related to the antiviral, anti-inflammatory and immunomodulatory activity of Gr and BAs. Sixteen studies were performed to determine the efficacy of GR against SARS-CoV-2. Ten studies were used primarily for in vitro and in vivo assays and six used molecular docking studies. However, the antiviral activity of BAs against SARS-CoV-2 was determined in only five studies using molecular modeling and bioinformatics. All these studies confirmed that GR n and BAs have strong antiviral activity and can be used as a therapeutic agent for COVID-19 and as a protective agent against SARS-CoV-2. They may act by inhibiting the main protease SARS-CoV-2 (Mpro) responsible for replication and blocking spike protein-mediated cell entry. Only seven rigorously designed clinical trials regarding the usefulness of GR, BAs or their combinations in the treatment of COVID-19 have been published as of July 2022. Although there is no clinical study regarding the treatment of cognitive impairment after COVID-19 that has been published so far, several preclinical and clinical studies have demonstrated the potential effect of GR and BAs in the prevention and treatment of cognitive impairment by inhibiting the activity of several molecules that activate inflammatory signaling pathway. In conclusion, the findings of our study documented the beneficial use of GR and BAs to treat SARS-CoV-2 and its variants and prevent post-COVID cognitive impairment. However, it warrants further studies with a larger randomized sample size to ensure that the studies have sufficient evidence of benefits against COVID-19 and post-COVID-19 symptoms. [ABSTRACT FROM AUTHOR]

Lianhuaqingwen (LH), one traditional Chinese medicine (TCM), has been used to treat the coronavirus disease 2019 (COVID-19), but its ecotoxicity with potential human health security has not been well investigated. To overcome such adverse effects and improve its medication efficacy, an intelligent multi-method integrated dietary scheme, screening, and performance evaluation approach was developed. Thirteen LH compounds were selected, and the main protease (Mpro) was used as the potential drug target. Resulted information showed that the more compounds of LH added, the higher medication efficacy obtained using multi-method integrated screening system, expert consultation method, and molecular dynamics simulation. Pharmacodynamic mechanism analysis showed that low total energy and polar surface area of LH active compound (i.e., β-sitosterol) will contribute to the best therapeutic effect on COVID-19 using quantitative structure-activity relationships (QSAR) and sensitivity models. Additionally, when mild COVID-19 patients take LH with the optimum dietary scheme (i.e., β-lactoglobulin, α-lactalbumin, vitamin A, vitamin B, vitamin C, carotene, and vitamin E), the medication efficacy were significantly improved (23.58%). Pharmacokinetics and toxicokinetics results showed that LH had certain human health risks and ecotoxicity. This study revealed the multi-compound interaction mechanism of LH treatment on COVID-19, and provided theoretical guidance for improving therapeutic effect, evaluating TCM safety, and preventing human health risk. [ABSTRACT FROM AUTHOR]

Anosmia and ageusia are the first and maybe the only symptom in patients affected with COVID-19 especially if the patient is paucisymptomatic. This aim of this study was to determine the demographic details of patients with anosmia, prevalence of anosmia and the time taken for it to resolve in patients who are positive for COVID-19 and took treatment in our hospital. Cross Sectional Study. Patients with real time polymerase chain reaction (RTPCR) positive nasopharyngeal and oropharyngeal swabs, who met the inclusion and exclusion criteria were included in the study. The study group was interviewed through telephonic calls and a questionnaire filled to see the development and regression of their symptoms. Of the study population of 1000, 742 patients had some sort of a smell disturbance. There was a positive correlation between the severity of the disease and history of smoking. The prevalence of smell disturbances among COVID-19 patients in our study was 74.2%. One important finding that we found out was that majority of the smokers had moderate disease. Most of the patients had complete recovery form smell disturbance in the due course of time. The mean time for resolution of smell disturbance was found to be 9.89 days. Anosmia and ageusia can represent the only symptomatology present in patients with COVID-19 and they are completely reversible and hence they can be used as early predictors of infection. Level of Evidence: Level 2. [ABSTRACT FROM AUTHOR]

The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the "Omicron variant." Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral pills against SARS-CoV-2, i.e., molnupiravir and paxlovid, that inhibit SARS-CoV-2 viral replication by acting on the RNA polymerase of SARS-CoV. In pre-registration clinical trials, molnupiravir and paxlovid have shown excellent clinical efficacy results, but what impact will these new oral antiviral agents have against pandemic COVID-19? In what specific clinical situations are they preferred over other antivirals such as remdesivir? In this brief review, we explore these important aspects. [ABSTRACT FROM AUTHOR]

The efforts of the scientific world directed to identifying new antiviral drugs and therapies effective against SARS-CoV-2 continue. New oral antivirals against SARS-CoV-2 such as paxlovid have recently authorized. Evidence shows that these antivirals have good efficacy in reducing the risk of hospitalization in COVID-19 positive patients. Remdesivir is an authorized antiviral for the treatment of SARS-CoV-2 infection. To date, there are still few data in the literature on the safety profile and the risk of generating antiviral-resistant SARS-CoV-2 drug variants. In this manuscript we describe the evidence in the literature on the monotherapy use of paxlovid and monotherapy use of remdesivir, and the scientific hypothesis of using nirmatrelvir and remdesivir in association with the aim of increasing treatment efficacy, reducing the risk of adverse reactions and generating antiviral drug-resistant variants. [ABSTRACT FROM AUTHOR]

The 2019 outbreak of corona virus disease began from Wuhan (China), transforming into a leading pandemic, posing an immense threat to the global population. The WHO coined the term nCOVID-19 for the disease on 11th February, 2020 and the International Committee of Taxonomy of Viruses named it SARS-CoV-2, on account of its similarity with SARS-CoV-1 of 2003. The infection is associated with fever, cough, pneumonia, lung damage, and ARDS along with clinical implications of lung opacities. Brief understanding of the entry target of virus, i.e., ACE2 receptors has enabled numerous treatment options as discussed in this review. The manuscript provides a holistic picture of treatment options in COVID-19, such as non-specific anti-viral drugs, immunosuppressive agents, anti-inflammatory candidates, anti-HCV, nucleotide inhibitors, antibodies and anti-parasitic, RNA-dependent RNA polymerase inhibitors, anti-retroviral, vitamins and hormones, JAK inhibitors, and blood plasma therapy. The text targets to enlist the investigations conducted on all the above categories of drugs, with respect to the COVID-19 pandemic, to accelerate their significance in hindering the disease progression. The data collected primarily targets recently published articles and most recent records of clinical trials, focusing on the last 10-year database. The current review provides a comprehensive view on the critical need of finding a suitable treatment for the currently prevalent COVID-19 disease, and an opportunity for the researchers to investigate the varying possibilities to find and optimized treatment approach to mitigate and ameliorate the chaos created by the pandemic worldwide. [ABSTRACT FROM AUTHOR]

Background: Recent Coronavirus Disease-19 (COVID-19) pandemic shows that health system, particularly hospital care, takes the highest toll on COVID-19. As hospital gets to manage the surge of COVID-19 cases, it is important to standardize treatment standard and package for COVID-19. Until recently, in Indonesia, COVID-19 curative package in hospital is paid using a retrospective payment system (claims system) using a per-diem rate. Quantifying standard cost using an established retrospective claims dataset is important as a basis for standard formulation for COVID-19 package treatment, should COVID-19 be accommodated into the benefit package for Universal Health Coverage (UHC) under the National Health Insurance. Methods: We estimated a standard cost for COVID-19 treatment using provider's perspective. The analysis was conducted retrospectively using established national COVID-19 claims dataset during January 2020 until 2021. Utilizing individual-or-patient level analysis, claims profile were broken down per-patient, yielding descriptive clinical and care-related profile. Estimate of price and charge were measured in average. Moreover, indicators were regressed to the total charged price (in logarithmic scale) so as to find the predictors of cost. Results: Based on the analysis of 102,065 total claims data received by MOH in 2020-2021, there is an average claim payment for COVID-19 in the amount of IDR 74,52 million (USD$ 5175). Significant difference exists in hospital tariffs or price to the existing claims data, indicating profit for hospital within its role in managing COVID-19 cases. Claim amount predictors were found to be associated with change of claim amount, including high level of severity, hospital class, intensive care room occupancy and ventilator usage, as well as mortality. Conclusion: As COVID-19 pandemic shifts towards an endemic, countries including Indonesia need to reflect on the existing payment system and move towards a more sustainable payment mechanism for COVID-19. The COVID-19 payment system needs to be integrated into the existing national health insurance allowing bundled payment to become more sustainable, which can be achieved by comprehensively formulating the bundled payment package for COVID-19. [ABSTRACT FROM AUTHOR]

References 1 Cag Y, Icten S, Isik-Goren B, Baysal NB, Bektas B, Selvi E et al (2020) A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort. Thus far, the PCR test is the only available method to establish a definitive diagnosis of COVID-19. A novel approach to managing COVID-19 patients: results of lopinavir plus doxycycline cohort - authors' reply. [Extracted from the article]

Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using publicly available metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 patients with cancer had poorer outcomes due to immunosuppression during cancer care, poor general condition, and other comorbidities. The study was conducted to present the real-world analysis of the effect of treatment interruptions on the outcomes of patients treated with radiation therapy during the first wave of the COVID-19 pandemic in a tertiary care institute in India. Materials and methods: The study is a retrospective observational cohort study on cancer patients undergoing radiation therapy from March 2020 to January 2021. The study's primary outcome was to analyze the effect of treatment interruptions on the outcomes of patients treated with radiation therapy during the first wave of COVID-19 pandemic. Results: Between March 2020 to January 2021, 218 eligible patients undergoing radiation therapy were found for the study. Among the 218 patients, 25 patients (11.47%) were found positive for COVID-19, while 193 patients (88.53%) were negative for COVID-19. Among COVID-19-positive patients, ten patients had < 3 weeks of treatment interruption, while 15 patients had > 3 weeks of treatment interruptions. After recovering from COVID-19, treatment was resumed and completed for 15 (60.00%) of the COVID-19-positive patients. In comparison, 13 patients (52.00%) were lost to follow-up. Three of the COVID-19-positive patients died. The disease was clinically controlled in 12 (48.00%) of the COVID-19-positive patients, and the patients reported locoregional disease progression in 10 (40.00%). Among the 193 COVID-19-negative patients, 32 patients (16.58%) had treatment interruption. Twelve patients (37.50%) had treatment interruptions for less than 1 week. There was a significant difference in the delay of radiation treatment delivery by 2 weeks (11 fractions) in COVID-19-positive patients compared to only two fractions delay in COVID-19-negative patients. Conclusion: COVID-19 impacted the treatment outcomes in both COVID-19-positive and COVID-19-negative cohorts of patients. There was a longer duration of treatment interruptions in the COVID-19-positive patients, leading to fewer patients completing the radiation treatment and thereby increased locoregional disease progression. There was a significant difference in the delay in treatment between the two groups. [ABSTRACT FROM AUTHOR]

First discovered in Wuhan, China, SARS-CoV-2 is a highly pathogenic novel coronavirus, which rapidly spread globally and became a pandemic with no vaccine and limited distinctive clinical drugs available till March 13th, 2020. Ribonucleic Acid interference (RNAi) technology, a gene-silencing technology that targets mRNA, can cause damage to RNA viruses effectively. Here, we report a new efficient small interfering RNA (siRNA) design method named Simple Multiple Rules Intelligent Method (SMRI) to propose a new solution of the treatment of COVID-19. To be specific, this study proposes a new model named Base Preference and Thermodynamic Characteristic model (BPTC model) indicating the siRNA silencing efficiency and a new index named siRNA Extended Rules index (SER index) based on the BPTC model to screen high-efficiency siRNAs and filter out the siRNAs that are difficult to take effect or synthesize as a part of the SMRI method, which is more robust and efficient than the traditional statistical indicators under the same circumstances. Besides, to silence the spike protein of SARS-CoV-2 to invade cells, this study further puts forward the SMRI method to search candidate high-efficiency siRNAs on SARS-CoV-2's S gene. This study is one of the early studies applying RNAi therapy to the COVID-19 treatment. According to the analysis, the average value of predicted interference efficiency of the candidate siRNAs designed by the SMRI method is comparable to that of the mainstream siRNA design algorithms. Moreover, the SMRI method ensures that the designed siRNAs have more than three base mismatches with human genes, thus avoiding silencing normal human genes. This is not considered by other mainstream methods, thereby the five candidate high-efficiency siRNAs which are easy to take effect or synthesize and much safer for human body are obtained by our SMRI method, which provide a new safer, small dosage and long efficacy solution for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Molecular diagnostics using RT-PCR has now emerged as the new diagnostic method for clinicians with the dawn of SARS-CoV-2. In India, the popularity and awareness of RT-PCR and particularly the increased availability of testing machines across hospitals has now opened up possibilities of diagnostic tests with RT-PCR. In view of the cytokine storm which is the significant reason for morbidity and mortality of COVID-19 patients, we proposed to test the usefulness of a multiplex RT-PCR test kit that simultaneously measured inflammatory markers namely, IL-6, TNF– α and IL-10 (IFM) all in one tube. The study included a group of patients who were equally allotted to two treatment arms one of which received standard of care along with a food supplement capsule as a natural anti-inflammatory (RECOVEREEZ FORTE™), and the other group received standard of care that included oral Prednisolone tablets in tapered dosage. RECOVEREEZ FORTE™ consists of potent biomolecules from cardamom extract. A natural product with substantial anti-inflammatory action when consumed early at the onset of symptoms is hereby proven by comparing gene expression profile of inflammatory markers with routinely tested inflammatory parameters such as serum IL-6, CRP and LDH. In addition to predicting worse disease outcomes beforehand, RT-PCR assay tests provides an opportunity for identifying therapeutic window aiding in practicing effective treatment strategy for COVID-19. RT-PCR analysis of IFM together being used in a single multiplex kit is being first reported and such a test as a prognosticator for disease progression does seem promising and worthy of clinicians adopting novel testing modalities in clinical practice. Aim of the study: To study the anti-inflammatory response of RECOVEREEZ FORTE™ using RT-PCR based multiplex gene profiling of inflammatory markers in disease prognosis and show its predictability of worsening outcomes and its role in identifying therapeutic window for RECOVEREEZ FORTE™. To show the potentiality of RECOVEREEZ FORTE™ in reducing COVID-19 symptoms and SARS-CoV-2 RT-PCR Ct values of the treatment group. Materials and methods: This was a short study of a 10-day period where the end point was the negativity of COVID-19 on RT-PCR test or the decline in cycle threshold (Ct) values of the test performed on day 10 when compared to day 0. During the course of the study, patients were given standard treatment and an oral dose of 500 mg of RECOVEREEZ FORTE™ thrice daily, or standard of care and oral Prednisolone in tapered dosage (control group). All essential interventions were included in the standard of care as decided by the attending physician. The RT-PCR results of inflammatory markers were compared to routinely tested parameters such as IL-6, CRP and LDH. Time to clinical improvement was in terms of SARS-CoV-2 RT-PCR test negativity or recovery of COVID-19 symptoms. We enrolled 64 patients, of which 32 were allocated to RECOVEREEZ FORTE ™ group and 32 to the control group. Results: The RT-PCR analysis of elevated IFM on day 0 corresponded to above normal protein levels of routinely tested parameters such as serum IL-6, CRP and LDH on day 5. Similarly, elevated IFM on day 5 corresponded to above normal protein levels on day 10. Such an association was equally prevalent in both the control group and RECOVEREEZ FORTE™ group, stipulating that RECOVEREEZ FORTE™ may be used as an alternative to steroids. The obtained results indicate that the RT-PCR assessment predicts worse outcomes 5 days earlier. But, the RT-PCR analysis of elevated IFM on day 0 did not correspond to the above normal protein levels of other parameters on day 10. Hence, indicating that the IFM RT-PCR test cannot predict worse outcomes 10 days earlier. Also, RECOVEREEZ FORTE™ when consumed for a period of 10 days normalized LDH values, compared to the control group. Moreover, IFM RT-PCR test identified a 5-day therapeutic window for RECOVEREEZ FORTE™ against inflammation experienced by patients. In addition to the above findings, the authors also observed that majority of the patients belonging to the treatment group showed recovery from symptoms such as fever, cough, sore throat and breathlessness compared to control group by day 5. 12 (37.5%) out of 32 patients and 6 (18.75%) out of 32 patients belonging to the treatment group and control group, respectively, became SARS-CoV-2 negative by day 5, indicating a probable anti-viral action of RECOVEREEZ FORTE™ against SARS-CoV-2. Conclusion: The IFM RT-PCR test possess 5-day early prediction ability and lacks 10-day prediction ability. Treatment with RECOVEREEZ FORTE™ indicates good anti-inflammatory action which is equivalent to steroids. Intake of RECOVEREEZ FORTE ™ for a period of 5 days depicts persistent anti-inflammatory action, recovery of COVID-19 symptoms and a probable anti-viral action. Moreover, an effective normalization of LDH may be rendered by RECOVEREEZ FORTE™ when consumed for a period of 10 days. [ABSTRACT FROM AUTHOR]

Background: In the last few years, several studies confirmed the effectiveness of music therapy (MT) for the rehabilitative management of patients with neurological disorders.Aim: Here we discuss the feasibility and disadvantages of tele-neurological MT (tele-NMT) compared to the traditional MT programmes.Methods: We selected all the articles registered in the Web of Knowledge, PubMed, Google Scholar and ScienceDirect from March 2020 to November 2021 concerning tele-NMT during the COVID-19 outbreak, collecting same examples and experiences.Results: With the advent of the COVID-19, several music-based interventions (MBIs) have been adapted from "in person" to a "remote and virtual" mode (through the telemedicine).Discussion: Tele-NMT could represent a promising option to provide constant care and support to people with neurological diseases during the pandemic. [ABSTRACT FROM AUTHOR]