Treatment Of COVID-19 Research Articles

Advanced biomaterials for regenerative medicine and their possible therapeutic significance in treating COVID-19: a critical overview.

The potential of biomaterials in medical sciences has attracted much interest, especially in promoting tissue regeneration and controlling immune responses. As COVID-19 pandemic broke out, there was an increased interest in understanding more about how biomaterials could be employed to fight this dreaded disease, especially in the context of regenerative medicine. Out of the numerous regenerative medicine possibilities, stem cells and scaffolding (grafting) technology are two major areas in modern medicines and surgery. Mesenchymal stem cells are useful in tissue repair, tailored therapy and treating COVID-19. Using biomaterials in COVID-19 treatment is intricate that needs multi- and cross-disciplinary research. Cell-based therapy and organ transplant pose immunological rejection challenge. Immunomodulation enhanced, tumorigenicity decreased, inflammation addressed and tissue damage restricted bioengineered stem cells need clinical insights and validation. Advanced stem cell based therapies should ideally be effective, safe and scalable. Cost and scalability shall dictate the dawn of technoeconomically feasible regenerative medicine. A globally standard and uniform approval process could accelerate translational regenerative medicine. Researchers, patient advocacy organisations, the regulators and the biopharmaceutical stakeholders need to join hands for easy navigation of regulatory measures and expeditious market entry of regenerative medicine. This article summarises advances in biomaterials for regenerative medicine, and their possible therapeutic benefits in managing infectious diseases like COVID-19. It highlights the significant recent developments in biomaterial design, scaffold construction, and stem cell-based therapies to treat tissue damage and COVID-19 linked immunological disregulation. It also highlights the potential contribution of biomaterials towards creating novel treatment strategies to manage COVID-19.

Peptide-Based Inhibitors of Protein-Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2).

Protein-protein interactions (PPIs) are fundamental to many critical biological processes and are crucial in mediating essential cellular functions across diverse organisms, including bacteria, parasites, and viruses. A notable example is the interaction between the SARS-CoV-2 spike (S) protein and the human angiotensin-converting enzyme 2 (hACE2), which initiates a series of events leading to viral replication. Interrupting this interaction offers a promising strategy for blocking or significantly reducing infection, highlighting its potential as a target for anti-SARS-CoV-2 therapies. This review focuses on the hACE2 and SARS-CoV-2 spike protein interaction, exemplifying the latest advancements in peptide-based strategies for developing PPI inhibitors. We discuss various approaches for creating peptide-based inhibitors that target this critical interaction, aiming to provide potential treatments for COVID-19.

Immunomodulatory effect of IFN-γ licensed adipose-mesenchymal stromal cells in an in vitro model of inflammation generated by SARS-CoV-2 antigens

In recent years, clinical studies have shown positive results of the application of Mesenchymal Stromal Cells (MSCs) in severe cases of COVID-19. However, the mechanisms of immunomodulation of IFN-γ licensed MSCs in SARS-CoV-2 infection are only partially understood. In this study, we first tested the effect of IFN-γ licensing in the MSC immunomodulatory profile. Then, we established an in vitro model of inflammation by exposing Calu-3 lung cells to SARS-CoV-2 nucleocapsid and spike (NS) antigens, and determined the toxicity of SARS-CoV-2 NS antigen and/or IFN-γ stimulation to Calu-3. The conditioned medium (iCM) generated by Calu-3 cells exposed to IFN-γ and SARS-CoV-2 NS antigens was used to stimulate T-cells, which were then co-cultured with IFN-γ-licensed MSCs. The exposure to IFN-γ and SARS-CoV-2 NS antigens compromised the viability of Calu-3 cells and induced the expression of the inflammatory mediators ICAM-1, CXCL-10, and IFN-β by these cells. Importantly, despite initially stimulating T-cell activation, IFN-γ-licensed MSCs dramatically reduced IL-6 and IL-10 levels secreted by T-cells exposed to NS antigens and iCM. Moreover, IFN-γ-licensed MSCs were able to significantly inhibit T-cell apoptosis induced by SARS-CoV-2 NS antigens. Taken together, our data show that, in addition to reducing the level of critical cytokines in COVID-19, IFN-γ-licensed MSCs protect T-cells from SARS-CoV-2 antigen-induced apoptosis. Such observations suggest that MSCs may contribute to COVID-19 management by preventing the lymphopenia and immunodeficiency observed in critical cases of the disease.

Statins for the treatment of COVID-19 patients: an updated meta-analysis of randomized controlled trials

BackgroundStatin is a low-cost and easily accessible therapeutic option for COVID-19 patients. Previous observational studies and meta-analyses suggest using statins for COVID-19 patients.MethodsDatabases including Medline, Scopus, Embase, Cochrane Library, and clinicaltrials.gov were systematically searched.ResultsAfter screening 754 records, 9 trials were included. Overall, the study demonstrated a non-significant reduction in all-cause mortality (p = 0.14, RR 0.90, 95% CI 0.79–1.03), no significant difference in the need for mechanical ventilation (p = 0.62, RR 0.95, 95% CI 0.77–1.17), and a non-significant reduction in length of hospitalization (p = 0.71, MD − 0.17 (95% CI − 1.09, 0.76)). The certainty of evidence varied across outcomes, with most demonstrating reasonable certainty.ConclusionOur study did not support clinical efficacy of statins for the treatment of COVID-19.

Safety and Efficacy of Chyawanprash as a Prophylaxis Treatment for COVID-19: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Amidst the multifaceted challenges posed by COVID-19, interest in complementary and alternative medicine (CAM) has risen. Chyawanprash (CP), an Ayurvedic formulation, is recognized for its multifunctional properties. This systematic review aims to evaluate its safety and effectiveness as a COVID-19 prophylactic.A literature search was conducted for articles published within the past three years from databases such as Cochrane Library, PubMed, and Google Scholar. A total of 1008 articles were identified, and 34 were included for full-text screening, resulting in five randomized controlled trials (RCTs) meeting the eligibility criteria. Meta-analysis was performed using a random effects model, with results represented in odds ratio (95% confidence intervals (CIs)), and publication bias presented through funnel plots.The five clinical trials conducted in India analyzed 153,343 participants. In the meta-analysis, the odds ratios for COVID-19-positive patients, COVID-19-positive in symptomatic patients, healthcare resource utilization (HCRU), and adverse events were 0.45 (95% CI 0.06-3.08, p = 0.41), 0.37 (95% CI 0.01-12.86, p = 0.58), 0.95 (95% CI 0.18-5.04, p = 0.95), and 0.94 (95% CI 0.63-1.40, p = 0.75) respectively. Notably, significant heterogeneity was observed among studies including both COVID-19-positive cases (I2= 80%, p = 0.007) and symptomatic COVID-19 cases (I2= 83%, p = 0.01), whereas non-significant zero heterogeneity was observed in HCRU (I2=0%, p = 0.74) and adverse events (I2= 0%, p = 1.00). The meta-analysis reveals a trendin the efficacy of CP as prophylaxis for COVID-19 treatments. However, owing to high heterogeneity and bias, further research is recommended.

Anti-Inflammatory and Neuroprotective Polyphenols Derived from the European Olive Tree, Olea europaea L., in Long COVID and Other Conditions Involving Cognitive Impairment

The European olive tree, Olea europaea L., and its polyphenols hold great therapeutic potential to treat neuroinflammation and cognitive impairment. This review examines the evidence for the anti-inflammatory and neuroprotective actions of olive polyphenols and their potential in the treatment of long COVID and neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Key findings suggest that olive polyphenols exhibit antioxidant, anti-inflammatory, neuroprotective, and antiviral properties, making them promising candidates for therapeutic intervention, especially when formulated in unique combinations. Recommendations for future research directions include elucidating molecular pathways through mechanistic studies, exploring the therapeutic implications of olive polyphenol supplementation, and conducting clinical trials to assess efficacy and safety. Investigating potential synergistic effects with other agents addressing different targets is suggested for further exploration. The evidence reviewed strengthens the translational value of olive polyphenols in conditions involving cognitive dysfunction and emphasizes the novelty of new formulations.

A seamless Phase I/II platform design with a time-to-event efficacy endpoint for potential COVID-19 therapies.

In the search for effective treatments for COVID-19, the initial emphasis has been on re-purposed treatments. To maximize the chances of finding successful treatments, novel treatments that have been developed for this disease in particular, are needed. In this article, we describe and evaluate the statistical design of the AGILE platform, an adaptive randomized seamless Phase I/II trial platform that seeks to quickly establish a safe range of doses and investigates treatments for potential efficacy. The bespoke Bayesian design (i) utilizes randomization during dose-finding, (ii) shares control arm information across the platform, and (iii) uses a time-to-event endpoint with a formal testing structure and error control for evaluation of potential efficacy. Both single-agent and combination treatments are considered. We find that the design can identify potential treatments that are safe and efficacious reliably with small to moderate sample sizes.

Impact of pharmaceutical and non-pharmaceutical interventions on COVID-19 in Tunisia

BackgroundIn COVID-19 management, a variety of pharmaceutical interventions (PI) and non- pharmaceutical interventions (NPI) were adopted to limit the spread of the disease and its associated deaths. We aimed to evaluate the impact of PI and NPI on risks of COVID-19 transmission and deaths.MethodWe collected aggregate data from March 2nd, 2020, to December 1, 2022 from the Tunisian Ministry of Health's website and OurWorldInData.org site. NPI Periods (NPIP: March 2020 to March 2021) and PI Periods (PIP) were distributed to NPIP1, 2, 3 and 4 and to PIP1, 2, 3 and 4, respectively. We calculated the Relative Risks (RR) and 95% Confidence Intervals (CI) by comparing the subsequent period with previous one.ResultsThe risk of SARS-CoV-2 transmission increased progressively from the zero cases period (NPIP2) to the mitigate strategy period (NPIP3) (RR = 14.0; 95% CI: 12.4–15.8) and to the stop-and-go epidemic control period (NPIP4) (RR = 23.1 (95% CI: 22.4–23.9). It was stabilized in the targeted vaccination period (PIP1) (RR = 1.08, 95% CI: 1.07–1.08) and reduced during the mass vaccination period (PIP2) (RR: 0.50, 95% CI: 0.50–0.51). SARS-CoV-2 transmission, increased during PIP3 concomitant with the Omicron wave (RR = 2.65, 95% CI: 2.64–2.67). It remained at a low level in PIP4 (RR = 0.18; 95% CI: 0.18–0.18).Compared to NPIP2, NPIP3 and NPIP4 were associated with a higher risk of COVID-19 mortality (RR = 3.337; 95% CI: 1.797–6.195) and (RR = 72.63 (95% CI: 54.01–97.68), respectively. Since the start of the immunization program, the risk of COVID-19 death has consistently decreased. In comparison to each previous period, the risk transitioned in PIP1 to RR = 0.91; 95% CI: 0.88–0.93, then to RR = 0.85; 95% CI: 0.83–0.88 in PIP2, to RR = 0.47; 95% CI: 0.45–0.50 in PIP3, and to RR = 0.19; 95% CI: 0.18–0.24 during PIP4.ConclusionIn terms of lowering the risk of transmission and mortality, the NP strategy at the beginning of the epidemic outperformed the IP strategy during the outbreak.

Engaging with Social Media: Implications for COVID-19 Research Participation Among Adults Living in the State of Florida.

The COVID-19 pandemic led to an increased use of social media, with many people turning to it for social support. Given the varying effects of social media, this study examines how social media use influences the willingness of adults in the State of Florida to participate in COVID-19-related research. The study used data collected through the Florida Statewide Registry for Aging Studies (FSRAS), which included 587 participants who were 25 years and older. The primary outcome variables were COVID-19 treatment and COVID-19 vaccine research. Ordinal logistic regression was used to evaluate the association between social media use and willingness to participate in COVID-19 treatment and vaccination research, adjusting for sociodemographic variables. The analysis did not find a statistically significant relationship between social media use and the likelihood of participating in COVID-19 research. However, significant differences were observed across racial/ethnic groups. Participants who identified as "Hispanic/Latino" (OR-2.44, 95% CI-1.11-5.35, p = 0.03) and "Other" (OR-12.51, 95% CI-1.98-79.22, p = 0.01) were significantly associated with willingness to participate in a COVID-19 treatment research. Similarly, participants of all other races/ethnicities were significantly more willing to participate in research testing COVID-19 vaccines. Additionally, females were more likely to express willingness to participate in COVID-19 vaccine research. Social media use did not significantly affect willingness to participate in COVID-19 treatment and vaccine research; however, racial and ethnic differences significantly influenced willingness to participate. These findings suggest that implementing targeted culturally sensitive recruitment strategies and community engagement efforts can improve participation in COVID-19 research.

The Impact of Infliximab on Hyperinflammation State in Hospitalized COVID-19 Patients: A Retrospective Study

Background and Objectives: Elevated levels of pro-inflammatory cytokines have been linked to increased mortality in COVID-19 patients. Infliximab, a tumor necrosis factor inhibitor, has been reported to improve outcomes in COVID-19 patients by targeting the hyperinflammatory response. Our objective was to evaluate the effectiveness of incorporating Infliximab into standard care guidelines for the management of COVID-19. Materials and Methods: A retrospective analysis was conducted on 111 participants who were moderate to severe COVID-19 patients admitted to the hospital. Among them, 74 individuals received solely standard treatment, while 37 received standard therapy plus Infliximab. The primary outcomes of the study centered around the changes in laboratory test parameters. The secondary clinical findings included clinical recovery defined as improvement in patient oxygenation, time till recovery, and assessing necessity for ICU admission, and mortality rates. Results: There was no statistical difference observed in the inflammatory markers including, LDH, Ferritin, CRP, neutrophil to lymphocyte ratio (NLR), and P/F ratio between both groups and in the clinical outcomes including clinical recovery (p = 1.0), time to improvement (p = 0.436), and mortality rate (p = 0.601). However, there was a significant increase in secondary infection (45.9%, 20.3%; p = 0.005), and in liver enzymes, ALT (79.5, 50.0 IU/L; p = 0.02) and AST (57.5, 38.0 IU/L; p = 0.019) in the Infliximab group and the standard care group, respectively. Conclusions: Infliximab therapy did not demonstrate significant benefits compared to standard of care in moderate to severe hospitalized COVID-19 patients.

Impact of early antiviral therapy on SARS-CoV-2 clearance time in high-risk COVID-19 subjects: A propensity score matching study

BackgroundEffective treatments for COVID-19 are needed to mitigate disease progression and reduce the burden on healthcare systems. This study investigates the impact of early treatments on SARS-CoV-2 viral shedding duration among high-risk individuals with mild symptoms. MethodsA single-center, retrospective observational study was conducted at Luigi Sacco Hospital in Milan from December 2021 to March 2023. Hospitalized and nonhospitalized adults with a confirmed SARS-CoV-2 infection and at high-risk of disease progression were enrolled. Unadjusted and adjusted negative binomial regression models and a Random Forest regression model were performed before and after matching subjects based on their propensity of being treated or not. ResultsResults from 518 subjects (428 treated and 90 untreated) revealed a significant reduction in SARS-CoV-2 viral shedding duration among those who received early treatment compared to untreated individuals. Propensity score matching and multivariable regression analyses confirmed this finding. Early treatment significantly reduced the risk of COVID-19-related hospitalization and pneumonia development. Subgroup analysis identified COPD as a potential factor influencing effectiveness of early treatments. ConclusionsEarly treatments play a crucial role in reducing SARS-CoV-2 viral shedding and preventing disease progression among high-risk individuals. Shorter viral shedding duration also contributes to improved healthcare resource utilization and infection control measures.

Molecular Mechanism-Driven Discovery of Novel Small Molecule Inhibitors against Drug-Resistant SARS-CoV-2 Mpro Variants.

Under the selective pressure of nirmatrelvir, a peptidomimetic covalent drug targeting SARS-CoV-2 Mpro, various drug-resistant mutations on Mpro have been acquired in vitro. Among the mutations, L50F and E166V, along with the combination of L50F and E166V, are particularly representative and pose considerable obstacles to the effective treatment of COVID-19. Our previous study identified NMI-001 and NMI-002 as novel nonpeptide inhibitors that target SARS-CoV-2 Mpro, possessing unique scaffolds and binding modes different from those of nirmatrelvir. In view of these findings, we proposed a drug design strategy aimed at rapidly identifying inhibitors that can combat mutation-induced drug resistance. Initially, molecular dynamics (MD) simulation was employed to investigate the binding mechanisms of NMI-001 and NMI-002 against the three drug-resistant mutants (Mpro_L50F, Mpro_E166V, and Mpro_L50F+E166V). Then, we conducted two phases of high-throughput virtual screening. In the first phase, NMI-001 served as a template to perform scaffold hopping-based similarity search in a library of 15,742,661 compounds. In the second phase, 968 compounds exhibiting similarity to NMI-001 were evaluated via molecular docking and MD simulations. Six compounds that may be effective against at least one mutant were identified, and five compounds were procured for conducting in vitro assays. Finally, the compound Z1557501297 (NMI-003) exhibiting inhibitory effects against the E166V (IC50 = 27.81 ± 2.65 μM) and L50F+E166V (IC50 = 8.78 ± 0.74 μM) mutants was discovered. The binding modes referring to NMI-003-Mpro_E166V and NMI-003-Mpro_L50F+E166V were further elucidated at the atomic level. In summary, NMI-003 reported herein is the first compound with activity against E166V and L50F+E166V, which provides a good starting point to design novel antiviral drugs for the treatment of drug-resistant SARS-CoV-2.

Does Remdesivir Lower COVID-19 Mortality? A Subgroup Analysis of Hospitalized Adults Receiving Supplemental Oxygen.

The first Adaptive COVID-19 Treatment Trial (ACTT-1) showed that remdesivir improved COVID-19 recovery time compared with placebo in hospitalized adults. The secondary outcome of mortality was almost significant overall (p = 0.07) and highly significant for people receiving supplemental oxygen at enrollment (p = 0.002), suggesting a mortality benefit concentrated in this group. We explore analysis methods that are helpful when a single subgroup benefits from treatment and apply them to ACTT-1, using baseline oxygen use to define subgroups. We consider two questions: (1) is the remdesivir effect for people receiving supplemental oxygen real, and (2) does this effect differ from the overall effect? For Question 1, we apply a Bonferroni adjustment to subgroup-specific hypothesis tests and the Westfall and Young permutation test, which is valid when small cell counts preclude normally distributed test statistics (a frequently unexamined condition in subgroup analyses). For Question 2, we introduce Qmax, the largest standardized difference between subgroup-specific effects and the overall effect. Qmax simultaneously tests whether any subgroup effect differs from the overall effect and identifies the subgroup benefitting most. We demonstrate that Qmax strongly controls the familywise error rate (FWER) when test statistics are normally distributed with no mean-variance relationship. We compare Qmax to a related permutation test, SEAMOS, which was previously proposed but not extensively applied or tested. We show that SEAMOS can have inflated Type 1 error under the global null when control arm event rates differ between subgroups. Our results support a mortality benefit from remdesivir in people receiving supplemental oxygen.

The Impact of Tocilizumab Coverage on Health Equity for Inpatients with COVID-19 in the USA: A Distributional Cost-Effectiveness Analysis.

We conducted a distributional cost-effectiveness analysis to evaluate how coverage of tocilizumab for inpatients with COVID-19 from 2021 to present impacted health equity in the USA. A published, payer-perspective, distributional cost-effectiveness analysis for inpatient COVID-19 treatments was adapted to include information on baseline health disparities across 25 equity-relevant subgroups based on race and ethnicity (5 census-based groups), and county-level social vulnerability (5 geographic quintiles). The underlying cost-effectiveness analysis was updated to reflect patient characteristics at admission, standard of care outcomes, tocilizumab efficacy, and contemporary unit costs. The distributional cost-effectiveness analysis inputs for COVID-19 hospitalization and subgroup risk adjustments based on social vulnerability were derived from published estimates. Opportunity costs were estimated by converting total tocilizumab spend into quality-adjusted life-years (QALYs), distributed equally across subgroups. Tocilizumab treatment was cost effective across all subgroups. Treatment resulted in larger relative QALY gains in more socially vulnerable subgroups than less socially vulnerable subgroups, given higher hospitalization rates and inpatient mortality. Using an opportunity cost threshold of US$150,000/QALY and an Atkinson index of 11, tocilizumab was estimated to have improved social welfare by increasing population health (53,252 QALYs gained) and reducing existing overall US health inequalities by 0.003% since 2021. Use of tocilizumab for COVID-19 since 2021 increased population health while improving health equity, as more patients with lower baseline health were eligible for treatment and received larger relative health gains. Future equitable access to tocilizumab for inpatients with COVID-19 is expected to lead to continued increases in population health and reductions in disparities.

Identification of a potent SARS-CoV-2 neutralizing nanobody targeting the receptor-binding domain of the spike protein

SARS-CoV-2 and its variants continue to pose a significant threat to public health. Nanobodies (Nbs) that inhibit the interaction between the receptor-binding domain (RBD) of the spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2) are promising drug candidates. In this study, we report the discovery and structural characterization of a potent Nb that targets the RBD. By screening a phage display alpaca naive Nbs library using the RBD as bait, we identified sixteen candidate Nbs. Of these, nine exhibited nanomolar to micromolar binding affinity and strong neutralizing activity against pseudotyped SARS-CoV-2 viruses, with NbS4 showing the highest neutralization potency. The crystal structure of the SARS-CoV-2 RBD in complex with NbS4 revealed that this Nb binds to a site partially overlapping the ACE2 binding region. Importantly, the key binding residues of NbS4 in the RBD are conserved across most known variants, making it a promising candidate for COVID-19 treatment.

Probiotic interventions and quality of life in patients with gastrointestinal diseases: A comprehensive review.

Gastrointestinal disorders manifest through disruptions in gastrointestinal functionality accompanied by dysbiosis within the microbiome. Probiotics are considered biological agents with potential therapeutic efficacy in managing gastrointestinal pathologies by modulating the gut microbiota. Nevertheless, several hurdles, such as safety considerations, resilience to stressors, post-colonization quantifications, and evaluative modalities, may impede the adoption of probiotics for gastrointestinal disorders. Herein, we performed online research using 6 databases: Scopus, ScienceDirect, PubMed, Web of Science, Cochrane Library, and Ovid. Inclusion criteria were mostly articles published in the years 2015-2024, concerning the association between probiotics and gastrointestinal diseases. This review aimed to provide comprehensive data regarding the latest studies in this area. Additionally, this review delineates the various aspects of probiotic use, including both the positive and negative aspects, as well as the role of probiotics in immune system modulation and the prevention of various diseases. Also, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics in the management of COVID-19. Given the extensive adoption of probiotic formulations as microecological interventions for gastrointestinal disorders, a comprehensive understanding of the challenges inherent in their application and the implementation of contemporary methodologies to enhance probiotic colonization and evaluation systems are paramount for harnessing probiotics as viable biotherapeutic agents. However, there is a need for additional studies to confirm the potential role of probiotics as a suitable target in the treatment of gastrointestinal diseases.

Case Study – Fully Recovered After 3.5 Years of Long COVID

The purpose of this paper is to explain the path this Long Covid patient took to become 100 % cured from Long COVID.. Certainly in the early years of the Covid 19 pandemic, Long COVID was not yet well known and there was no recognized treatment for Long COVID. Even today, there are no validated effective treatments. This women was healthy prior to the infection and did not suffer from chronic conditions. Long COVID turned out to be a rather neurological/immunological disorder in this PostLong COVID patient (from the end of Feb. '20 to Oct. ‘23). Promising positive results, via a new 'soft trial approach' of the autonomic nervous system out of balance, have led to a cure for the Long COVID symptoms with, among other things, PEM. This after 3.5 years.Since then, until today, September 2024, there has been no relapse. She has been 100% active again since the summer of 2023 as she was before the first Covid infection.

COVID-19 Therapeutics for Nonhospitalized Older Adults

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

Management of COVID-19 patients of CT Severity 15/25 and above with Ayurveda drugs as add-on therapy – A Case Series

Ayurveda, which is the oldest life science in the world, has yet to be fully accepted as the only or even an additional therapy for severe diseases. It is a common perception that Ayurveda has a significant role in the preventive aspect of diseases, and the drugs of Ayurveda are more effective in chronic ailments. Most publications are also limited to these areas only, as use of Ayurveda in acute or severe cases is not yet justified scientifically because of the lack of significant scientific clinical data as very few case reports are published about the use of Ayurveda in acute cases. Here we present a case series of treatment of five COVID-19 patients with CT Severity 15/25 and above with Ayurveda drugs as add-on therapy admitted to tertiary care, a Level-3 COVID-19 treatment hospital. These five patients sought Ayurveda opinion and consented to Ayurveda treatment along with the ongoing treatment regime. All the patients showed improvement with Ayurveda treatment as an add-on therapy, and none of the patients needed ICU, and all patients were discharged when they started maintaining oxygen saturation at room air. This report addresses the clinical effectiveness of Ayurveda drugs as add-on therapy in severe cases of COVID -19. It also attempts to invite the attention of researchers towards the use of Ayurveda concepts and drugs in severe or acute cases of diseases.

A Lean Six Sigma approach aided improvement for simultaneous electrochemical determination of antiviral drug favipiravir and levodropropizine as an option in the treatment of COVID-19 using glassy carbon electrode modified NiFe2O4 nanocomposite in different matrices

Favipiravir (FPV) is a widely used drug that works well against a variety of infectious RNA viruses. It is commonly used as an anti-influenza medication. To treat patients infected with RNA viruses, combination therapy consisting of FPV and levodropropizine (LDP) is required. As a result, an effective electrochemical sensor for identifying FPV in human plasma samples has been developed. The hydrothermal method is used to synthesize NiFe2O4NPs, a binary transition metal oxide comprising iron and nickel. The effective synthesis of these materials is verified by energy-dispersive X-ray analysis (EDX) and X-ray diffraction (XRD). The developed nanocomposite underwent physicochemical and electrochemical characterization, and the experimental setup was refined. Two broad linear dynamic ranges were obtained for both medications using Differential Pulse Voltammetry (DPV): 0.5 µM–200 µM for FPV and 1.0 µM–110 µM for LDP. For FPV, the computed detection and quantitation limits were 0.148 µM and 0.45 µM, while for LDP, they were 0.297 µM and 0.9 µM. The recommended technique was successfully used to analyze both medications at the same time in human plasma samples, and acceptable percentage recoveries were attained. In terms of greenness, EcoScale and GAPI greenness tools were used to evaluate the analytical methodology. Additional studies on repeatability, stability testing, interference analysis, and greenness evaluation supported the validity of the recommended method for the simultaneous measurement of FPV and LDP in laboratories for quality assurance. Additionally, Lean Six Sigma (LSS) quality technique is regarded as a collection of management disciplines for continuous improvement and method control. It is thought to offer the most practical way to address the negative effects of variation by taking steps toward analytical process improvement. As a result, LSS can be considered an invaluable tool in any laboratory, serving as a standard method for process optimization and problem solutions as well as a managerial discipline. Furthermore, it guarantees a strong method specification at a high degree of statistical confidence and targeted performance.