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Potential Interventions for Novel Coronavirus in China: A Systemic Review
Abstract
An outbreak of a novel coronavirus (COVID‐19 or 2019‐CoV) infection has posed significant threats to international health and the economy. In the absence of treatment for this virus, there is an urgent need to find alternative methods to control the spread of disease. Here, we have conducted an online search for all treatment options related to coronavirus infections as well as some RNA virus infection and we have found that general treatments, coronavirus‐specific treatments, and antiviral treatments should be useful in fighting COVID‐19. We suggest that the nutritional status of each infected patient should be evaluated before the administration of general treatments and the current children's RNA virus vaccines including influenza vaccine should be immunized for uninfected people and health care workers. In addition, convalescent plasma should be given to COVID‐19 patients if it is available. In conclusion, we suggest that all the potential interventions be implemented to control the emerging COVID‐19 if the infection is uncontrollable. This article is protected by copyright. All rights reserved.
... La presencia de fiebre incrementa el gasto energético basal: por cada grado arriba de 37 o C, el GEB se multiplica por 1.13, es decir, un aumento del 13% del gasto energético basal (62). Este aumento en energía también se traducirá en un aumento del requerimiento de líquidos, por lo que se debe recomendar un consumo de al menos 1 mL de agua/Kcal (21). Se sugiere considerar el agua como fuente principal hídrica, aunque también pueden incluirse caldos vegetales, infusiones, té, gelatinas o frutas. ...
... Las potenciales intervenciones nutrimentales ante COVID-19 se centran en: vitaminas A, D, E, C, vitaminas del complejo B, ácidos grasos poliinsaturados omega-3, selenio, zinc y hierro (21). Sin embargo, se requiere de mucha investigación todavía para poder establecer dosis y tiempos de suplementación efectivos contra SARS-CoV-2. ...
... La disminución de la vitamina D en personas con obesidad es un hallazgo constante, esta vitamina, además de su papel en el mantenimiento de la integridad ósea, también estimula la maduración de diversas células, incluidas las células inmunes, así mismo se ha encontrado que la corrección del déficit de vitamina D tiene un efecto favorable sobre la masa muscular y el efecto mecánico de la depleción de la musculatura torácica puede aumentar el riesgo de mortalidad en estos pacientes. Otro elemento a considerar es el aporte ácidos grasos poliinsaturados de cadena larga (AGPI) los cuales son mediadores importantes de inflamación y la respuesta inmune adaptativa (21,(109)(110)(111). ...
... Microfluidic instruments are used as a platform for biological and chemical analyses and as a tool at higher laboratory levels that require solutions or fluids for sample preparation or quantification. All these features are due to the micrometric scale of fluidic components of microfluidic systems, which increases the capability or efficiency of analyzer systems and provides more accuracy in quantitative biological measurements [129]. ...
... The high power of microfluidic systems can have many functional advantages in molecular diagnosis, such as optimizing or reducing the time of research studies and reducing consumption costs by increasing the number of reactions that are integrated simultaneously on a microchip and automatically. In other words, the scale of performing the reaction at the bench-top level can be an important principle and an obstacle to the analysis and review of the results and different analyses, and microfluidic systems provide the collection and access of inaccessible information [129][130][131]. ...
... The small design and format of microfluidic systems, which are made using biocompatible types, have made this technology compatible with many optical diagnostic methods, including microscopic pho-tography and spectroscopy. A microfluidic system is not the end of research; however, these tools are viewed as a starting point for research in the field of diagnosis [129][130][131][132][133]. ...
Considering the importance of early diagnosis of diseases as a challenge in medicine, which can be significantly effective in increasing the health level of society via preventing the progress and spread of infectious diseases, especially in developing and underprivileged countries with insufficient medical facilities. On the other hand, medical diagnosis methods that require advanced equipment and tools with expert staff limit the use of these tests. Along with the continuous development of technology, microfluidic systems have shown great potential to advance biomedical research that was previously unattainable using conventional techniques. For point-of-care applications, these systems can quickly detect diseases at low cost. This study discusses the challenges in the field of medical diagnosis and the importance of microfluidic systems as the best candidate to answer this need. Also, it describes the components of the microfluidic system, their manufacturing methods, and some of their most important applications in the field of health.
... We performed PCM using Pharma Gist, an internet web server [17]. The researchers first drew the 2D structures of these four compounds using ChemSketch and then saved them in the mol2 format using Open Babel software [18]. Pharma Gist was then used to import all these compounds and generate their common 3D properties. ...
... A set of 10 compounds with a root mean square deviation (RMSD) of less than 0.57 were selected for additional research from many hits. While designing a second batch of ten compounds [11][12][13][14][15][16][17][18][19][20], we considered the pharmacophoric characteristics of both the standards and the compounds retrieved from the zinc database. All the 20 compounds thus obtained were docked against Mpro of SARS-CoV-2, owing to their importance in the present research. ...
... Compound 16 exhibits several infractions of both criteria for drug-like qualities, but compound 17, which had a value of less than 90 and was CNS vulnerable, was unable to maintain the momentum. Compounds 1,10,11,12,14,18, and 20 are among the other compounds that must overcome a similar challenge. All of these compounds had protease affinities that were within the acceptable range of -7.0 to -7.7 Kcal/ mol. ...
... Berdasarkan hasil penelitian (Mahmoodpoor dkk, 2021) pemberian vitamin C dengan dosis yang relatif tinggi secara intravena kepada pasien sakit kritis menderita pneumonia berat adalah aman serta dapat mengurangi peradangan, mengurangi lama waktu penggunaan ventilasi serta penggunaan vasopressor tanpa efek signifikan terhadap kematian. Berdasarkan (Zhang & Liu, 2020) vitamin B dapat membantu mengurangi peradangan dan dapat mengurangi lama rawat inap atau waktu kejadian penyakit pernafasan dalam jangka waktu yang lama. Hasil penelitian (Noviyanti, 2022) menunjukkan tidak terdapat hubungan antara lama penggunaan ventilator mekanik yang lama dengan adanya kejadian kematian di Intensive Care Unit (ICU) di RSUD Dr. H. Abdul Moeloek. ...
... Hasil uji Log-Rank pada faktor pemberian vitamin B kompleks menghasilkan nilai p sebesar 0,623 karena nilai p (0,623) > α (0,05) oleh karena itu, tidak ada perbedaan waktu ketahanan hidup pasien pneumonia antara pasien yang tidak diberikan vitamin B kompleks dengan diberikan vitamin B kompleks sehingga faktor pemberian vitamin B kompleks tidak memiliki hubungan signifikan terhadap ketahanan hidup pasien pneumonia di RSUD Aceh Tamiang tahun 2022. Berbeda dengan penelitian (Zhang & Liu, 2020) vitamin B dapat membantu mengurangi peradangan, memperkuat fungsi pernafasan, menjaga homogenitas endotel, menghambat hiperkoagulasi, mengaktifkan respon imun bawaan dan adaptif dengan baik serta dapat mengurangi rawat inap atau waktu kejadian penyakit pernafasan dalam jangka waktu yang lama. 66 TROPHICO: Tropical Public Health Journal Vol.04, No.02 (2024) [59][60][61][62][63][64][65][66][67][68] 4.6. ...
Globally, pneumonia is the fourth leading cause of death in the world and the deadliest infectious disease. The 2019 Global Burden of Disease (GDB) study stated that lower respiratory tract infections were responsible for more than 2.49 million deaths with the highest mortality rate in patients over 70 years of age at 1.23 million and 672,000 deaths in patients less than 5 years old. With an increase in cases and high mortality rates in pneumonia, it is necessary to analyze the survival of pneumonia patients by conducting a survival analysis. The design of this study was a retrospective cohort study that observed pneumonia patients who had been hospitalized by looking for factors associated with pneumonia mortality. The population in this study was 1,371 with a sample size of 363 patients. The results of the research factor of vitamin C p-value (0.173) > (0.05) there is no relationship of vitamin C. The factor of ventilator p-value (0.001) < (0.05), there is a relationship between ventilator and pneumonia survival with HR = 1451.802. The factor of decreased consciousness p-value (<0.0001) < (0.05) there is a relationship between decreased consciousness and pneumonia survival with HR = 3.923. The severity factor p-value (0.011) < α (0.05), there is an association of severity with the survival of pneumonia with HR = 3739.9. The author suggests that medical personnel prioritize patients using ventilators and their severity to prevent death and provide optimal care on day 12 because it has a high failure rate. Keywords: Survival. Pneumonia, Cox regression
... Therefore, the importance of knowledge related to Covid-19 and nutrition to increase body immunity needs to be adequately advocated. Many studies have been carried out in several countries, such as Bangladesh, Sudan, the United States, and China, related to knowledge, attitude, and behavior towards Covid-19 8,[14][15][16] . Most of these studies explore knowledge, attitudes, and attitudes regarding basic information about the coronavirus, the spread of the virus, social distancing, and measures taken to prevent the spread of infection. ...
... This study found that most of the sample were public health students who tended to have good knowledge regarding nutrition to increase immunity (75%), so it becomes an advantage in this study where the related samples are students who already have more or less good knowledge because of their high intellectual level. However, in terms of implementing eating habits from the knowledge they have, of course, it will be different for each student 16 . Not only knowledge some factors can influence a person's eating habits, such as food preferences, economic, social, and cultural factors, religion, as well as education or health awareness 17 . ...
Latar Belakang: Penyebaran covid-19 di Indonesia menyebabkan banyaknya kasus kematian. Untuk menangani covid-19 salah satunya yaitu meningkatkan imunitas. Pemuda merupakan golongan penduduk mayoritas di dunia yang artinya banyak berpotensi terpapar virus corona. Pemuda termasuk diantaranya mahasiswa cenderung mudah terpapar virus corona karena memiliki kebiasaan makan yang tidak baik (kurangnya asupan protein, vitamin c dan vitamin a). Kebiasaan makan yang tidak baik dapat terjadi karena minimnya pengetahuan terkait gizi utamanya yang berhubungan dengan upaya peningkatan imunitas. Tujuan: Mengetahui hubungan pengetahuan terkait gizi dalam upaya peningkatan imunitas tubuh dengan kebiasaan makan makanan sumber protein, vitamin A dan vitamin C selama pandemi covid-19 pada mahasiswa Universitas Airlangga. Metode: Metode kuantitatif deskriptif dengan menggunakan desain penelitian cross-sectional dengan sampel mahasiswa Universitas Airlangga. Data didapatkan menggunakan survei online dengan menggunakan metode acciedental sampling, Selanjutnya Peneliti menyebarkan kuisioner online berupa google formulir dengan bantuan media berupa pamflet melalui media sosial. kemudian data dianalisis menggunakan uji Chi-square. Hasil: Sebagian besar responden merupakan mahasiswa Fakultas Kesehatan Masyarakat, memiliki jenis kelamin perempuan, berusia 21 tahun, dan tinggal bersama keluarga inti di rumah selama pandemi Covid-19, memiliki pengetahuan yang baik terkait Gizi dalam upaya meningkatkan imunitas (75%), kecuali factor yang dapat menurunkan imunitas. Terdapat hubungan positif yang signifikan antara pengetahuan dengan kebiasaan makan. Kesimpulan: Terdapat hubungan yang signifikan antara pengetahuan terkait gizi untuk meningkatkan imunitas pada pandemi covid-19 melalui kebiasaan makan makanan sumber protein, vitamin A, dan vitamin C
... It can inhibit viral invasion to the cells by using endosome pathway. They have been used in treating patient with Zika virus [11] and Borna virus disease. [12] These viruses use acidic endosome for activating and entering inside host cells and by preventing the acidification of endosome these drugs inhibit entry of virus inside host cells. ...
Coronavirus is a family of RNA viruses that come from the genus beta coronavirus, this virus is distributed in many species like, birds, humans and other mammals. Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. In most infected people with COVID-19 virus, the symptoms will appear as mild to moderate respiratory, symptoms and most of them can recover without needing specific treatment. On the other hand, older people and those with fundamental medical, problems such as, cardiovascular disease, diabetes, chronic respiratory disease and cancer are more likely to develop a serious illness and require special care and treatment.
... [6] In the past, the Passive Immunotherapy (PIT) has been used as a possible treatment option when no proven drugs or specific vaccine was available for the emerging infections. [7,8] It has been used as an empirical therapy during the Ebola virus outbreak in 2014, and a treatment protocol of MERS-CoV with convalescent therapy was developed in 2015. [9] This therapeutic approach with convalescent plasma (CP) for other viral infections such as H1N1 influenza, H5N1 avian influenza and SARS-CoV has also suggested ULJRI Convalescent Plasma Therapy in Coronavirus Disease 2019 (COVID-19) Patients: A Brief Review that the transfusion of CP had good results. ...
The recent outbreak of the COVID-19 pandemic has reevaluated effectiveness of the convalescent plasma therapy (CPT). This review was carried out to assess the usefulness of CPT in critically COVID-19 patients, based on the published data to date. To the best of our knowledge, this is the second review of the usefulness of CPT in COVID-19 patients. PubMed, Google Scholar, Medline and EMBASE databases were searched for the relevant reports up to June 21, 2020. All the records of the published data were analyzed according to eligibility criteria protocols. Five different studies on CPT for COVID-19 critically ill patients were included in this review. The significant findings from the records are: (a) the CPT may help to reduce mortality in the seriously ill patients (b) administration of CPT increased antibodies titer and reduced the level of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA beyond detection limit (c) transfusion of convalescent plasma (CP) subsided clinical symptoms. Based on the currently available data, the CPT in the COVID-19 patients seems effective, safe and reduces mortality. There is urgent need of performing well-designed, multicenter clinical trials for establishing efficacy of the CPT in COVID-19 patients.
... A falta de tratamentos farmacológicos para a Covid-19 impulsionou o consumo global de suplementos dietéticos, especialmente para fortalecimento da imunidade [11] . Esses suplementos, que complementam a dieta com nutrientes, substâncias bioativas ou probióticos, ganharam destaque no mercado [12,13] . ...
... É importante destacar que os pa-cientes críticos podem apresentar hipercatabolismo com consequente redução da massa muscular esquelética. Além disso, a ingestão proteica tem sido relacionada como fator determinante para uma satisfatória evolução nutricional e prognóstico clínico dos pacientes críticos com COVID-19 23 . ...
INTRODUÇÃO: O Corona Virus Disease (COVID-19) é uma infecção de elevada transmissibilidade e está associada com maior suscetibilidade ao desenvolvimento de desnutrição. Desta forma, a terapia nutricional enteral deve estar integrada ao tratamento global deste agravo. OBJETIVO: Analisar os fatores clínicos, nutricionais e bioquímicos associados ao desfecho clínico de pacientes com COVID-19 internados em uma Unidade de Terapia Intensiva (UTI). MÉTODOS: Trata-se de uma série de casos, realizado no período de março a julho de 2020, com os dados registrados nas fichas de acompanhamento nutricional dos pacientes internados com COVID-19. As variáveis analisadas foram: demográficas (idade e sexo); clínicas (comorbidades, doença de base e desfecho), antropométricas, bioquímicas e de suporte nutricional. RESULTADOS: A amostra foi composta por 102 pacientes, 65,7% apresentaram síndrome respiratória aguda grave, a principal doença de base observada foi as doenças cardíacas (23,5%) e 69,3% dos pacientes evoluíram para a alta da UTI. Com relação às variáveis nutricionais, aproximadamente 50% dos pacientes receberam alimentação por via enteral e 73,3% iniciaram de forma precoce. No que se refere aos marcadores bioquímicos, os pacientes que foram a óbito, apresentaram maiores valores das razões proteína C reativa (PCR) /albumina (p=0,024) e das concentrações de PCR (p=0,012) quando comparado com os que evoluíram para alta da UTI. Além disso, observa-se que os idosos (HR ajustada =3,62; IC95% 1,19 – 10,97) e o início precoce da terapia nutricional enteral (HR ajustada = 10,62; IC95% 2,41 – 46,87) foram fatores relacionados com a alta da UTI. CONCLUSÃO: O acompanhamento do processo inflamatório através de diferentes marcadores parece ser um bom parâmetro de evolução clínica desses pacientes. Além disso, os benefícios da terapia de nutrição enteral precoce podem estar associados à melhor evolução clínica e redução de complicações durante internamento.
... Explorations revealed that decent nourishment sponsors the insusceptible framework and has imperative significance on the framework. 3 Sustenance affects body opposition and microorganisms. Inordinate strain, traumas, ambustions, etc., could cause protein obliteration, thereby diminishing body opposition. ...
Balanced and healthy nutrition is a vital to attain a good immune response. Numerous studies have reported that boosting up adaptive immunity through nutritional interventions can impede viral infections. With the present leading challenge of the COVID-19 pandemic globally, maintaining good nourishment is indispensable to remain immune against the novel virus. By and large, ineffectively fed people are at a higher risk of creating different kinds of contaminations. In addition, constant and extreme contagion can cause health problems and demolish a patient’s nourishing status, making them susceptible to different diseases. During the COVID-19 pandemic, everyone must screen their eating routine and nourishing status. Good nutrition can subside the ongoing unprecedented health complications and deaths. Evaluating the clinical status of COVID-19 cases at the hour of clinic confirmation is strongly recommended. Specific dietary help is prescribed to be given to those in the high-hazard bunch, asymptomatic transporters, and patients with moderate or extreme COVID infection. An assortment of micronutrients techniques to treat COVID-19 can prove beneficial at the preliminary stage of the clinical attendance. The prompt supplementation of specific supplements in gentle cases can forestall the movement of sicknesses.
... Consequently, SARS-CoV-2 shares 80% of its genome with SARS-CoV (9,10). Considering that COVID-19 has recently become a pandemic disease (11) and no specific treatment has ever been found for it, finding the right solution to prevent and control its spread is of great necessity. Factors that increase the risk of COVID-19 and death include age (risk of death is higher in the elderly), gender (prevalence and mortality rates are higher among men), high blood pressure, chronic metabolic diseases such as diabetes, chronic lung diseases such as asthma, coronary artery disease, congestive heart failure, kidney disease, any conditions that suppress immunity, gastrointestinal/liver disease, and blood disorders. ...
Introduction: Given the high spread and mortality rate of COVID-19, it is of great importance to find solutions to prevent it. In this study, the role of physical activity and body mass index in the development or prevention of COVID-19 was investigated.
Materials and methods: In this cross-sectional study, participants included 155 patients with coronavirus selected as the experimental group and 150 age-matched healthy people included in the control group. The participants' physical activity levels were assessed using Beck's physical activity questionnaire. Independent t-test and binary logistic regression were run to analyze the data. Results: The findings showed a significant difference between the patient and control groups body mass index (BMI), and total physical activity (P< 0.05). On the other hand, total physical activity had a significant effect on COVID-19 prevention (P< 0.05), but BMI had a significant increasing effect on the risk of COVID-19 (P< 0.05).
Conclusion: It seems that physical activity can be effective in the prevention of COVID-19, but a higher body mass index may increase the risk for the development of COVID-19.
... Patient safety and optimal health outcomes are a priority. Interactions could either increase (synergy) or decrease (antagonism) the potency of conventional antimicrobials (Zhang and Lui, 2020). ...
... changes the T-cell differentiation profile in both the CD4 + and CD8 + subsets of PASC) (Minutolo et al. 2023). According to some authors, administration of Tα 1 to patients prior to corticosteroid treatment may protect lymphocytes from the immunocytotoxic effects of these drugs (Zhang and Liu 2020;Artym and Zimecki 2021). ...
Background
The thymus is the main lymphoid organ that regulates the functions of the immune system, protecting against pathogens, tumors, antigens, and mediators of tissue damage. It produces a family of hormone-like peptides that can modulate physiological processes such as stimulation or suppression of immune responses, angiogenesis, and wound healing.
Objective
This review aims to comprehensively characterize the properties of thymic peptides and their clinical applications.
Methodology
This article discusses the structure, biological properties, mechanism of action, and therapeutic applications of the most important thymic hormones (thymosin alpha 1, thymosin beta-4, thymulin, and thymopoietin), as well as preparations that are purified thymic extracts.
Results
Thymic peptides and extracts act in multiple manners on the immune system: they stimulate the differentiation and maturation of T cells, regulate the activity of natural killer cells and dendritic cells, and induce the release of proinflammatory cytokines, and their immunomodulatory effects have been confirmed in numerous clinical studies. An important feature of thymus preparations is their therapeutic safety—even long-term use does not cause side effects.
Conclusions
A wide range of therapeutic uses, i.e., from defensive and immunomodulatory tasks to participation in tissue regeneration processes, has led to the use of thymic peptides in the treatment of neoplastic diseases, viral infections, autoimmune diseases or immunodeficiencies. Further investigation of the mechanisms of action of thymic peptides may contribute to the discovery of new therapeutic targets.
... Identification of 25 genes responsible for selenoprotein biosynthesis in the human body provides the basis of the significance of human Se status optimization. Indeed, the protective role of numerous selenoproteins against viral diseases [1,2], including COVID-19 [3,4], cardiovascular diseases, and cancer [5][6][7], makes selenium one of the most promising elements to improve human health via optimization of the human antioxidant status [8]. ...
Allium species have great potential in the production of functional food via selenium biofortification. This review is devoted to the specificity of Allium plant biofortification with Se, including the genetic peculiarities, effect of the chemical form of the microelement, methods of supply, sulfur and AMF effects, and hormonal regulation. The biosynthesis of methylated Se amino acids and the beneficial effect of Se treatment on secondary metabolite accumulation and plant yield are discussed. Special attention is paid to the production of functional foods based on Allium plants enriched in different ways: bread with leek leaf powder, Allium microgreens and seedlings, and ‘Black garlic’ biofortified with Se. Further focus is provided to the high variability of Allium crop yield and quality under Se supply governed by genetic factors and environmental stresses, and to the need for plant growth technology optimization to obtain the predicted nutritional characteristics of the derived functional product with high anti-carcinogenic activity.
... A review on Coronaviruses emphasize on supportive treatment with various vitamins such as vitamin A,B,C,D and E as they strengthen the immune system. Lacking vitamin B and D have been shown to decrease the efficiency of immune system and cause chronic illnesses, including respiratory illness 53 . ...
... Since chymotrypsin-like and papain-like proteases are essential coronaviral encoded proteins responsible for both replications of the virus and inhibition of host immune response, targeting these proteases are therefore quite attractive measures in the treatment and prevention of coronaviral diseases (Zhang and Liu, 2020). Interestingly, some flavonoids have already been demonstrated to have inhibitory effects against these proteases Ryu et al., 2010;Jo et al., 2019;Mouffouk et al., 2021). ...
Notably, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19) have all had significant negative impact on global health and economy. COVID-19 alone, has resulted to millions of deaths with new cases and mortality still being reported in its various waves. The development and use of vaccines have not stopped the transmission of SARS coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, even among vaccinated individuals. The use of vaccines and curative drugs should be supplemented with adoption of simple hygiene preventive measures in the fight against the spread of the virus, especially for healthcare workers. Several virucidal topical antiseptics, such as povidone-iodine (PVP-I), citrox, cyclodextrins among others, have been demonstrated to be efficacious in the inactivation of SARS-CoV-2 and other coronaviruses in both in vitro and in vivo studies. The strategic application of these virucidal formulations could provide the additional impetus needed to effectively control the spread of the virus. We have here presented a simple dimension towards curtailing the dissemination of COVID-19, and other coronaviruses, through the application of effective oral, nasal and eye antiseptics among patients and medical personnel. We have further discussed the mechanism of action of some of these commonly available virucidal solutions while also highlighting some essential controversies in their use.
... Thus, the use of CP is a possible therapy in patients whose condition exposes them to a risk of early death due to COVID-19 32,33 . CP has characteristics such as having polyclonal antibodies and being easy and quick to obtain, which make it potentially useful in adverse scenarios, such as the context of emerging variants of SARS-CoV-2. ...
Methods:
We designed a quasi-experimental study that included 156 patients with SARS-CoV-2 infection confirmed by RT-qPCR and severe symptoms who received CP. As a control group, we selected a historical cohort of 113 individuals admitted with COVID-19 and severe symptomatology before the starting date of the study. Clinical status and mortality during the study period were recorded.
Results:
There were no adverse reactions to CP administration. In the CP group, days on mechanical ventilation were significantly lower than the control group (2.8±5.08 days vs. 4.7±6.19 days; p= 0.0081). Moreover, a significant difference was observed in the number of days stayed in the critical patient unit (CPU) in CP vs. controls (4.2±5.47 vs. 5.8±6.39 days, p= 0.0281).
Conclusions:
We observed no association between CP administration and survival at 14 days. Treatment with CP was safe and not associated with adverse events. In addition, using CP was associated with a reduction in both stay at the CPU and connection to mechanical ventilation.
... Inhaled NO is well documented to improve oxygenation in a variety of pathological conditions [169,170]. The use of inhaled NO has been popular during pediatric and adult cardiac surgeries and lung and heart transplantations [171]. ...
Nitric oxide (NO) is a key signaling molecule involved in numerous physiological and pathological processes within the human body. This review specifically examines the involvement of NO in age-related diseases, focusing on the cardiovascular, nervous, and immune systems. The discussion delves into the mechanisms of NO signaling in these diseases, emphasizing the post-translational modifications of involved proteins, such as S-nitrosation and nitration. The review also covers the dual nature of NO, highlighting both its protective and harmful effects, determined by concentration, location, and timing. Additionally, potential therapies that modulate NO signaling, including the use of NO donors and nitric oxide synthases (NOSs) inhibitors in the treatment of cardiovascular, neurodegenerative, and oncological diseases, are analyzed. Particular attention is paid to the methods for the determination of NO and its derivatives in the context of illness diagnosis and monitoring. The review underscores the complexity and dual role of NO in maintaining cellular balance and suggests areas for future research in developing new therapeutic strategies.
... COVID-19 infection is a recently emerging respiratory disease initiated by the highly contagious and severe acute respiratory SARS-CoV-2 with uncontrolled inflammatory cytokine-storm feature that spread globally in 2019-2023 [29,30]. The inhalation of SARS-CoV-2 contaminated respiratory droplets and subsequent infection of the respiratory system, the alveolar epithelial cells, and vascular endothelial cells elicit macrophages, monocytes, and lymphocytes in the inflammatory responses of the affected cells [10,31]. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections tend to cause severe symptoms in individuals with certain pre-existing conditions, such as advanced age, comorbidities, and being male. Studies have shown direct correlations between these factors and infection severity. Other factors like inflammation and oxidative stress and their concomitant cytokine expressions further complicate disease severity. Severity in elderly persons is not only helped by age-related inflammatory conditions but exacerbated by a lack of certain immune-boosting nutrients. Retrospective research often focuses on single-nutrient interventions, while this review emphasizes multi-nutrient strategies. Particular emphasis is placed on the synergistic effects of multiple nutrients such as Vitamin D, Zinc, Selenium (Se), Omega-3 PUFAs, probiotics, dietary flavonoids, and peptides in ameliorating the dual inflammation and oxidative stress pathways, especially in high-risk groups like elderly persons. The primary mechanism by which these nutrients exert their effect is the modulation of the virus' replication through interference with the RNA export machinery, among other potential pathways. Quantitative data supports the review's conclusions, with studies showing that 85 % of severe COVID-19 cases are linked to Vitamin D deficiency, while Se's supplementation reduces viral replication by 20 %. Therefore, when aging is a risk factor for an infection, consuming health-promoting diets and healthy lifestyles are good tips, especially for elderly persons. Future research should explore the long-term effects of nutritional interventions, particularly how multi-nutrient approaches can assist in managing post-COVID syndromes, as supported by studies on Omega-3 PUFAs and their ability to reduce cytokine levels by 30 %.
... They play a vital role in various human metabolic reactions, as elicited in Figure 1. For example, vitamins A, C, and D are necessary for immune-boosting body growth and repair activities (Galanakis, 2020;Mohapatra, Mahal, et al., 2023;Zhang & Liu, 2020). Nutraceutical action on viral infection involves several complex mechanisms, including minimizing immune system pathogen-caused damage, initiating the immune function against the pathogen, lowering oxidative damage, activating the immune system against the pathogen, increasing proliferation, including differentiation of regulatory T cells, and modifying and producing proinflammatory cytokines. ...
Nutraceuticals are dietary supplements produced from food sources that are intended to improve health through immune system modulation or by helping to prevent and treat a variety of ailments. Their anti‐inflammatory, immunomodulatory, and antioxidant qualities are well recognized. In certain instances, they even show direct microbiological efficacy against viral infections. Because of their special capacity, they may be able to help slow the spread and effects of very infectious illnesses, such as pandemics like COVID‐19. Nutraceuticals work well against viral infections because of a number of intricate processes. Reducing the harm that infections do to the immune system is one of the main effects. Nutraceuticals have the power to stimulate and activate the immune system, improving the body's capacity to identify and eliminate infections. Additionally, they are essential in reducing oxidative damage, which can result in serious consequences and is frequently intensified during viral infections. Nutraceuticals also strengthen immunity by promoting regulatory T cell differentiation and proliferation, which is crucial for preserving immune system homeostasis and limiting hyperinflammatory reactions. They control the production of proinflammatory cytokines, which helps to avoid cytokine storms during viral infections that may seriously harm tissue. This regulation lowers the danger of hyperinflammation and enhances overall results by supporting a balanced immune response. Through a number of biochemical mechanisms, nutraceuticals can strengthen the body's defenses against viral infections. They promote a more effective and efficient immune response by regulating immune cell activities, oxidative stress reduction, and antioxidant pathway activation. Furthermore, by interacting with different cellular signaling pathways, nutraceuticals can affect the synthesis and function of important immune components. This study clarifies the molecular processes behind the immunomodulatory effects of nutraceuticals, highlighting their crucial role in both treating and preventing viral infections.
... They play a vital role in various human metabolic reactions, as elicited in Figure 1. For example, vitamins A, C, and D are necessary for immune-boosting body growth and repair activities (Galanakis, 2020;Mohapatra, Mahal, et al., 2023;Zhang & Liu, 2020). Nutraceutical action on viral infection involves several complex mechanisms, including minimizing immune system pathogen-caused damage, initiating the immune function against the pathogen, lowering oxidative damage, activating the immune system against the pathogen, increasing proliferation, including differentiation of regulatory T cells, and modifying and producing proinflammatory cytokines. ...
... Coronavirus is a broad type of virus that may cause illness in animals and humans [13]. A number of coronaviruses cause respiratory illnesses in humans, ranging in severity from the common cold to more serious illnesses such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) [14]. ...
The spread of coronavirus (COVID-19) and the need to confront it raises the question about the possibility of reaching a balance between combating this virus, on the one hand, and protecting rights and freedoms, on the other hand. Using a descriptive and analytical approach, the study aimed to answer this question based on international standards and then applied these standards to the reality of the situation in Jordan to determine the extent of the Jordanian government's commitment to human rights standards in the measures taken to combat the coronavirus. It was found that international standards allow for the restriction of rights and freedoms to the extent necessary to maintain health threatened by the Corona virus, however, it is not permissible to expand these restrictions under the pretext of preventing this virus. The study also concluded that the Jordanian government authorities used the Defense Law of 1992, as a law for states of emergency, to restrict freedom of expression without justification. In addition, the closure of schools affected the right to education because the government did not develop a suitable alternative to continue education in schools and universities. On the other hand, the government did not consider the negative economic effects on individuals that caused many individuals to be deprived of their source of livelihood.
... COVID-19, a novel coronavirus, is a member of the largest coronavirus family, Nidovirales (Banerjee et al., 2019;Zhang and Liu, 2020). It is one of the diseases that is transmitted by personal contact. ...
The world was severely hit by the novel coronavirus (COVID-19) in the latter part of 2019. The coronavirus is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) and was first identified in Wuhan, China. The pandemic has devastated every sector of Ghana's economy and has significantly affected the living standards of people in the country. This study seeks to investigate the effects of COVID-19 on the living standards of households in Ghana using the North East Region as a case study. A sample of 399 respondents was drawn from the six (6) districts/municipalities using a single-stage cluster sampling technique. A linear mixed-effects model was used to investigate the fixed effects and the random effects in the study. Results from the study showed that variables such as the marital status of respondents, highest educational level of respondents, dependents, and employment status of respondents had significant fixed effects on the living standard of households in the Region. Overall, the study results showed that COVID-19 had significantly affected most households which has resulted in deteriorating living standards making the overall living standards worse in the Region. It was recommended in the study that a similar investigation be carried out in other parts of the country to get a more holistic view of the effects of the pandemic.
... Vitamin A helps regulate the immune system and protects against infection by maintaining the health of tissues. Carrots, broccoli, red bell peppers, and sweet potatoes are rich sources of vitamin A [21]. Vitamin A deficiency has been associated with increased susceptibility to infections, particularly in the respiratory and gastrointestinal tracts [22]. ...
This review aims to focus on plant-based foods that improve immunity against COVID-19 in all age groups. The World Health Organization (WHO) has declared COVID-19 a global pandemic, and thousands of infections and deaths are being reported every day. This article reviews the properties of bioactive ingredients in foods and herbs to support the human immune system. Many traditional foods can boost immunity along with some antiviral effects. Using lots of vitamins C, D and E and bioactive ingredients like turmeric, ginger, cinnamon, garlic, neem, amla and probiotic yogurt, as well as minerals like zinc and magnesium, these foods can boost the immune response against COVID-19. In addition, certain dietary patterns, such as the Mediterranean diet, have been associated with improved immune function and reduced inflammation. In conclusion, a nutrient-rich diet featuring herbal products and specific vitamins and minerals plays a key role in improving the immune response against COVID-19
... Magnesium helps in strengthening immune cells such as natural killer cells and lymphocytes 190 . Zinc has been shown to have antiviral effects against nCov 191 . It enhances the response of both IgM and IgG antibodies. ...
The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) posed a serious threat to human health worldwide. The death toll was immense in many countries, irrespective of their advanced healthcare system. Post-COVID complications are equally challenging. It was realized that a single method to manage the COVID-19 pandemic and related outbreaks is not adequate; rather, an integrated approach which includes spreading awareness and educating masses about the disease, development of antiviral drugs and other safer drugs for symptomatic treatment of the disease, and mass vaccination is needed to manage such pandemic. Plants used in traditional medicine systems contain diverse secondary metabolites. These have been screened against SARS-CoV-2 and have shown effective antiviral activities. Many of the plant products are also useful for symptomatic treatment. The immune-boosting properties of many phytochemicals have been well documented. In this review, the potential of traditional medicinal plants for effective management of the COVID-19 pandemic is presented.
... Magnesium helps in strengthening immune cells such as natural killer cells and lymphocytes 190 . Zinc has been shown to have antiviral effects against nCov 191 . It enhances the response of both IgM and IgG antibodies. ...
The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) posed a serious threat to human health worldwide. The death toll was immense in many countries, irrespective of their advanced healthcare system. Post-COVID complications are equally challenging. It was realized that a single method to manage the COVID-19 pandemic and related outbreaks is not adequate; rather, an integrated approach which includes spreading awareness and educating masses about the disease, development of antiviral drugs and other safer drugs for symptomatic treatment of the disease, and mass vaccination is needed to manage such pandemic. Plants used in traditional medicine systems contain diverse secondary metabolites. These have been screened against SARS-CoV-2 and have shown effective antiviral activities. Many of the plant products are also useful for symptomatic treatment. The immune-boosting properties of many phytochemicals have been well documented. In this review, the potential of traditional medicinal plants for effective management of the COVID-19 pandemic is presented.
... Т-хелперні клітини стимулюють диференціювання В-лімфоцитів у плазматичні клітини, що продукують спочатку IgM, а потім IgG, максимальні рівні яких у крові визначають на 8-9 добу захворювання. Встановлено, що через 12 тижнів від початку захворювання IgM зникають, а IgG зберігаються протягом тривалого періоду, що визначає захист від реінфікування [49,50]. ...
The COVID-19 epidemic has already come to be seen as an emergency of international concern. This relates not only to the wide occurrence of the infection, but also to a fairly high mortality rate, currently more than 6.5 million deaths in the world. The aim of this study was to analyze, generalize and systematize the currently available literary data on the study of the novel coronavirus infection pathogenesis in the human body and to determine key changes that occur after the SARS-CoV-2 penetration into cells. In this way to target physicians primarily based on the pathogenetic processes that occur in the human body, syndromes and symptom complexes that are observed in treatments. Results. The article presents a literature review demonstrating that the specific interaction between the virus and somatic cells is the triggering mechanism for the pathogenesis of coronavirus infection. The main route for SARS-CoV-2 entry into the body is the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed not only in type 2 alveolar epithelial cells, but also in cells of the kidney, heart, blood vessels and gastrointestinal tract, including endotheliocytes and pericytes. Expression of the ACE2 receptor has also been shown in various structures and parts of the brain, cells of the conjunctiva, limbus, cornea and cells of the substantia propria. A high expression of the ACE2 receptor has been found in the epithelial cells of the oral mucosa, salivary glands, tonsils and tongue. These factors explain a possible involvement of different organs and systems in the development of multiorgan failure. Conclusions. In the development of multiorgan disfunction, two components are important: first, direct cell tropism and viral load, that may be unique in each patient. Secondly, it is the development of immune-mediated reactions to infected cells. Under conditions of hyperimmune inflammation, that is, the development of cytokine storm, acute respiratory distress syndrome progresses, and multiple organ failure develops. Endothelial damage is directly involved in the pathophysiology of this process, that results in the development of endothelial dysfunction, disruption of microcirculation, as well as perivascular inflammation, which aggravates damage to the endothelium and can lead to thrombus formation. The use of modern knowledge about the immunopathogenesis of COVID-19 would help to estimate the risk for severe infection and the possible development of complications, allowing for the timely implementation of effective pathogenetic therapy.
Background: COVID-19 has become the center of attention since its outbreak in December 2019. Despite the discovery of its preventive vaccine, role of healthy immune system is undebatable. Functional foods are continuously hunted as a promising option for a safe natural therapeutic treatment.
Purpose: This review demonstrates how functional foods can boost host immune system, promote antiviral operation, and synthesize biologically effective molecules against SARS-COV-2.
Research Methodology: For current review, online search was conducted for nature-based functional immune boosters against SARS-COV-2.
Conclusion: Functional foods, alongside a healthy lifestyle, fortifies the human immune system and could all help to dramatically lower the cost burden of COVID-19, the suffering of the patients, and the mortality rates worldwide.
Overview: SARS CoV‐2 infection is accompanied by the development of acute inflammation, resolution of which determines the course of infection and its outcome. If not resolved (brought back to preinjury status), the inflamed state progresses to a severe clinical presentation characterized by uncontrolled cytokine release, systemic inflammation, and in some death. In severe CoV‐2 disease, the required balance between protective inflammation and its resolution appears missing, suggesting that the ω‐3–derived specialized proresolving mediators (SPMs) needed for resolution are either not present or present at ineffective levels compared to competing ω‐6 polyunsaturated fatty acid (PUFA) metabolic derivatives.
Aim: To determine whether ω‐6 PUFA linoleic acid (LA) metabolites increased in those infected with severe disease compared to uninfected controls.
Findings: Increased levels of ω‐6 LA metabolites, e.g., arachidonic acid (AA), epoxyeicosatrienoic (EET) acid derivatives of AA (8,9‐, 11,12‐, and 14,15‐EETs), AA‐derived hydroxyeicosatetraenoic (HETE) acid, dihydroxylated diols (leukotoxin and isoleukotoxin), and prostaglandin E2 with decreased levels of ω‐3–derived inflammation resolving SPMs. Therapeutic treatment of SARS CoV‐2 patients with ω‐3 PUFA significantly increased 18‐HEPE (SPM precursor) and EPA‐derived diols (11,12‐ and 14,15‐diHETE), while toxic 9,10‐ and 12,13‐diHOMEs (leukotoxin and iosleukotoxin, respectively) decreased.
Conclusion: Unbalanced dietary intake of ω‐6/ω‐3 PUFAs contributed to SARS CoV‐2 disease severity by decreasing ω‐3–dependent SPM resolution of inflammation and increasing membrane‐associated ferroptotic AA peroxidation.
Background: Diabetes mellitus is an endocrine metabolic disorder, which affects the major organs in human and comorbid with others. Besides, diabetic patients are more prone to various infectious diseases as well as COVID-19 sporadic infection which is a high risk for patients with diabetes mellitus. To combat these infections and comorbid situations, an integrated balanced nutritional supportive could help in maintaining sound health and increase immunity for prevention and management of such type of viral infections. Objectives: While information regarding nutritional supports in COVID-19 pandemic in diabetic patients is not available, this review aimed to accumulate the evidence from previous publications where studied about nutrition-based supports or interventions for viral diseases with special emphasis on respiratory infections. Methods: For reviewing, searches are done for getting journal articles into Google Scholar, Pub Med/Medline, Database of Open Access Journal and Science Direct for relevant data and information. Results: Integrated nutritional supports of both macronutrients and micronutrients guidelines, including home-based physical exercise schedule, is summarized in this comprehensive review for possible prevention and management of diabetic patients in COVID-19 infections. The immune-boosting benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections of diabetic patients are also included. Conclusion: There is an urgent need for a healthy diet and integrated nutritional supports with home-based physical activities for diabetic patients during the self-isolation period of COVID-19 Infection.
This review is intended to evaluate the severity of Coronavirus Disease 2019 (COVID‐19) in hospitalized pediatric patients with obesity. The increased risk of hospitalization in pediatric patients with obesity highlights the need for a thorough investigation into the impact of COVID‐19 in this vulnerable population, given the significant public health challenges obesity presents in this age group. The review followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols) guidelines. A systematic search was conducted in the PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), LILACS (scientific health information from Latin America and the Caribbean countries), Web of Science, Embase, and Scopus databases for relevant articles published between December 2019 and November 2021. Observational studies (cross‐sectional and cohort) involving pediatric patients with obesity who tested positive for COVID‐19, were hospitalized, and had outcomes related to disease severity parameters such as intensive care unit (ICU) admission, length of ICU stay, and mechanical ventilation) were included. The quality of evidence from the included studies was assessed using the Newcastle‒Ottawa Scale. Extracted data included the author, year, country, study design, aim, population, outcomes/severity, and primary results. Eight studies were included in the review. A narrative synthesis was conducted to qualitatively summarize the findings, highlighting that obesity is a potential aggravating factor in the clinical presentation of COVID‐19 among hospitalized pediatric patients. The findings revealed a positive association between the pediatric population with obesity and COVID‐19 severity, particularly among adolescents, who were at greater risk of developing severe illness. This association was also evident in higher rates of ICU admission and increased use of mechanical ventilation.
The global impact of the COVID-19 pandemic has severely affected healthcare systems worldwide. COVID-19 has led to significant morbidity and mortality globally, including substantial cases and deaths in Nigeria. The roles of the healthcare worker in the uptake of the Covid-19 vaccine are enormous in education, information dissemination, building trust, motivation and support, accessibility and logistics, monitoring and follow-up, the importance of their knowledge and attitude is of paramount importance in helping the members of the community to make informed decision, demonstrate positive attitudes, serve as community role models and addressing misinformation. The study aimed to: Asses knowledge and to determine the attitudes of primary healthcare workers towards COVID-19 vaccination compliance in Gusau Metropolis. Descriptive cross-sectional design was employed. 128 primary healthcare workers were sampled. Multistage random sampling was used to select the population. Using a structured questionnaire conducted data collection, the responses were analysed using descriptive statistics for knowledge and attitude and inferential statistics of the Chi-square test to explore the relationship between knowledge and attitudes toward vaccine compliance. Findings showed that 65.6% of respondents possessed good knowledge about the COVID-19 vaccines. The attitudes towards the vaccines were positive, evidenced by an average attitude score of 3.0, indicating favourable vaccine compliance. There was a relationship between the knowledge of covid-19 vaccine and attitudes toward covid-19 vaccine compliance. The study concluded that primary healthcare workers in Gusau are well-informed about COVID-19 and possess positive attitudes towards COVID-19 vaccination.
Los nanomateriales como las nanopartículas de óxido de cobre (CuO NPs) son de suma importancia debido a sus aplicaciones en muy diversos aspectos de la como en la agricultura en la cual permite aumentar las características organolépticas de la parte comestible de la planta. En el presente trabajo consistió en evaluar diferentes concentraciones de NPs de CuO para mostrar su efecto en el rendimiento, calidad del fruto, calidad bioactiva y la concentración del Cu en frutos de sandía. Se evaluaron seis tratamientos de NPs CuO (0, 50, 100, 150, 200, 250 mg L-1). Los resultados muestran que la aplicación foliar de Nps de Cu no afecta el rendimiento; sin embargo, a concentraciones altas aumenta la calidad de fruto, la calidad bioactiva y el contenido de Cu, obteniendo mejores resultados con el tratamiento de 250 mg L-1. Por tanto, con la nanobiofortificación con NPs CuO resulta en frutos de sandía de mejor calidad debido a la acumulación de compuestos bioactivos.
There is an urgent need for preventive and therapeutic drugs to effectively treat and prevent viral diseases from resurfacing as they emerge during the COVID-19 pandemic. This study aims to assess the antiviral effects of four natural compounds commonly used in traditional medicine to treat SARS-CoV-2 infection. A cytotoxicity, dose-dependent, and plaque reduction assay was performed on Vero CCL-81 cells to figure out their effects on the cells. Quantification of cytokines was assessed. In silico analysis for the selected compound was also evaluated. Results revealed that the compounds could disrupt the viral replication cycle through direct inhibition of the virus or immune system stimulation. The cytotoxicity assay results revealed that the compounds were well tolerated by the cells, indicating that the compounds were not toxic to the cells. This study evaluated the antioxidant capacities of propolis, curcumin, quercetin, and ginseng using ABTS, FRAP, and CUPRAC assays, revealing that propolis exhibited the highest antioxidant activity of ABTS with 1250.40 ± 17.10 μmol Trolox eq/g, with FRAP values reaching 1200.55 ± 15.90 μmol Fe ² ⁺ eq/g and CUPRAC values of 1150.80 ± 14.20 μmol Trolox eq/g at 1000 µg/mL, highlighting its potential as a potent natural antioxidant. The results of the plaque reduction assay revealed that the compounds could reduce the size and number of plaques, indicating that the compounds could inhibit the virus replication cycle. Subsequently, using molecular docking to analyze the effect of propolis, curcumin, quercetin, and ginseng as inhibitors, it was unveiled that the four compounds are likely to have the potential to inhibit the protease activity, spike protein S1, and RNA polymerase of SARS-CoV-2 and the virus titer was reduced by 100% after post-infection using propolis as an inhibitor control.
Graphical Abstract
Medical nutrition therapy (MNT) represents an outcome-defining factor in the intensive care unit (ICU). During the COVID-19 pandemic, acute respiratory distress syndrome (ARDS) cases dramatically increased, making MNT in ICU even more challenging. Extracorporeal membrane oxygenation (ECMO) is a life-saving support in ARDS patients, but no specific MNT guidelines exist.
Inflammation is the key pathophysiological process at the base of ARDS and COVID-19 illness. The inflammatory process increases catabolism and energy requests, thus making malnutrition in these populations extremely common and difficult to deal with. In addition, other typical characteristics of these patients need to be considered, like the high comorbidity burden and the different peculiarities of the illness phases. Invasive and noninvasive ventilation, prone position, and altered gas exchanges all influence the different aspects of MNT, such as timing for initiation of nutrition, diet type and amount, and administration route.
Finally, nutritional support during ECMO becomes even more challenging, dealing with a cohort of extremely severe patients, a high risk of adverse events, and the lack of evidence.
It is thus clear that MNT management should include a comprehensive knowledge of these conditions, as the right nutritional support may improve relevant clinical outcomes, like mortality and quality of life.
Dünya ekonomisinde önemli bir payı olan turizm sektörü Covid-19 pandemisi nedeniyle derinden etkilenmiştir. Gerek sınırlama önlemleri gerekse seyahat yasaklarından kaynaklı olarak ulusal ve uluslararası turizm akışı sekteye uğramıştır. Bu çalışmada; Covid-19 virüsünün, insanların 2022 yılı yaz sezonu için planmış oldukları tatil deneyimleri üzerindeki etkilerinin incelenmesi amaçlanmıştır. Nitel veri toplama yöntemlerinden görüşme tekniği kullanılarak yürütülen çalışmada, Siirt ve Konya il merkezinde görev yapan her yıl tatil deneyimi olan akademisyenler örnekleme dahil edilmiştir. Çalışmada elde edilen veriler belirlenen tema ve kodlara ayrılarak içerik analizi tekniğiyle çözümlenmiştir. Araştırma sonucunda; katılımcıların tatil tercihlerinde tatil sürecine etki eden faktörlerin başında hijyen ve sosyal mesafe kriterlerinin geldiği, tatil süresince ağırlıklı olarak konser ve tiyatro gibi eğlence yerlerine gitmeyi ve yeme-içeme aktiveleri için herhangi bir önlem almayı düşünmedikleri, yoğun olarak kültür turizmi deneyimi için, Ege Bölgesi başta olmak üzere yurtiçinde, kendi özel araçları ile birlikte, 7-14 gün süreliğine ve yazlık/kiralık villa gibi yerlerde konaklamayı planladıkları sonuçlarına ulaşılmıştır.
Background: Limited clinical data are available regarding the impacts of coronavirus disease 2019 (COVID-19) on children.
Objective: This study assessed the clinical characteristics, nutritional status, and disease severity in pediatric patients with COVID-19.
Methods: A retrospective study examined medical records of children with COVID-19 admitted to Abuzar Hospital (Ahvaz, Iran) for nine months. Data related to their clinical, nutritional status
and demographic characteristics were documented.
Results: The present study included medical records of 500 patients. More than half of them were boys. Different levels of COVID-19 severity were observed in 202, 172, and 126 children as mild, moderate, and severe cases, respectively. Children with severe or moderate COVID-19 had substantially elevated levels of various inflammatory markers, blood urea nitrogen (BUN), gamma-glutamyl transferase (GGT), neutrophils, alanine transaminase (ALT), creatinine, bilirubin, and aspartate aminotransferase (AST) compared to those with mild COVID-19 (p < 0.001). They had lower levels of lymphocytes and vitamin D, as well as longer hospital stays than children with mild COVID-19 (p < 0.001). In addition, 52% and 40.2% of patients had malnutrition and anemia, respectively.
The majority of underweight and stunted children had moderate or severe COVID-19.
Conclusion: The current study revealed a high prevalence of malnutrition, anemia, insufficient levels of vitamin D, elevated levels of inflammatory markers, and abnormal liver and kidney function tests in children with severe or moderate cases of COVID-19 compared to those with mild COVID-19.
Main conclusion
Biofortification of legumes using diverse techniques such as plant breeding, agronomic practices, genetic modification, and nano-technological approaches presents a sustainable strategy to address micronutrient deficiencies of underprivileged populations.
Abstract
The widespread issue of chronic malnutrition, commonly referred to as "hidden hunger," arises from the consumption of poor-quality food, leading to various health and cognitive impairments. Biofortified food crops have been a sustainable solution to address micronutrient deficiencies. This review highlights multiple biofortification techniques, such as plant breeding, agronomic practices, genetic modification, and nano-technological approaches, aimed at enhancing the nutrient content of commonly consumed crops. Emphasizing the biofortification of legumes, this review employs bibliometric analysis to examine research trends from 2000 to 2023. It identifies key authors, influential journals, contributing countries, publication trends, and prevalent keywords in this field. The review highlights the progress in developing biofortified crops and their potential to improve global nutrition and help underprivileged populations.
Nutrition is essential in developing and maintaining a robust immune system and is vital for immune homeostasis. The pediatric population is particularly vulnerable to dietary changes, as their growth and development require a high energy intake. Malnutrition in infants can have immediate and long-lasting effects, increasing the risk of morbidity and mortality. Under and overnutrition can slow down the immune response to infections, which can delay recovery. To effectively defend against SARS-CoV-2 infection and enhance viral clearance, it is essential to maintain a healthy diet that includes sufficient macro and micronutrients. Several studies, most of which have been performed in adults, have shown that vitamins such as C, B12, folate, D, and E, as well as the minerals selenium, copper, iron, zinc, and magnesium, can help reduce the symptoms and duration of an infection. Supplementation with micronutrients has been shown to help with childhood malnutrition and can contribute to a more favorable clinical course of COVID-19. In children with obesity, it is also essential to monitor cardiometabolic and thrombotic risks, based on data from studies in adults. This review analyses the impact of the nutritional status of pediatric patients with SARS-CoV-2 infection, its contribution to clinical severity, and potential therapeutic interventions.
Background:
The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP.
Methods:
We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number.
Results:
Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9).
Conclusions:
On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).
A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.
Highlights
• The general features of coronaviruses are introduced.
• The risk of emerging coronaviruses including the 2019‐nCoV is described.
• The genome structure and replication mechanism of coronaviruses are provided.
• The diseases caused by the major coronaviruses are listed.
Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections. Remdesivir (RDV) is a broad-spectrum antiviral drug with activity against MERS coronavirus, but in vivo efficacy has not been evaluated. Here, the authors show that RDV has superior anti-MERS activity in vitro and in vivo compared to combination therapy with lopinavir, ritonavir and interferon beta and reduces severe lung pathology.
There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.
Thymosin alpha1 (Tα1), an endogenous peptide first isolated from the thymic tissue in the mid-sixties, has gained considerable attention for its immunostimulatory activity that led to its application to diverse pathological conditions, including cancer. Studies in animal models and human patients have shown promising results in different types of malignancies, especially when Tα1 was used in combination with other chemo- and immune therapies. For this reason, the advancements in our knowledge on the adjuvant role of Tα1 have moved in parallel with the development of novel cancer therapies in a way that Tα1 was integrated to changing paradigms and protocols, and tested for increased efficacy and safety. Cancer immunotherapy has recently experienced a tremendous boost following the development and clinical application of immune checkpoint inhibitors. By unleashing the full potential of the adaptive immune response, checkpoint inhibitors were expected to be very effective against tumors, but it soon became clear that a widespread and successful application was not straightforward and shortcomings in efficacy and safety clearly emerged. This scenario led to the development of novel concepts in immunotherapy and the design of combination protocols to overcome these limitations, thus opening up novel opportunities for Tα1 application. Herein, we summarize in a historical perspective the use of Tα1 in cancer, with particular reference to melanoma, hepatocellular carcinoma and lung cancer. We will discuss the current limitations of checkpoint inhibitors in clinical practice and the mechanisms at the basis of a potential application of Tα1 in combination protocols.
Reactive oxygen species (ROS) are frequently produced during viral infections. Generation of these ROS can be both beneficial and detrimental for many cellular functions. When overwhelming the antioxidant defense system, the excess of ROS induces oxidative stress. Viral infections lead to diseases characterized by a broad spectrum of clinical symptoms, with oxidative stress being one of their hallmarks. In many cases, ROS can, in turn, enhance viral replication leading to an amplification loop. Another important parameter for viral replication and pathogenicity is the nutritional status of the host. Viral infection simultaneously increases the demand for micronutrients and causes their loss, which leads to a deficiency that can be compensated by micronutrient supplementation. Among the nutrients implicated in viral infection, selenium (Se) has an important role in antioxidant defense, redox signaling and redox homeostasis. Most of biological activities of selenium is performed through its incorporation as a rare amino acid selenocysteine in the essential family of selenoproteins. Selenium deficiency, which is the main regulator of selenoprotein expression, has been associated with the pathogenicity of several viruses. In addition, several selenoprotein members, including glutathione peroxidases (GPX), thioredoxin reductases (TXNRD) seemed important in different models of viral replication. Finally, the formal identification of viral selenoproteins in the genome of molluscum contagiosum and fowlpox viruses demonstrated the importance of selenoproteins in viral cycle.
Anemia affects approximately 30% of children all over the world. Acute respiratory tract infections (ARTI), urinary tract infections (UTI) and gastroenteritis (GE) are common infectious entities in children. Here, we assessed the association between anemia and development of recurrent ARTI, UTI, and GE in children.
This was a case-control study in hospitalized 2 -5 years old children in Professorial Pediatric Unit at Teaching Hospital Anuradhapura, Sri Lanka. An 18-month follow up was done to assess the risk factors for the development of recurrent ARTI, GE, UTI, and control presented without infections. Further, 6-month follow up done after 3-month iron supplementation to assess the occurrence of recurrences. Blood Hb concentration was measured using Drabking’s reagent. Logistic regression was used to find the risk factors for the development of recurrences.
In ARTI, 121/165 (73.3%), GE, 88/124 (71 %), UTI 46/96 (47.9 %) and control 40/100 (40%) were having anemia. Initial ARTI group, recurrent ARTI was 24 (14.5 %, p=0.03); initial GE group: recurrent GE was 14 (11.3 %, p=0.03), recurrent ARTI was 11 (8.9 %, p=0.04); initial UTI group, development of; recurrent UTI was 8 (8.3 %, p=0.04); control, recurrent ARTI was 11 (11 %, p=0.03). Following 3-month iron supplementation reduction of recurrences was significant: initial ARTI recurrent ARTI in 90%, recurrent GE in 77.7%; initial GE recurrent GE in 83.3%, recurrent ARTI in 80%; initial UTI recurrent ARTI in 71.4 % and control recurrent ARTI in 88.8 %.
Iron deficiency is a major type of anemia and anemic children are more prone to develop recurrent ARTI and GE. Once iron deficiency being corrected the rate of recurrent ARTI and GE was reduced. This would be a boost for policy developers to implement strategies at the community level to prevent iron deficiency in children to reduce ARTI and GE recurrences.
Background
Coronaviruses (CoVs) primarily cause enzootic infections in birds and mammals but, in the last few decades, have shown to be capable of infecting humans as well. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and, more recently, Middle-East respiratory syndrome (MERS) has demonstrated the lethality of CoVs when they cross the species barrier and infect humans. A renewed interest in coronaviral research has led to the discovery of several novel human CoVs and since then much progress has been made in understanding the CoV life cycle. The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis. Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins.
Main body
This review aims to establish the current knowledge on CoV E by highlighting the recent progress that has been made and comparing it to previous knowledge. It also compares E to other viral proteins of a similar nature to speculate the relevance of these new findings. Good progress has been made but much still remains unknown and this review has identified some gaps in the current knowledge and made suggestions for consideration in future research.
Conclusions
The most progress has been made on SARS-CoV E, highlighting specific structural requirements for its functions in the CoV life cycle as well as mechanisms behind its pathogenesis. Data shows that E is involved in critical aspects of the viral life cycle and that CoVs lacking E make promising vaccine candidates. The high mortality rate of certain CoVs, along with their ease of transmission, underpins the need for more research into CoV molecular biology which can aid in the production of effective anti-coronaviral agents for both human CoVs and enzootic CoVs.
Vaccination with a live bivalent vaccine of Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) is a routine practice in poultry industry in China. This study was designed to evaluate ginseng stem-leaf saponins (GSLS) in combination with selenium (Se) for their adjuvant effect on the immune response to vaccination against NDV and IBV in chickens. A live bivalent vaccine of NDV and IBV was diluted in saline solution containing GSLS or Se or both and used to immunize chickens via a intraocular-and-intranasal route. Results showed that GSLS promoted significantly higher NDV- and IBV-specific antibody responses with the highest antibody response detected in GSLS-Se group. The increased antibody was capable of neutralizing NDV and IBV. In addition, GSLS-Se enhanced lymphocyte proliferation and production of IFN-γ and IL-4. More importantly GSLS-Se was found to promote early production and prolong the duration of the antibody responses. In order to improve the efficacy of vaccination in chicken flocks, the diluent containing GSLS-Se deserves further studies to evaluate its effect on other chicken vaccines.
Bats are speculated to be reservoirs of several emerging viruses including coronaviruses (CoVs) that cause serious disease in humans and agricultural animals. These include CoVs that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), porcine epidemic diarrhea (PED) and severe acute diarrhea syndrome (SADS). Bats that are naturally infected or experimentally infected do not demonstrate clinical signs of disease. These observations have allowed researchers to speculate that bats are the likely reservoirs or ancestral hosts for several CoVs. In this review, we follow the CoV outbreaks that are speculated to have originated in bats. We review studies that have allowed researchers to identify unique adaptation in bats that may allow them to harbor CoVs without severe disease. We speculate about future studies that are critical to identify how bats can harbor multiple strains of CoVs and factors that enable these viruses to “jump” from bats to other mammals. We hope that this review will enable readers to identify gaps in knowledge that currently exist and initiate a dialogue amongst bat researchers to share resources to overcome present limitations.
Vitamin E (VE) has a recognized leading role as a contributor to the protection of cell constituents from oxidative damage. However, evidence suggests that the health benefits of VE go far beyond that of an antioxidant acting in lipophilic environments. In humans, VE is channeled toward pathways dealing with lipoproteins and cholesterol, underlining its relevance in lipid handling and metabolism. In this context, both VE intake and status may be relevant in physiopathological conditions associated with disturbances in lipid metabolism or concomitant with oxidative stress, such as obesity. However, dietary reference values for VE in obese populations have not yet been defined, and VE supplementation trials show contradictory results. Therefore, a better understanding of the role of genetic variants in genes involved in VE metabolism may be crucial to exert dietary recommendations with a higher degree of precision. In particular, genetic variability should be taken into account in targets concerning VE bioavailability per se or concomitant with impaired lipoprotein transport. Genetic variants associated with impaired VE liver balance, and the handling/resolution of oxidative stress might also be relevant, but the core information that exists at present is insufficient to deliver precise recommendations.
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MVvac2-MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MVvac2-MERS-S(H) or novel MVvac2-MERS-N were further characterized. We focused on the necessity for vector replication and the nature of induced T cells, since functional CD8+ T cells contribute importantly to clearance of MERS-CoV. While no immunity against MERS-CoV or MV was detected in MV-susceptible mice after immunization with UV-inactivated virus, replication-competent MVvac2-MERS-S(H) triggered robust neutralizing antibody titers also in adult mice. Furthermore, a significant fraction of MERS CoV-specific CD8+ T cells and MV-specific CD4+ T cells simultaneously expressing IFN-γ and TNF-α were induced, revealing that MVvac2-MERS-S(H) induces multifunctional cellular immunity.
Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis. The effect of EVs on replication of HCV was assessed in coculture models. Functional analyses were performed to assess the impact of PUFAs on EV-mediated antiviral immunity. We found that macrophages secreted various cytokines shortly after stimulation with type I and II IFN, which orchestrated a fast but short-lasting antiviral state. This rapid innate immune answer was followed by the production of macrophage-derived EVs, which induced a late, but long-lasting inhibitory effect on HCV replication. Of note, exposure of macrophages to PUFAs, which are important regulators of immune responses, dampened EV-mediated antiviral immune responses. Finally, EVs from patients with hepatitis C exhibited long-lasting antiviral activities during IFN therapy as well. The antiviral effect of EVs from Caucasian and Japanese patients differed, which may be explained by different nutritional uptake of PUFAs. In conclusion, our data indicate that macrophage-derived EVs mediate long-lasting inhibitory effects on HCV replication, which may bridge the time until efficient adaptive immune responses are established, and which can be blunted by PUFAs.
Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs in vitro and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs. Here, we show that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC50) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Passage of WT MHV in the presence of the GS-5734 parent nucleoside selected two mutations in the nsp12 polymerase at residues conserved across all CoVs that conferred up to 5.6-fold resistance to GS-5734, as determined by EC50. The resistant viruses were unable to compete with WT in direct coinfection passage in the absence of GS-5734. Introduction of the MHV resistance mutations into SARS-CoV resulted in the same in vitro resistance phenotype and attenuated SARS-CoV pathogenesis in a mouse model. Finally, we demonstrate that an MHV mutant lacking ExoN proofreading was significantly more sensitive to GS-5734. Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.
IMPORTANCE
Coronaviruses (CoVs) cause severe human infections, but there are no approved antivirals to treat these infections. Development of nucleoside-based therapeutics for CoV infections has been hampered by the presence of a proofreading exoribonuclease. Here, we expand the known efficacy of the nucleotide prodrug remdesivir (GS-5734) to include a group β-2a CoV. Further, GS-5734 potently inhibits CoVs with intact proofreading. Following selection with the GS-5734 parent nucleoside, 2 amino acid substitutions in the nsp12 polymerase at residues that are identical across CoVs provide low-level resistance to GS-5734. The resistance mutations decrease viral fitness of MHV in vitro and attenuate pathogenesis in a SARS-CoV animal model of infection. Together, these studies define the target of GS-5734 activity and demonstrate that resistance is difficult to select, only partial, and impairs fitness and virulence of MHV and SARS-CoV, supporting further development of GS-5734 as a potential effective pan-CoV antiviral.
Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids from Pterogyne nitens on the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids 1 and 2 inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid 2 block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid 1 activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of 1 and 2 possessing in vitro anti-HCV activity.
Vitamin C, vitamin E, and alpha-lipoic acid (ALA) are potent nutritional antioxidants, which are important for enhancing immunity. This study compared the effects of supplementation with vitamin C, vitamin E, or ALA on the antioxidant defense system and the expression of immune-related genes under oxidative stress induced by dexamethasone (DEX) in broilers. In total, 240 one-day-old female Recessive White Rock chickens were assigned randomly to either a basal diet (control group) or basal diet supplemented with vitamin C (200 mg/kg diet), vitamin E (100 mg/kg), or ALA (500 mg/kg) for 28 d starting from hatching. At 21 d of age, birds fed the ALA-supplemented diet had the highest plasma total antioxidant capacity (T-AOC) and superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) enzyme activities, and the lowest plasma malondialdehyde (MDA) activity, as well as the lowest mRNA gene expression levels of interferon gamma (IFN-γ) and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF). At 23 d of age, the broilers in the 3 treatment groups were injected in the thigh muscle with DEX for 3 alternating days. In addition, the control group was divided into 2 equal groups, in which one was injected with saline and the other was injected with DEX. At 28 d of age, the DEX-ALA group (P < 0.05) had the highest activity levels for T-AOC, T-SOD, and GSH-PX in the plasma and liver (P < 0.05), and the greatest reduction in the MDA level. Dietary ALA significantly decreased the mRNA expression levels of the interleukin 1 β (IL-1β), IL-6, IFN-γ, and LITAF genes compared with the other groups during oxidative stress by DEX. In conclusion, this study suggests that in broilers, ALA is more effective for normalizing the oxidative stress induced by DEX than vitamin C or vitamin E.
Background:
The molecular nature of lipoic acid (LA) clarifies its capability of taking part to a variety of biochemical reactions where redox state is meaningful. The pivotal action of LA is the antioxidant activity due to its ability to scavenge and inactivate free radicals. Furthermore, LA has been shown to chelate toxic metals both directly and indirectly by its capability to enhance intracellular glutathione (GSH) levels. This last property is due to its ability to interact with GSH and recycle endogenous GSH. LA exhibits significant antioxidant activity protecting against oxidative damage in several diseases, including neurodegenerative disorders. Interestingly, LA is unique among natural antioxidants for its capability to satisfy a lot of requirements, making it a potentially highly effective therapeutic agent for many conditions related with oxidative damage. In particular, there are evidences showing that LA has therapeutic activity in lowering glucose levels in diabetic conditions. Similarly, LA supplementation has multiple beneficial effects on the regression of the mitochondrial function and on oxidative stress associated with several diseases and aging.
Aim:
The aim of the present review is to describe the molecular mechanisms underlying the beneficial effects of LA under various experimental conditions and disease and how to exploit such effect for clinical purposes.
Conclusion:
LA has pleiotropic effects in different pathways related with several diseases, its use as a potential therapeutic agent is very promising.
Background:
Measles is an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. This is an update of a review first published in 2015.
Objectives:
To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles.
Search methods:
We searched CENTRAL (03 February 2017, Issue 2), MEDLINE (1946 to 03 February 2017), Embase (1974 to 03 February 2017), CINAHL (1981 to 03 February 2017), LILACS (1982 to 03 February 2017), Web of Science (1985 to 03 February 2017), and BIOSIS Previews (1985 to 27 June 2014). We also searched ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 03 February 2017 to identify unpublished and ongoing studies.
Selection criteria:
Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles.
Data collection and analysis:
Two review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions, and other study characteristics using a standardised data extraction form. We used risk ratio (RR) and hazard ratio (HR) as measures of effect with 95% confidence intervals (CI). We included only one study, and did not conduct meta-analysis.
Main results:
We did not identify any new studies for inclusion in this update. One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed no significant difference in mortality between children with measles and pneumonia who received zinc supplements and those who received placebo (RR 0.34, 95% CI 0.01 to 8.14). There was no significant difference in time to absence of fever between children who received zinc supplements and those who did not (HR 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. We assessed the overall quality of the evidence as very low.
Authors' conclusions:
We could not draw any definitive conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in children with measles.
Background
Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that causes severe morbidity and mortality. Up to date, there is no approved or licensed vaccine or antiviral medicines can be used to treat MERS-CoV-infected patients. Here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against MERS-CoV infection. Methods
We performed MTT and neutral red uptake assays to assess the survival rates of MERS-infected Vero E6 cells. In addition, quantitative PCR, western blotting, and immunofluorescent assays determined the intracellular viral RNA and protein expression. For viral productivity, we utilized plaque assays to confirm the antiviral properties of resveratrol against MERS-CoV. ResultsResveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment. Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV. Conclusion
In this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro. We perceive that resveratrol can be a potential antiviral agent against MERS-CoV infection in the near future.
Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.
Cyclophilin A (CypA) is a key member of immunophilins that has peptidyl-prolyl cis/trans isomerase (PPIase) activity. Besides acting as a cellular receptor for immunosuppressive drug cyclosporine A (CsA), CypA is involved in various cellular activities. CypA has an important role in viral infection which either facilitates or inhibits their replication. Inhibition of CypA via inhibitors is useful for overcoming some viral infections, indicating that CypA is an attractive target for anti-viral therapy. Collectively, these facts demonstrate the critical roles of CypA in mediating or inhibiting viral infections, suggesting that CypA can be an attractive cellular target for the development of anti-viral therapy.
Importance:
There are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, like Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses like hepatitis B virus or human herpes virus 8 (HHV-8) establish persistent infections that cause chronic illnesses including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug Arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus, Tacaribe arenavirus, and HHV-8, and propose ARB as a broad-spectrum antiviral drug that may be useful against hemorrhagic viruses.
Passive immunisation for the prevention and treatment of human infectious diseases can be traced back to the 20 th century. The recent Ebola virus outbreak in West Africa has turned the spotlight onto the possible use of convalescent whole blood and convalescent plasma in the treatment of infectious diseases because they are the only therapeutic strategy available in some cases, given the unavailability of vaccines, drugs or other specific treatments. Convalescent blood products could be a valid option in the treatment/prophylaxis of several infectious diseases both in association with other drugs/preventive measures and as the only therapy when a specific treatment is not available. However, there are still some issues to consider in determining the advisability of implementing a large-scale convalescent plasma transfusion programme.
Since the first report of Middle East respiratory syndrome (MERS) in 2012 in Saudi Arabia, no standard treatment guideline has been set despite the virulence of MERS-CoV and the high case-fatality rate. The outbreak in South Korea in 2015 demonstrates that MERS outbreaks can occur outside of the Middle East. The combination of ribavirin and interferon-α has been the most widely used therapy for this infection. However, due to the varying results of treatment with these drugs, a new antiviral combination regimen is urgently needed. This is a case report of use of lopinavir/ritonavir-based combination antiviral therapy for a patient with MERS-CoV infection.
Corneal transplantation is the most commonly performed tissue transplant boasting over a century of history, science, and tradition. While favorable outcomes have been reported after penetrating keratoplasty, rejection remains a major cause of graft failure. The long-term survival rates of this relatively immunologically privileged tissue are only just comparable to those of vascularized organs. While corticosteroids treatment remains the gold standard for postoperative immunomodulation, other agents have been utilized in an ongoing effort to improve graft survival and patient outcomes. One of the most promising immunomodulatory substances whose immunosuppressive effect has revolutionized solid organ transplantation is cyclosporine (CsA). A calcineurin inhibitor, cyclosporine has been used as an immunosuppressive agent in corneal transplantation since the 1980's. Although some studies have shown beneficial effects of cyclosporine in both low- and high-risk corneal transplant patients the use of cyclosporine in rejection prophylaxis and treatment remain controversial and disputable. We herein present a literature review on the role of systemic cyclosporine in corneal transplantation.
Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase which is highly homologous to angiotensin-converting enzyme (ACE). ACE2 produces vasodilator peptides angiotensin 1-7 from angiotensin II. In the present study, we synthesized various internally quenched fluorogenic (IQF) substrates (fluorophore-Xaa-Pro-quencher) based on the cleavage site of angiotensin II introducing N-terminal fluorophore N-methylanthranilic acid (Nma) and C-terminal quencher N(ε)-2,4- dinitrophenyl-lysine [Lys(Dnp)]. The synthesized mixed substrates "Nma-Xaa-Pro-Lys(Dnp)" were hydrolyzed by recombinant human (rh) ACE2. The amount of each product was determined by liquid chromatography mass spectrometry (LC-MS) with fluorescence detection and it was found that Nma-His-Pro-Lys(Dnp) is the most suitable substrate for rhACE2. The Km, kcat, and kcat/Km values of Nma-His-Pro-Lys(Dnp) on rhACE2 were determined to be 23.3 μM, 167 s(-1), and 7.17 μM(-1) s(-1), respectively. Using the rhACE2 and the newly developed IQF substrate, we found rhACE2 inhibitory activity in soybean and isolated the active compound soybean ACE2 inhibitor (ACE2iSB). The physicochemical data on the isolated ACE2iSB were identical to those of nicotianamine. ACE2iSB strongly inhibited rhACE2 activity with an IC50 value of 84 nM. This is the first demonstration of an ACE2 inhibitor from foodstuffs.
Background:
Ventilator-induced lung injury is a form of acute lung injury that develops in critically ill patients on mechanical ventilation and has a high degree of mortality. Nicotinamide phosphoribosyltransferase is an enzyme that is highly upregulated in ventilator-induced lung injury and exacerbates the injury when given exogenously. Nicotinamide (vitamin B3) directly inhibits downstream pathways activated by Nicotinamide phosphoribosyltransferase and is protective in other models of acute lung injury.
Methods:
We administered nicotinamide i.p. to mice undergoing mechanical ventilation with high tidal volumes to study the effects of nicotinamide on ventilator-induced lung injury. Measures of injury included oxygen saturations and bronchoalveolar lavage neutrophil counts, protein, and cytokine levels. We also measured expression of nicotinamide phosophoribosyltransferase, and its downstream effectors Sirt1 and Cebpa, Cebpb, Cebpe. We assessed the effect of nicotinamide on the production of nitric oxide during ventilator-induced lung injury. We also studied the effects of ventilator-induced lung injury in mice deficient in C/EBPε.
Results:
Nicotinamide treatment significantly inhibited neutrophil infiltration into the lungs during ventilator-induced lung injury, but did not affect protein leakage or cytokine production. Surprisingly, mice treated with nicotinamide developed significantly worse hypoxemia during mechanical ventilation. This effect was not linked to increases in nitric oxide production or alterations in expression of Nicotinamide phosphoribosyl transferase, Sirt1, or Cebpa and Cebpb. Cebpe mRNA levels were decreased with either nicotinamide treatment or mechanical ventilation, but mice lacking C/EBPε developed the same degree of hypoxemia and ventilator-induced lung injury as wild-type mice.
Conclusions:
Nicotinamide treatment during VILI inhibits neutrophil infiltration of the lungs consistent with a strong anti-inflammatory effect, but paradoxically also leads to the development of significant hypoxemia. These findings suggest that pulmonary neutrophilia is not linked to hypoxemia in ventilator-induced lung injury, and that nicotinamide exacerbates hypoxemia during VILI.
Purpose
This study describes the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia.
Patients and methods
Epidemiological analysis was performed on data from all MERS-CoV cases recorded by the Saudi Ministry of Health between June 6, 2013 and May 14, 2014. The frequency of cases and deaths was calculated and adjusted by month, sex, age group, and region. The average monthly temperature and humidity of infected regions throughout the year was also calculated.
Results
A total of 425 cases were recorded over the study period. The highest number of cases and deaths occurred between April and May 2014. Disease occurrence among men (260 cases [62%]) was higher than in women (162 cases [38%]), and the case fatality rate was higher for men (52%) than for women (23%). In addition, those in the 45–59 years and ≥60 years age groups were most likely to be infected, and the case fatality rate for these people was higher than for other groups. The highest number of cases and deaths were reported in Riyadh (169 cases; 43 deaths), followed by Jeddah (156 cases; 36 deaths) and the Eastern Region (24 cases; 22 deaths). The highest case fatality rate was in the Eastern Region (92%), followed by Medinah (36%) and Najran (33%). MERS-CoV infection actively causes disease in environments with low relative humidity (<20%) and high temperature (15°C–35°C).
Conclusion
MERS-CoV is considered an epidemic in Saudi Arabia. The frequency of cases and deaths is higher among men than women, and those above 45 years of age are most affected. Low relative humidity and high temperature can enhance the spread of this disease in the entire population. Further analytical studies are required to determine the source and mode of infection in Saudi Arabia.
Studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease; however, there is a paucity of information regarding the effect of acute infection on the vitamin status of the vitamin-replete neonate. To characterize the effects of acute infection on vitamin D and E status of the neonate, 6 vitamin-replete preruminant Holstein bull calves were experimentally infected with bovine viral diarrhea virus (BVDV; strain BVDV2-1373). Six mock-inoculated calves served as controls. Sustained pyrexia, leukopenia, and asynchronous increases in serum haptoglobin and serum amyloid A characterized the response of calves to infection with BVDV. Infection was also associated with increased serum IFN-γ, IL-2, and IL-6 concentrations. During the last 8 d of the 14-d postinoculation period, serum 25-hydroxyvitamin D and α-tocopherol concentrations in infected calves decreased by 51 and 82%, respectively. The observed inverse association between vitamin D and E status and serum amyloid A in infected calves suggests that the infection-induced acute phase response contributed to the reduced vitamin status of these animals. Additional studies are necessary to determine if the negative effect of infection on status are unique to this specific infection model or is representative of preruminant calf's response to acute infection. Studies are also needed to characterize mechanisms underlying infection-related changes in vitamin D and E status and to determine whether additional vitamin D or E supplementation during an acute infection diminishes disease severity and duration in the young animal.
An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
Pneumonia outbreak in Wuhan appears to subside, but the virus could re-emerge.
Respiratory tract viral infection caused by viruses or bacteria is one of the most common diseases in human worldwide, while those caused by emerging viruses, such as the novel coronavirus, 2019‐nCoV that caused the pneumonia outbreak in Wuhan, China most recently, have posed great threats to global public health. Identification of the causative viral pathogens of respiratory tract viral infections is important to select an appropriate treatment, save people's lives, stop the epidemics, and avoid unnecessary use of antibiotics. Conventional diagnostic tests, such as the assays for rapid detection of antiviral antibodies or viral antigens, are widely used in many clinical laboratories. With the development of modern technologies, new diagnostic strategies, including multiplex nucleic acid amplification and microarray‐based assays, are emerging. This review summarizes currently available and novel emerging diagnostic methods for the detection of common respiratory viruses, such as influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus, and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. It is anticipated that such data will assist researchers and clinicians to develop appropriate diagnostic strategies for timely and effective detection of respiratory virus infections.
Research Highlights
• Respiratory tract viral infection including 2019‐nCoV poses great threats worldwide. Currently available and novel emerging diagnostic methods are summarized for several common respiratory viruses, including influenza virus, human respiratory syncytial virus, coronavirus, human adenovirus and human rhinovirus. Multiplex assays for simultaneous detection of multiple respiratory viruses are also described. This review is aimed to assist researchers and clinicians to develop timely and effective diagnostic strategies to detect respiratory virus infections.
Middle‐East Respiratory Syndrome‐Coronavirus (MERS‐CoV) is a zoonotic virus transmitted between animals and human beings. It causes MERS with high mortality rate. However, no vaccine or specific treatment is currently available. Since antiviral activity of some flavonoids are known, we applied a flavonoid library to probe inhibitory compounds against MERS‐CoV 3C‐like protease (3CLpro). Herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside and helichrysetin were found to block the enzymatic activity of MERS‐CoV 3CLpro. The binding of the four flavonoids was also confirmed independently using a tryptophan‐based fluorescence method. The systematic comparison of the binding affinity of flavonoids made it possible to infer their scaffolds and functional groups required to bind with MERS‐CoV 3CLpro. An induced‐fit docking analysis revealed that S1 and S2 sites play a role in interaction with flavonoids. The experimental and computational study showed that flavonol and chalcone are favorite scaffolds to bind with the catalytic site of MERS‐CoV 3CLpro. It was also deduced that some flavonoid derivatives with hydrophobic or carbohydrate attached to their core structures have a good inhibitory effect. Therefore, we suggest that flavonoids with these characteristics can be used as templates to develop potent MERS‐CoV 3CLpro inhibitors. This article is protected by copyright. All rights reserved. MERS‐CoV 3CLpro was assayed with a flavonoid library and some chalcone derivatives represented promising inhibitory activity. The docking study confirmed the experimental measurement of the better efficacy of helichrysetin than cardamonin. This study showed the antiviral effect of flavonoids in the atomic level.
Introduction: Thymosin alpha 1 (Ta1) is a natural occurring peptide hormone that is crucial for the maintenance of the organism homeostasis. It has been chemically synthesized and used in diseases where the immune system is hindered or malfunctioning.
Areas covered: Many clinical trials investigate the Ta1 effects in patients with cancer, infectious diseases and as a vaccine enhancer. The number of diseases that could benefit from Ta1 treatment is increasing. To date, questions remain about the physiological basal levels of Ta1 and the most effective dose and schedule of treatment. Evidence is growing that diseases characterized by deregulation of immune and/or inflammatory responses are associated with serum levels of Ta1 significantly lower than those of healthy individuals: to date, B hepatitis, psoriatic arthritis, multiple sclerosis and sepsis. The sputum of cystic fibrosis patients contains lower levels of Ta1 than healthy controls. These data are consistent with the role of Ta1 as a regulator of immunity, tolerance and inflammation.
Expert opinion: Low serum Ta1 levels are predictive and/or associated with different pathological conditions. In case of Ta1 treatment, it is crucial to know the patient’s baseline serum Ta1 level to establish effective treatment protocols and monitor their effectiveness over time.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles.
Because both the host and pathogen require iron, the innate immune response carefully orchestrates control over iron metabolism to limit its availability during times of infection. Nutritional iron deficiency can impair host immunity, while iron overload can cause oxidative stress to propagate harmful viral mutations. An emerging enigma is that many viruses use the primary gatekeeper of iron metabolism, the transferrin receptor, as a means to enter cells. Why and how this iron gate is a viral target for infection are the focus of this review. Expected final online publication date for the Annual Review of Nutrition Volume 38 is August 21, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Infectious disease epidemics match wars and natural disasters in their capacity to threaten lives and damage economies. Like SARS previously and Zika recently, the Ebola crisis in 2015 showed how vulnerable the world is to these epidemics, with over 11,000 people dying in the outbreak. In addition to causing immense human suffering, these epidemics particularly affect low- and middle-income countries. Many of these deadly infectious diseases that have epidemic potential can become global health emergencies in the absence of effective vaccines. But very few vaccines against these threats have been developed to create proven medical products. The measles vaccine is an efficient, live attenuated, replicating virus that has been safely administered to 2 billion children over the last 40 years, affording life-long protection after a single dose. Taking advantage of these characteristics, this attenuated virus was transformed into a versatile chimeric or recombinant vaccine vector with demonstrated proof-of-principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Clinical trials have shown the safety and immunogenicity of this vaccine platform in individuals with preexisting immunity to measles. This review describes the potential of this platform to develop new vaccines against emerging viral diseases.
Riboflavin is unique among the water-soluble vitamins in that milk and dairy products make the greatest contribution to its intake in Western diets. Meat and fish are also good sources of riboflavin, and certain fruit and vegetables, especially dark-green vegetables, contain reasonably high concentrations. Biochemical signs of depletion arise within only a few days of dietary deprivation. Poor riboflavin status in Western countries seems to be of most concern for the elderly and adolescents, despite the diversity of riboflavin-rich foods available. However, discrepancies between dietary intake data and biochemical data suggest either that requirements are higher than hitherto thought or that biochemical thresholds for deficiency are inappropriate. This article reviews current evidence that diets low in riboflavin present specific health risks. There is reasonably good evidence that poor riboflavin status interferes with iron handling and contributes to the etiology of anemia when iron intakes are low. Various mechanisms for this have been proposed, including effects on the gastrointestinal tract that might compromise the handling of other nutrients. Riboflavin deficiency has been implicated as a risk factor for cancer, although this has not been satisfactorily established in humans. Current interest is focused on the role that riboflavin plays in determining circulating concentrations of homocysteine, a risk factor for cardiovascular disease. Other mechanisms have been proposed for a protective role of riboflavin in ischemia reperfusion injury; this requires further study. Riboflavin deficiency may exert some of its effects by reducing the metabolism of other B vitamins, notably folate and vitamin B-6.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a highly pathogenic respiratory virus with mechanisms that may be driven by innate immune responses. Despite the effort of scientific studies related to this virus, Middle East Respiratory Syndrome (MERS) is still a public health concern. MERS-CoV infection has a high mortality rate, and to date, no therapeutic or vaccine has been discovered, that is effective in treating or preventing the disease. In this review, we summarize our understanding of the molecular and biological events of compounds acting as MERS-CoV inhibitors, the outcomes of existing therapeutic options and the various drugs undergoing clinical trials. Currently, several therapeutic options have been employed, such as convalescent plasma (CP), intravenous immunoglobulin (IVIG), monoclonal antibodies and repurposing of existing clinically approved drugs. However, these therapeutic options have drawbacks, thus the need for an alternative approach. The requirement for effective therapeutic treatment has brought the necessity for additional MERS treatments. We suggest that antimicrobial peptides (AMPs) may be used as alternative therapeutic agents against MERS-CoV infection. In addition, we propose the feasibility of developing effective agents by repurposing the existing and clinically approved anti-coronavirus and anti-viral peptide drugs.
Pathogenic human coronaviruses (CoVs), such as the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome-CoV, cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent Middle East respiratory syndrome outbreak indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection. Our results showed that male mice were more susceptible to SARS-CoV infection compared with age-matched females. The degree of sex bias to SARS-CoV infection increased with advancing age, such that middle-aged mice showed much more pronounced differences compared with young mice. Enhanced susceptibility of male mice to SARS-CoV was associated with elevated virus titers, enhanced vascular leakage, and alveolar edema. These changes were accompanied by increased accumulation of inflammatory monocyte macrophages and neutrophils in the lungs of male mice, and depletion of inflammatory monocyte macrophages partially protected these mice from lethal SARS. Moreover, the sex-specific differences were independent of T and B cell responses. Furthermore, ovariectomy or treating female mice with an estrogen receptor antagonist increased mortality, indicating a protective effect for estrogen receptor signaling in mice infected with SARS-CoV. Together, these data suggest that sex differences in the susceptibility to SARS-CoV in mice parallel those observed in patients and also identify estrogen receptor signaling as critical for protection in females.
In spite of the consistent benefits for HIV-1 infected patients undergoing antiretroviral therapy, a complete immune reconstitution is usually not achieved. Actually, antiretroviral therapy may be frequently accompanied by immunological unresponsiveness, persistent inflammatory conditions and inefficient cytotoxic T-cell response. Thymosin alpha 1 is a thymic peptide that demonstrates a peculiar ability to restore immune system homeostasis in different physiological and pathological conditions (i.e., infections, cancer, immunodeficiency, vaccination and aging) acting as multitasking protein depending on the host state of inflammation or immune dysfunction. This review reports the present knowledge on the in vitro and in vivo studies concerning the use of thymosin alpha 1 in HIV-1 infection. Recent findings and future perspectives of therapeutic intervention are discussed.
Background:
Middle East respiratory syndrome coronavirus (MERS-CoV) has been identified as a potential threat to the safety of blood products. The Mirasol Pathogen Reduction Technology System uses riboflavin and ultraviolet (UV) light to render blood-borne pathogens noninfectious while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against MERS-CoV when tested in human plasma.
Study design and methods:
MERS-CoV (EMC strain) was used to inoculate plasma units that then underwent treatment with riboflavin and UV light. The infectious titers of MERS-CoV in the samples before and after treatment were determined by plaque assay on Vero cells. The treatments were initially performed in triplicate using pooled plasma (n = 3) and then repeated using individual plasma units (n = 6).
Results:
In both studies, riboflavin and UV light reduced the infectious titer of MERS-CoV below the limit of detection. The mean log reductions in the viral titers were ≥4.07 and ≥4.42 for the pooled and individual donor plasma, respectively.
Conclusion:
Riboflavin and UV light effectively reduced the titer of MERS-CoV in human plasma products to below the limit of detection, suggesting that the treatment process may reduce the risk of transfusion transmission of MERS-CoV.
The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo.
Experimental studies of arbidol and arbidol mesylate versus ribavirin suggest that insertion of these agents into the nutrient medium of the cultured cells GMK-AH-1 (D) after infection at concentrations of 50,25, and 100 μg/ml, respectively, is effective in suppressing the reproduction of severe acute respiratory syndrome (SARS) virus. Arbidol and arbidol mesylate were shown to have a direct antiviral effect in early viral replication in the cultured cells. The promising antiviral agent is arbidol mesylate that is nearly 5 times as effective as arbidol in reducing the reproduction of SARS virus in the cultured cells. Insertion of arbidol, arbidol mesylate, and ribavirin into the nutrient medium 2 hours after infection of porcine embryonic renal cells caused a reduction in the accumulation of the pathogen by 2.5, 2.1, and 2.6 Ig, respectively.
Influenza causes an acute infection characterized by virus replication in respiratory epithelial cells. The severity of influenza and other respiratory diseases changes over the life course and during pregnancy in women, suggesting that sex steroid hormones, such as estrogens, may be involved. Using primary, differentiated human nasal epithelial cell (hNEC) cultures from adult male and female donors, we exposed cultures to the endogenous 17β-estradiol (E2) or select estrogen receptor modulators (SERMs), then infected cultures with a seasonal influenza A virus (IAV) to determine whether estrogenic signaling could affect the outcome of IAV infection and whether these effects where sex-dependent. Estradiol, raloxifene, and bisphenol A decreased IAV titers in hNECs from female, but not male, donors. The estrogenic decrease in viral titer was dependent on the genomic estrogen receptor- 2 (ESR2) as neither genomic ESR1 nor non-genomic GPR30 were expressed in hNEC cultures and addition of the genomic ER antagonist ICI 182,780 reversed the antiviral effects of E2. Treatment of hNECs with E2 had no effect on interferon or chemokine secretion, but significantly downregulated cell metabolic processes, including genes that encode for zinc finger proteins, many of which contain estrogen response elements in their promoters. These data provide novel insights into the cellular and molecular mechanisms of how natural and synthetic estrogens impact IAV infection in respiratory epithelial cells derived from humans.
As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization—International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).
Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel single-stranded, positive-sense RNA betacoronavirus (MERS-CoV). Dromedary camels, hosts for MERS-CoV, are implicated in direct or indirect transmission to human beings, although the exact mode of transmission is unknown. The virus was first isolated from a patient who died from a severe respiratory illness in June, 2012, in Jeddah, Saudi Arabia. As of May 31, 2015, 1180 laboratory-confirmed cases (483 deaths; 40% mortality) have been reported to WHO. Both community-acquired and hospital-acquired cases have been reported with little human-to-human transmission reported in the community. Although most cases of MERS have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported in Europe, the USA, and Asia in people who travelled from the Middle East or their contacts. Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities. No specific drug treatment exists for MERS and infection prevention and control measures are crucial to prevent spread in health-care facilities. MERS-CoV continues to be an endemic, low-level public health threat. However, the virus could mutate to have increased interhuman transmissibility, increasing its pandemic potential.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Background: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. Methods: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. Results: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 µg/ml and 50 µg/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls—both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)—but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. Conclusions: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.