Reaction Pattern and Mechanistic Aspects of Iodine and Iodine-Based Reagents in Selenylation of Aliphatic, Aromatic, and (Hetero)Cyclic Systems.

Organoselenium compounds have been the subject of extensive research since the discovery of the biologically active compound ebselen. Ebselen has recently been found to show activity against the main protease of the virus responsible for COVID-19. Other organoselenium compounds are also well-known for their diverse biological activities, with such compounds exhibiting interesting physical properties relevant to the fields of electronics, materials, and polymer chemistry. In addition, the incorporation of selenium into various organic molecules has garnered significant attention due to the potential of selenium to enhance the biological activity of these molecules, particularly in conjunction with bioactive heterocycles. Iodine and iodine-based reagents play a prominent role in the synthesis of organoselenium compounds, being valued for their cost-effectiveness, non-toxicity, and ease of handling. These reagents efficiently selenylate a broad range of organic substrates, encompassing alkenes, alkynes, and cyclic, aromatic, and heterocyclic molecules. They serve as catalysts, additives, inducers, and oxidizing agents, facilitating the introduction of different functional groups at alternate positions in the molecules, thereby allowing for regioselective and stereoselective approaches. Specific iodine reagents and their combinations can be tailored to follow the desired reaction pathways. Here, we present a comprehensive review of the progress in the selenylation of organic molecules using iodine reagents over the past decade, with a focus on reaction patterns, solvent effects, heating, microwave, and ultrasonic conditions. Detailed discussions on mechanistic aspects, such as electrophilic, nucleophilic, radical, electrochemical, and ring expansion reactions via selenylation, multiselenylation, and difunctionalization, are included. The review also highlights the formation of various cyclic, heterocyclic, and heteroarenes resulting from the in situ generation of selenium intermediates, encompassing cyclic ketones, cyclic ethers, cyclic lactones, selenophenes, chromones, pyrazolines, pyrrolidines, piperidines, indolines, oxazolines, isooxazolines, lactones, dihydrofurans, and isoxazolidines. To enhance the reader's interest, the review is structured into different sections covering the selenylation of aliphatic sp2/sp carbon and cyclic sp2 carbon, and then is further subdivided into various heterocyclic molecules.

Synergistic photoinduced charge transfer resonance from porous ZIF-67 decorated violet phosphorus array for SERS immunoassay of SARS-CoV-2 spike protein.

As a rapid, highly sensitive, and user-friendly technique, surface-enhanced Raman scattering (SERS) has an extraordinary appeal to home self-test of COVID-19 during the post pandemic era. However, most of the existing SERS substrates have been still criticized in stability, repeatability, and sample enrichment. To address these obstacles, a novel non-metallic SERS substrate with porous surfaces and array geometry was developed by in-situ growing ZIF-67 particles on two-dimensional violet phosphorus (VP) matrix. Chemical enhancement was prominently promoted by the synergistic photoinduced charge transfer resonance in the hybrid band structure of the ZIF-67@VP substrate, facilitating a noble metal-similar enhancement factor of 6.11 × 107. The biocompatible ZIF-67@VP porous array with attractive enhancement capability and high anchoring efficiency was further utilized to monitoring SARS-CoV-2 spike protein in practical saliva samples based on a sandwich immunostructure, achieving a limit of detection of 1.7 ng/mL assisted by black phosphorus nanosheets. This nonmetallic immunoassay strategy with exceptional sensitivity and specificity is predicted to extend the utilization of SERS obstacle in daily infectious disease screening.

Micronutrient Status of Critically Ill Patients with COVID-19 Pneumonia.

Micronutrient deficiencies can develop in critically ill patients, arising from factors such as decreased intake, increased losses, drug interactions, and hypermetabolism. These deficiencies may compromise important immune functions, with potential implications for patient outcomes. Alternatively, micronutrient blood levels may become low due to inflammation-driven redistribution rather than consumption. This explorative pilot study investigates blood micronutrient concentrations during the first three weeks of ICU stay in critically ill COVID-19 patients and evaluates the impact of additional micronutrient administration. Moreover, associations between inflammation, disease severity, and micronutrient status were explored. We measured weekly concentrations of vitamins A, B6, D, and E; iron; zinc; copper; selenium; and CRP as a marker of inflammation state and the SOFA score indicating disease severity in 20 critically ill COVID-19 patients during three weeks of ICU stay. Half of the patients received additional (intravenous) micronutrient administration. Data were analyzed with linear mixed models and Pearson's correlation coefficient. High deficiency rates of vitamins A, B6, and D; zinc; and selenium (50-100%) were found at ICU admission, along with low iron status. After three weeks, vitamins B6 and D deficiencies persisted, and iron status remained low. Plasma levels of vitamins A and E, zinc, and selenium improved. No significant differences in micronutrient levels were found between patient groups. Negative correlations were identified between the CRP level and levels of vitamins A and E, iron, transferrin, zinc, and selenium. SOFA scores negatively correlated with vitamin D and selenium levels. Our findings reveal high micronutrient deficiency rates at ICU admission. Additional micronutrient administration did not enhance levels or expedite their increase. Spontaneous increases in vitamins A and E, zinc, and selenium levels were associated with inflammation resolution, suggesting that observed low levels may be attributed, at least in part, to redistribution rather than true deficiencies.

Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.

Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix. Here, we assess the potential of protease inhibitors (PI) derived from potatoes in inhibiting viral infection and reducing tissue damage. The original full spectrum of potato PI was developed into five fractions by means of chromatography and hydrolysis. Individual fractions showed varying inhibitory efficacy towards a panel of proteases including trypsin, chymotrypsin, ACE2, elastase, and cathepsins B and L. The fractions did not interfere with SARS-CoV-2 infection of Vero E6 cells in vitro. Importantly, two of the fractions fully inhibited elastin-degrading activity of complete primary human neutrophil degranulate. These data warrant further development of potato PI fractions for biomedical purposes, including tissue damage crucial to SARS-CoV-2 pathogenesis. KEY MESSAGES: Protease inhibitor fractions from potato differentially inhibit a series of human proteases involved in viral replication and in tissue damage by overshoot inflammation. Protease inhibition of cell surface receptors such as ACE2 does not prevent virus infection of Vero cells in vitro. Protease inhibitors derived from potato can fully inhibit elastin-degrading primary human neutrophil proteases. Protease inhibitor fractions can be produced at high scale (hundreds of thousands of kilograms, i.e., tons) allowing economically feasible application in lower and higher income countries.

Clinical Evidence on the Potential Beneficial Effects of Diet and Dietary Supplements against COVID-19 Infection Risk and Symptoms' Severity.

BACKGROUND: Diet and dietary supplements aim to add trace elements, vitamins, and minerals to the body to improve human health and boost the immune system. In the previous few years, the new SARS-CoV-2 coronavirus strain has been threatening the health of individuals and public health more broadly, with rates of intensive care unit cases on the rise, while long-term COVID-19 complications are persisting until today. In the peculiar circumstances of the COVID-19 pandemic, in combination with disease prevention techniques, the strengthening of the immune system is considered particularly important to enable it to effectively respond to and eliminate the SARS-CoV-2 viral pathogen in the event of infection. The purpose of the current literature review is to thoroughly summarize and critically analyze the current clinical data concerning the potential beneficial effects of diet and dietary supplements against COVID-19 infection risk and symptoms' severity. The micronutrients/supplements examined in this study in relation to COVID-19 infection are vitamins A, B, C, and D, zinc, selenium, magnesium, iron, omega-3 fatty acids, glutamine, resveratrol, beta-glucans, and probiotics. The potential effects of dietary patterns such as the Mediterranean diet against SARS-CoV-2 infection risk and symptoms' severity were also analyzed. Our literature review suggests that micro- and macronutrient supplementation and a healthy diet and lifestyle may provide support to immune system function, with beneficial effects both before and during SARS-CoV-2 infection. However, additional studies are recommended to draw safe conclusions and formulate dietary recommendations concerning dietary supplements and their possible effects on preventing and co-treating COVID-19 disease.

Identifying dynamic risk spillovers between crude oil and downstream industries: China's futures market perspective.

Interactions between crude oil and its downstream products are crucial but complex. The main purpose of this study is to examine the risk spillover relationships between the crude oil futures market and the petrochemical downstream futures market in the context of the COVID-19 epidemic in China. By combining the dynamic conditional correlation-generalized autoregressive conditional heteroskedasticity (DCC-GARCH) model and the Diebold-Yilmaz spillover index based on time-varying parameter-vector autoregression (TVP-VAR-DY), we investigate the dynamic correlations between Shanghai crude oil futures (INE) and the downstream futures in China's petrochemical industry chain. At the same time, we also incorporate the representative global crude oil futures (BRENT and WTI) in our study as a comparative analysis. Our results show a significant positive correlation between three crude oil futures and China's downstream future products, with a more pronounced link observed between INE and the downstream futures market. Moreover, the correlation between crude oil futures and various downstream products exhibits heterogeneity; that is, direct derivatives of crude oil show higher sensitivity to price fluctuations compared to products with longer production chains. Furthermore, the spillover results indicate that the international crude oil futures, particularly BRENT, primarily function as spillover transmitters, while INE mainly serves as the recipient. In the post-pandemic period, the international crude oil market still exhibits a high spillover effect, and the spillover effect of INE to polyvinyl chloride, pure terephthalic acid, and bitumen futures increased, reflecting market recovery in China to some extent. These results provide potential insights for policymakers, financial institutions, industry participants, and investors, emphasizing the importance of enhanced risk management, diversified investment strategies, and attention to market dynamics.

Alertas sanitarias de productos médicos subestándares, falsificados y no registrados al inicio de la pandemia de COVID-19 en las Américas / Health alerts for substandard, falsified, and unregistered medical products at the onset of the COVID-19 pandemic in the Americas / Alertas de saúde para produtos médicos abaixo do padrão, falsificados e não registrados no início da pandemia de COVID-19 nas Américas

[RESUMEN]. Objetivo. Identificar y analizar los incidentes de productos médicos subestándares, falsificados, no registrados y robados al inicio de la pandemia de COVID-19. Métodos. Búsqueda detallada en los sitios web de las autoridades reguladoras de las Américas. Identificación de los incidentes de medicamentos y dispositivos médicos (incluidos los de diagnóstico in vitro) subestándares falsificados, no registrados y robados. Se determinaron los tipos de productos, las etapas de la cadena de suministro en las que se detectaron y las medidas tomadas por las autoridades. Resultados. Se identificaron 1 273 incidentes en 15 países (1 087 productos subestándares, 44 falsificados, 123 no registrados y 19 robados). La mayor cantidad de incidentes corresponden a dispositivos médicos, desinfectantes y antisépticos. El punto en la cadena de suministro con mayor frecuencia de informes fue la adquisición a través de internet. Las medidas tomadas por las autoridades reguladoras corresponden en su mayoría a: alerta, prohibición de uso, prohibición de publicidad y fabricación, retiro del mercado y seguimiento de eventos adversos. Conclusiones. Se evidenció un número destacable de incidentes de productos médicos subestándares, falsificados, no registrados y robados al inicio de la pandemia por COVID-19. La escasez de insumos, la flexibilización en los requisitos regulatorios y el aumento de la demanda son factores que pueden favorecer el incremento del número de incidentes. Las autoridades reguladoras nacionales de referencia presentaron mayores frecuencias de detección de incidentes y de aplicación de medidas sanitarias. Se observó que se debe abordar el canal de venta por internet con alguna estrategia reguladora para garantizar la distribución segura de productos médicos.

[ABSTRACT]. Objective. Identify and analyze incidents of substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic. Methods. Detailed search of the websites of regulatory authorities in the Americas. Identification of incidents of substandard, falsified, unregistered, and stolen medicines and medical devices (including in vitro diagnostics). The types of products were determined, as were the stages in the supply chain where they were detected, and the actions taken by authorities. Results. A total of 1 273 incidents were identified in 15 countries (1 087 substandard, 44 falsified, 123 unreg- istered, and 19 stolen products). The largest number of incidents involved medical devices, disinfectants, and antiseptics. The most frequently reported point in the supply chain was online purchasing. The principal measures taken by the regulatory authorities were: alerts, prohibition of use, prohibition of advertising and manufacture, recall, and monitoring of adverse events. Conclusions. A substantial number of incidents involving substandard, falsified, unregistered, and stolen medical products at the onset of the COVID-19 pandemic were identified. Shortages of supplies, easing of regulatory requirements, and increased demand are factors that may have led to an increase in the number of incidents. The national regulatory authorities of reference reported more frequent detection of incidents and more frequent application of health measures. A regulatory strategy is needed in order to address online sales and ensure the safe distribution of medical products.

[RESUMO]. Objetivo. Identificar e analisar incidentes de produtos médicos abaixo do padrão, falsificados, não registrados e roubados no início da pandemia de COVID-19. Métodos. Foi realizada uma busca detalhada nos sites das autoridades reguladoras das Américas. Foram identificados incidentes envolvendo medicamentos e dispositivos médicos (incluindo para diagnóstico in vitro) abaixo do padrão, falsificados, não registrados e roubados. Foram determinados os tipos de produtos, os estágios da cadeia de abastecimento em que foram detectados e as medidas tomadas pelas autoridades. Resultados. Foram identificados 1 273 incidentes em 15 países (1 087 produtos abaixo do padrão, 44 falsificados, 123 não registrados e 19 roubados). O maior número de incidentes estava relacionado a dispositivos médicos, desinfetantes e antissépticos. O ponto na cadeia de abastecimento com a maior frequência de relatos foi a de aquisição pela internet. As medidas tomadas pelas autoridades reguladoras foram principalmente alertas, proibições de uso, proibições de publicidade e fabricação, recolhimento de produtos do mercado e monitoramento de eventos adversos. Conclusões. Houve um número significativo de incidentes envolvendo produtos médicos abaixo do padrão falsificados, não registrados e roubados no início da pandemia de COVID-19. A escassez de insumos, a flexibilização das exigências regulatórias e o aumento da demanda são fatores que podem levar a um maior número de incidentes. As autoridades reguladoras nacionais de referência informaram um aumento na frequência de detecção de incidentes e implementação de medidas sanitárias. O canal de vendas pela internet precisa ser abordado com alguma estratégia regulatória para garantir a distribuição segura de produtos médicos.

Pregnant women's attitudes towards complementary and alternative medicine and the use of phytotherapy during the COVID-19 pandemic: A cross-sectional study.

BACKGROUND: Approximately 80% of individuals worldwide use various holistic complementary and alternative medicine (HCAM) methods, including herbal products, to prevent diseases and improve their general health. In this study, it was aimed to investigate complementary and alternative therapy (CAM) and the use of phytotherapy by pregnant women in the COVID-19 pandemic period. METHODS: This is a cross-sectional and descriptive study. The study included 381 women who applied to a public hospital in Türkiye and used herbal products during this pregnancy. Purposive sampling method was used. The study data were collected through "Identifying Information Form", "Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ)" and "Information Form on the Use of Phytotherapy". In the analysis of the study data, descriptive statistics, the one-way ANOVA and multinomial logistic regression analyses were used. RESULTS: The study was completed with 381 pregnant women. The average age, parity and gestational age of the pregnant women were 28.33±6.09, 2.17±0.95, 29.11±8.87, respectively. It was determined that 37.3% of pregnant women did not know the ingredients of the herbal products they used and 38.8% found them safer than the drugs. HCAMQ total mean score of the pregnant women was calculated as 34.62±16.22. It was found that the pregnant women used garlic the most (65.6%), followed by cumin (38.6%), curcuma (36.2%), and ginger (34.4%). HCAMQ total mean score was found to be lower in the pregnant women who found herbal products safer than drugs (p<0.001), who were not aware of the content of the herbal product they used (p<0.001), and who used herbal products so as to protect against COVID-19 (p = 0.041), to increase their physical resistance (p = 0.022), and to facilitate childbirth (p = 0.002). It was determined that among the pregnant women who knew the content of the herbal products they used (Odds Ratio (OR) 1.122; 1.095-1.149 95%CI; p<0.001) and who did not know (OR 1.114; 1.085-1.144 95%CI; p<0.001), as negative attitude towards HCAM increased, their status of finding traditional drugs safer increased. Among the pregnant women who used herbal products to protect against COVID-19 (OR 1.142; 1.111-1.174 95%CI; p<0.001) and to increase their physical resistance (OR 1.120; 1.094-1.147 95%CI; p<0.001), as negative attitude towards HCAM increased, their status of finding conventional drugs safer increased. CONCLUSION: In today's world where the use of herbal products and CAM has become widespread, it is important to raise the awareness of pregnant women about the benefits and harms of these practices about which there is inadequate evidence.

Leveraging SARS-CoV-2 Main Protease (Mpro) for COVID-19 Mitigation with Selenium-Based Inhibitors.

The implementation of innovative approaches is crucial in an ongoing endeavor to mitigate the impact of COVID-19 pandemic. The present study examines the strategic application of the SARS-CoV-2 Main Protease (Mpro) as a prospective instrument in the repertoire to combat the virus. The cloning, expression, and purification of Mpro, which plays a critical role in the viral life cycle, through heterologous expression in Escherichia coli in a completely soluble form produced an active enzyme. The hydrolysis of a specific substrate peptide comprising a six-amino-acid sequence (TSAVLQ) linked to a p-nitroaniline (pNA) fragment together with the use of a fluorogenic substrate allowed us to determine effective inhibitors incorporating selenium moieties, such as benzoselenoates and carbamoselenoates. The new inhibitors revealed their potential to proficiently inhibit Mpro with IC50-s in the low micromolar range. Our study contributes to the development of a new class of protease inhibitors targeting Mpro, ultimately strengthening the antiviral arsenal against COVID-19 and possibly, related coronaviruses.

Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have shown that hydroxychloroquine (HCQ) significantly inhibits SARS-CoV-2 infections in vitro. OBJECTIVE: Since the phytoconstituents of Cinchona officinalis (CO) are similar to those of HCQ, the objective of this study was to test the antiviral potential of different homeopathic formulations of CO. METHODS: An analysis of the molecular composition of CO was carried out using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by a detailed docking study. The constituents of CO were docked against various targets of SARS-CoV-2, and the binding potential of the phytoconstituents was compared and quantified. The ligand with the lowest Glide docking score is considered to have the best binding affinity. The cytotoxicity of several homeopathic formulations, including CO mother tincture (CO-MT), was also checked on VeroE6 cells. A known antiviral, remdesivir, was used as a positive control for the in vitro assays to evaluate the effects of CO-MT against SARS-CoV-2-infected VeroE6 cells. RESULTS: Molecular docking studies showed that constituents of CO exhibited binding potential to various targets of SARS-CoV-2, including Mpro, PLpro, RdRp, nucleocapsid protein, ACE2 (in host) and spike protein. Quinoline, one of the constituents of CO, can potentially bind the spike protein of SARS-CoV-2. Quinic acid showed better binding capabilities with Mpro, PLpro RdRp, nucleocapsid protein and ACE2 (allosteric site) than other constituents. Quinidine exhibited better binding to ACE2. Compared to HCQ, other phytoconstituents of CO had the equivalent potential to bind the RNA-dependent RNA polymerase, nucleocapsid protein, Mpro, PLpro and spike protein of SARS-CoV-2. In vitro assays showed that homeopathic CO-MT was not cytotoxic and that CO-MT and remdesivir respectively caused 89% and 99% inhibition of SARS-CoV-2 infection in VeroE6 cells. CONCLUSION: Based on this in silico and in vitro evidence, we propose CO-MT as a promising antiviral medicine candidate for treating COVID-19. In vivo investigation is required to clarify the therapeutic potential of CO-MT in COVID-19.

Therapeutic potential and possible mechanisms of ginseng for depression associated with COVID-19.

Recently, a global outbreak of COVID-19 has rapidly spread to various national regions. As the number of COVID-19 patients has increased, some of those infected with SARS-CoV-2 have developed a variety of psychiatric symptoms, including depression, cognitive impairment, and fatigue. A distinct storm of inflammatory factors that contribute to the initial disease but also a persistent post-acute phase syndrome has been reported in patients with COVID-19. Neuropsychological symptoms including depression, cognitive impairment, and fatigue are closely related to circulating and local (brain) inflammatory factors. Natural products are currently being examined for their ability to treat numerous complications caused by COVID-19. Among them, ginseng has anti-inflammatory, immune system stimulating, neuroendocrine modulating, and other effects, which may help improve psychiatric symptoms. This review summarizes the basic mechanisms of COVID-19 pneumonia, psychiatric symptoms following coronavirus infections, effects of ginseng on depression, restlessness, and other psychiatric symptoms associated with post-COVID syn-dromes, as well as possible mechanisms underlying these effects.

The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

Alternative therapies for viral infections caused by SARS-Cov-2 / Terapias alternativas para infecções virais causadas pelo SARS-Cov-2

Abstract Introduction The relevance of the studied topic lies in the complexity of the treatment of infection caused by SARS-CoV-2. Objective To discuss the potential advantages and disadvantages of alternative treatments compared to conventional medical approaches, and to highlight the importance of collaborative communication between patients and healthcare providers in making informed decisions about alternative treatments of the SARS-CoV-2 virus. Methods The research methodology employed literature analysis methods, including bibliographic and bibliosemantic approaches. The study used theoretical, systematic, and statistical methods, including analysis, synthesis, generalization, interpretation, classification, and meta-analysis to explore alternative treatments for SARS-CoV-2 infections, their interrelationships, and statistical trends in incidence. Results The study identifies diverse alternative therapies for treating SARS-CoV-2 infections, highlighting herbal medicine, acupuncture, reflexology, biohacking, homoeopathy, and magnetotherapy. It underscores the potential benefits of herbal remedies like garlic, ginger, chamomile, and honeysuckle, as well as vitamins (C, D, B12) and minerals (zinc, selenium) in managing COVID-19 symptoms. Conclusion While of-fering holistic benefits, these therapies warrant cautious consideration due to limited scientific backing and potential interactions. Cultural understanding, patient-provider dialogue, and informed choices are key in harnessing the potential of alternative medicine along-side conventional approaches for managing COVID-19 challenges.

Resumo Introdução A relevância do tema estudado reside na comple-xidade do tratamento da infeção causada pelo SARS-CoV-2. Objetivo Discutir as potenciais vantagens e desvantagens dos tratamentos alternativos em comparação com as abordagens médicas convencionais e realçar a importância da comunicação colaborativa entre os doentes e os prestadores de cuidados de saúde na tomada de decisões informadas sobre os tratamentos alternativos do vírus SARS-CoV-2. Métodos A metodologia de investigação utilizou métodos de análise da literatura, incluindo abordagens bibliográficas e bibliosemânticas. O estudo utilizou métodos teóricos, sistemáticos e estatísticos, incluindo análise, síntese, generalização, interpretação, classificação e meta-aná-lise para explorar tratamentos alternativos para as infecções por SARS-CoV-2, suas inter-relações e tendências estatísticas da incidência. Resultados O estudo identifica diversas terapias alternativas para o tratamento das infecções por SARS-CoV-2, destacando a fitoterapia, a acupunctura, a reflexologia, o biohacking, a homeopatia e a magnetoterapia. Sublinha os potenciais benefícios dos remédios à base de plantas como o alho, o gengibre, a camomila e a madressilva, bem como das vitaminas (C, D, B12) e dos minerais (zinco, selénio) na gestão dos sintomas da COVID-19. Conclusão Embora ofereçam benefícios holísticos, estas terapias devem ser consideradas com cautela devido ao apoio científico limitado e às potenciais interações. A compreensão cultural, o diálogo paciente-prove-dor e as escolhas informadas são fundamentais para aproveitar o potencial da medicina alternativa juntamente às abordagens convencionais para gerir os desafios da COVID-19.

Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study.

BACKGROUND: SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. METHODS: A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19-65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. RESULTS: We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85-14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14-14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62-13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. CONCLUSIONS: All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27.

The effect of nutritional biochemical indexes on the hospitalization outcome of COVID-19.

Aims to investigate the relationship between nutritional biochemical indexes and hospitalization outcomes of COVID-19 patients, 132 continuous patients with COVID-19 from December 2022 to January 2023 in Lishui hospital were retrospectively analyzed, and the nutritional biochemical indexes in peripheral blood, such as total protein, albumin, calcium, phosphorus, and magnesium, were detected. Meanwhile, the levels of several cytokines and PBMC subtypes (CD4, CD3, CD8, NK and B cells) were detected too. The Spearman correlation analysis, one-way ANOVA and multivariate logit regression were conducted. Results suggested that the levels of total protein and albumin were significantly decreased in patients with poor outcomes, and the levels of calcium, phosphorus, and magnesium were significantly correlated with hospitalization outcomes. COVID-19 patients with diabetes had higher levels of IL-6 and IFN-γ than those patients without diabetes. The levels of IL-2, IFN-γ, IL-6 and Il-10 in the dead patients were significantly higher than those in the recovery and worse patients. Total protein and albumin were significantly positively correlated with levels of NK and B, CD4, CD8, CD3 lymphocytes. The levels of CD4, CD8 and CD3 lymphocytes were significantly decreased in dead patients than other patients. Multivariate logit regression analysis suggests that lymphocyte number, albumin and IL-6 are independent risk factors to evaluate the hospitalization outcome. In summary, nutritional biochemical indexes were significantly corelated with cytokines and PBMC subsets, and had an impact on the severity of COVID-19 patients. Improvement of low protein malnutrition is broad-spectrum and basic strategy to improve the hospitalization outcome of COVID-19.

COVID-19 prediction using Caviar Squirrel Jellyfish Search Optimization technique in fog-cloud based architecture.

In the pandemic of COVID-19 patients approach to the hospital for prescription, yet due to extreme line up the patient gets treatment after waiting for more than one hour. Generally, wearable devices directly measure the preliminary data of the patient stored in capturing mode. In order to store the data, the hospitals require large storage devices that make the progression of data more complex. To bridge this gap, a potent scheme is established for COVID-19 prediction based fog-cloud named Caviar Squirrel Jellyfish Search Optimization (CSJSO). Here, CSJSO is the amalgamation of CAViar Squirrel Search Algorithm (CSSA) and Jellyfish Search Optimization (JSO), where CSSA is blended by the Conditional Autoregressive Value-at-Risk (CAViar) and Squirrel Search Algorithm (SSA). This architecture comprises the healthcare IoT sensor layer, fog layer and cloud layer. In the healthcare IoT sensor layer, the routing process with the collection of patient health condition data is carried out. On the other hand, in the fog layer COVID-19 detection is performed by employing a Deep Neuro Fuzzy Network (DNFN) trained by the proposed Remora Namib Beetle JSO (RNBJSO). Here, RNBJSO is the combination of Namib Beetle Optimization (NBO), Remora Optimization Algorithm (ROA) and Jellyfish Search optimization (JSO). Finally, in the cloud layer, the detection of COVID-19 employing Deep Long Short Term Memory (Deep LSTM) trained utilizing proposed CSJSO is performed. The evaluation measures utilized for CSJSO_Deep LSTM in database-1, such as Mean Squared Error (MSE) and Root Mean Squared Error (RMSE) observed 0.062 and 0.252 in confirmed cases. The measures employed in database-2 are accuracy, sensitivity and specificity achieved 0.925, 0.928 and 0.925 in K-set.

Predicting perinatal outcomes in women affected by COVID-19: An artificial intelligence (AI) approach.

This study aimed to explore the role of artificial intelligence (AI) in predicting perinatal outcomes among women with COVID-19. Data was collected from hospitals in the Middle Euphrates and Southern regions of Iraq, with 152 pregnant patients included in the study. Patients were categorized into mild and severe infection groups, and their serum samples were analyzed for mineral levels (magnesium, copper, calcium, sodium, potassium, zinc, selenium, and iron) and immune factors (IL-6, IL-8, IL-32, IL-10, IL-18, IL-37, IL-38, IL-36, and IL-1). The findings revealed significant associations between specific mineral levels, immune factors, and perinatal outcomes. Mineral levels such as magnesium (75.5% mild infection, 80.9% severe infection), copper (68.2% mild infection, 64.3% severe infection), calcium ion (81.8% mild infection, 76.2% severe infection), sodium (70.9% mild infection, 69.0% severe infection), potassium (72.7% mild infection, 71.4% severe infection), zinc (61.8% mild infection, 54.8% severe infection), selenium (78.2% mild infection, 82.9% severe infection), and iron (74.5% mild infection, 68.3% severe infection) showed varying percentages associated with mild and severe infections. Immune factors such as IL-6 (32% mild infection, 21% severe infection), IL-8 (15% mild infection, 7% severe infection), IL-32 (24% mild infection, 9% severe infection), IL-10 (7% mild infection, no severe infection), IL-18 (13% mild infection, 11% severe infection) demonstrated varying percentages associated with perinatal outcomes, while other interleukins showed no changes in severe infections. These results highlight the potential of AI in predicting outcomes for pregnant women with COVID-19, which could aid in improving their management and care. Further research and validation of predictive models are recommended to enhance accuracy and applicability.

Bovine colostrum and its potential contributions for treatment and prevention of COVID-19.

Bovine colostrum (BC) is the initial milk an animal produces after giving birth, particularly in the first few days. Numerous bioactive substances found in BC, including proteins, enzymes, growth factors, immunoglobulins, etc., are beneficial to human health. BC has a significant role to play as part of a healthy diet, with well-documented health and nutritional advantages for people. Therefore, the use of BC and its crucial derivatives in the development of functional food and pharmaceuticals for the prevention of several diseases such as gastrointestinal and respiratory system disorders is becoming increasingly popular around the world. A novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of a cluster of pneumonia cases that is called Coronavirus Disease 2019 (COVID-19) in China. After the first SARS-CoV-2 virus-related fatality was announced, the illness quickly spread throughout China and to other continents, causing a pandemic. Since then, numerous studies have been initiated to develop safe and efficient treatments. To prevent viral infection and potential lingering effects, it is important to investigate alternative treatments for COVID-19. Due to its effective bioactive profile and its immunomodulatory roles in biological processes, BC might be considered a promising approach to assist in combating people affected by the SARS-CoV-2 or prevention from the virus. BC has immunomodulatory effects because to its high concentration of bioactive components such as immunoglobulins, lactoferrin, cytokines, and growth factors, etc., which might help control immunological responses, potentially fostering a balanced immune response. Furthermore, its bioactive components have a potential cross-reactivity against SARS-CoV-2, aiding in virus neutralization and its comprehensive food profile also supplies important vitamins, minerals, and amino acids, fostering a healthy immune system. Hence, the possible contributions of BC to the management of COVID-19 were reviewed in this article based on the most recent research on the subject. Additionally, the key BC components that influence immune system modulation were evaluated. These components may serve as potential mediators or therapeutic advantages in COVID-19.

Randomised controlled trial to compare efficacy of standard care alone and in combination with homoeopathic treatment of moderate/severe COVID-19 cases.

BACKGROUND & OBJECTIVES: No definite treatment is known for COVID-19 till date. The objective of this study is to assess the efficacy of customized Homoeopathic medicines, when used as an add-on treatment to Standard of Care (SOC), in patients suffering from moderate to severe COVID-19 infection. METHODS: This was a randomized, controlled, single-blind, parallel-group trial where 214 COVID19-positive patients were screened for moderate and severe cases of COVID-19. Adjuvant homoeopathic medicines were given in the treatment group and SOC was given to both groups. The duration of oxygen support was compared as the primary outcome. Subjects were followed for 28 days or till the end-point of mechanical ventilation/ death. RESULTS: Of 129 subjects included, 57 and 55 were severe; and 8 and 9 were moderate cases in Homoeopathy and SOC arms, respectively. In all, 9 (15.2%) participants in Homoeopathy and 20 (32.2%) participants in SOC arms eventually expired (p<0.05). Oxygen support was required for 9.84±7.00 and 14.92±7.549 days in Homoeopathy and SOC arms, respectively (p<0.005). Subjects receiving Homoeopathy (12.9±6.days) had a shorter hospitalization stay than in SOC (14.9±7.5 days). Homoeopathy arm (10.6±5.7 days) also showed statistically significant mean conversion time of of Realtime-Polymerase Chain Reaction (RT-PCR) from positive to negative than the SOC arm (12.9±5.6 days). The mean score of Clinical Outcome Ordinal Scale (COOS) was lower in the Homoeopathy arm. Laboratory markers [Interleukins (IL)-6, C-reactive protein (CRP), Neutrophils-Lymphocytes ratio (NLR)]were normalized earlier in Homoeopathy arm. CONCLUSION: Homoeopathy, as add-on therapy with SOC for COVID-19 management, demonstrates a reduction in mortality and morbidity, by reduced requirement of oxygen and hospitalization. Some laboratory markers are normalized at an earlier time. Hence, there is overall control over the disease. Registry: The study was registered on the http://ctri.nic.in/Clinicaltrials website under identifier number: CTRI/2020/12/029668 on 9th December 2020.

Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: In the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated. METHODS: Laboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day. RESULTS: The results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p < 0.05). In addition, the patients in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in TNF-α level in the treatment group, while a 31% increase in this cytokine level in the placebo was observed (p > 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved. CONCLUSIONS: In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS. TRIAL REGISTRATION: Iranian Registry of Clinical Trials RCT20170731035423N2 . Registered on June 12, 2020.