Vitamin A Deficiency, COVID-19, and Rhino-Orbital Mucormycosis (Black Fungus): An Analytical Perspective.

Mucormycosis is a rare but serious opportunistic fungal disease characterized by rhino-orbito-cerebral and pulmonary involvement. It is mainly seen in people with secondary immunosuppression, isolated vitamin A deficiency, measles, and AIDS patients. It showed a rise during the second wave of the COVID-19 epidemic in the spring of 2021 in India, especially in diabetic COVID-19 patients. Vitamin A deficiency is known to cause nutritional immunodeficiency and hence leading the way to increased opportunistic fungal, bacterial, and viral infections. In the eye, it causes keratitis, night blindness, xerophthalmia, conjunctivitis, Bitot spots, keratomalacia, and retinopathy. It also causes decreased tear secretion and deterioration of the anatomical/physiological defense barrier of the eye. The negative impact of vitamin A deficiency has been previously demonstrated in measles, AIDS, and COVID-19. We think that mucormycosis in COVID-19 might be rendered by vitamin A deficiency and that vitamin A supplementation may have preventive and therapeutic values against mucormycosis and other ocular symptoms associated with COVID-19. However, any vitamin A treatment regimen needs to be based on laboratory and clinical data and supervised by medical professionals.

Study of the Relationships between COVID-19, Associated Diseases, and Vitamins

Background: Some vitamins play a beneficial role in the immune system and certain diseases may be associated with an increase in the number of COVID-19 cases and mortality. Objective(s): In this work, we aim to verify a possible relationship between vitamin A, vitamin D, sunlight, and COVID-19 cases and mortality. We also aim to study the relationship between chronic diseases and COVID-19 in the world. Method(s): We consulted online databases (Johns Hopkins, World Life Expectancy, NASA, and World Health Organization) and used SPSS (v23) for statistical analysis. Result(s): We found that countries with the highest number of cases and deaths by COVID-19 are the countries with the highest death rates from different types of cancer and multiple sclerosis. Besides, the relationship between cancer death rate and COVID-19 is not biased by the life expectancy. We also found that the low solar incidence and low vitamins A and D levels can be related to the number of cases and deaths by COVID-19. Conclusion(s): Our findings suggest a relationship between different cancer types and multiple sclerosis death rates and COVID-19. We also recommend that vitamins D and A may play a protective role in COVID-19 infection.Copyright © 2021 Bentham Science Publishers.

Evaluation of COVID-19 risk in patients on systemic retinoid therapy

Background and Design: Systemic retinoids are commonly used medications in dermatology and indicated in various skin disorders such as acne vulgaris and psoriasis. Data about the risk of Coronavirus disease-2019 (COVID-19) in patients using systemic retinoids are limited. Thus, this study aimed to investigate the risk of COVID-19 in patients undergoing systemic retinoid therapy. Materials and Methods: A total of 186 patients who have undergone systemic isotretinoin and acitretin therapy were recruited. Patients who presented to the dermatology clinic for various skin diseases, such as eczema, vitiligo, tinea, etc., who were not on systemic retinoid therapy, and who received topical medications comprised the control group. The development of COVID-19 in the retinoid therapy group and the control group was retrospectively reviewed using hospital database. Results: The mean age of the patients in the retinoid therapy group was 25.72+or-0.67 and that in the control group was 25.4+or-0.62. Moreover,165 patients received isotretinoin, and 21 patients received acitretin treatment. The isotretinoin dosage ranged from 0.5 to 0.8 mg/kg wheras the acitretin dosage ranged between 10 and 25 mg/day. Two patients (1.07%) in the retinoid therapy group and 8 (4.3%) patients in the control group were diagnosed with COVID-19. None of the patients receiving acitretin was diagnosed with COVID-19. COVID-19 diagnosis was established in the 2nd and 3rd months of isotretinoin treatment, and lung involvement was not observed. No significant difference regarding the number of COVID-19 cases and disease severity was found between the two groups (p=0.105;p=0.258, respectively). Conclusion: Isotretinoin and acitretin use was not associated with increased COVID-19 risk or disease severity. Systemic retinoids appear to be a safe treatment modality in the COVID-19 era.

The multiphasic TNF-α-induced compromise of Calu-3 airway epithelial barrier function.

Purpose: Airway epithelial barrier leak and the involvement of proinflammatory cytokines play a key role in a variety of diseases. This study evaluates barrier compromise by the inflammatory mediator Tumor Necrosis Factor-α (TNF-α) in the human airway epithelial Calu-3 model. Methods: We examined the effects of TNF-α on barrier function in Calu-3 cell layers using Transepithelial Electrical Resistance (TER) and transepithelial diffusion of radiolabeled probe molecules. Western immunoblot analyses of tight junctional (TJ) proteins in detergent soluble fractions were performed. Results: TNF-α dramatically reduced TER and increased paracellular permeability of both 14C-D-mannitol and the larger 5 kDa probe, 14C-inulin. A time course of the effects shows two separate actions on barrier function. An initial compromise of barrier function occurs 2-4 hours after TNF-α exposure, followed by complete recovery of barrier function by 24 hrs. Beginning 48 hrs. post-exposure, a second more sustained barrier compromise ensues, in which leakiness persists through 144 hrs. There were no changes in TJ proteins observed at 3 hrs. post exposure, but significant increases in claudins-2, -3, -4, and -5, as well as a decrease in occludin were seen at 72 hrs. post TNF-α exposure. Both the 2-4 hr. and the 72 hr. TNF-α induced leaks are shown to be mediated by the ERK signaling pathway. Conclusion: TNF-α induced a multiphasic transepithelial leak in Calu-3 cell layers that was shown to be ERK mediated, as well as involve changes in the TJ complex. The micronutrients, retinoic acid and calcitriol, were effective at reducing this barrier compromise caused by TNF-α. The significance of these results for airway disease and for COVID-19 specifically are discussed.

Effect of nutrition awareness on utilization of Orange Fleshed Sweetpotato among vulnerable populations in Kenya.

Malnutrition continues to affect many vulnerable populations worldwide, with the majority of these residing in developing and underdeveloped countries. This problem has been exacerbated by the changing climate and more recently by the COVID-19 pandemic. Urgent efforts geared towards enhancing sustainable production and value chains of nutritious foods to ensure access to healthier diets are therefore critical. A recent partnership between the World Food Programme and the International Potato Center to enhance utilization of biofortified crops in fragile environments in Kenya is a step in this direction, aimed at improving the diets of households at risk of hunger and malnutrition. This study sets out to provide early evidence on the potential impacts of the interventions spearheaded in this partnership, together with lessons for further scaling efforts. Using household level data, the study adopts an impact evaluation framework to understand the effect of nutrition awareness through the dissemination of information on Vitamin A deficiency, on the utilization of orange fleshed sweetpotato, a biofortified crop rich in Vitamin A. Results show positive and significant effects of nutrition awareness on utilization of the orange-fleshed sweetpotato. Several factors were also identified as key to determining the exposure to nutrition awareness, including proximity to markets and extension agents, gender, and education levels. For widespread and inclusive adoption and utilization of orange-fleshed sweetpotato, out-scaling efforts need to consider these determinants in designing interventions aimed at raising nutrition awareness, as a key entry point to enhancing utilization of orange-fleshed sweetpotato.

Update on "Treatment of orthostatic headache without intracranial hypotension: A case report" - nine years later.

BACKGROUND: In 2013, one of the authors described a 36-year-old female with orthostatic headache without documented intracranial hypotension or evidence of cerebrospinal fluid leak, despite extensive workup. Headache was unresponsive to conservative treatment since 2010, showed only transient benefit after repeated epidural blood patches while vitamin A supplementation resulted in progressive improvement. CASE: Since 2013, the patient followed a relapsing and remitting course yet relapse control became difficult after a drug induced liver injury required vitamin A discontinuation in 2017, when her headache became chronic. Greater occipital nerve blocks provided pain relief as alternative but were stopped due to the pandemic and her latest severe relapse, in late 2020, required not only restarting anaesthetic blocks and aggressive medication management, but also reassessing and treating comorbidities (obstructive sleep apnoea and major depressive disorder) with modest benefit. CONCLUSION: Orthostatic headache without intracranial hypotension is rare, with only 28 cases reported so far, all treated empirically and all treatment options revealing to be mostly ineffective. Vitamin A anecdotally appeared to be useful in our case but had to be stopped for severe side effects, so unfavourable long-term prognosis, in ours and 2/3 of the reported cases, seems to be the rule in this intriguing entity.

Evaluation and comparison of vitamin A supplementation with standard therapies in the treatment of patients with COVID-19.

Background: Incomplete data are often presented for determining the role of vitamin A supplement therapy for improving treatment outcomes in patients with COVID-19. Aims: We compared treatment effects between a group that received vitamin A added to the standard COVID-19 treatment and another group that received the standard drug treatment alone. Methods: Participants in this triple-blind controlled trial comprised 182 COVID-19 outpatients in Saveh City, Markazi Province, Islamic Republic of Iran, in 2020. Patients were randomly divided into experimental (n = 91) and control (n = 91) groups. Patients in the control group received the national standard treatment for COVID-19 (hydroxychloroquine), and those in the intervention group received 25 000 IU/d oral vitamin A for 10 days in addition to the standard treatment recommended by the national protocol. We evaluated the clinical symptoms, paraclinical criteria, and hospitalization status before and after 10 days of interventions. Results: The treatment groups did not differ significantly in clinical and paraclinical symptoms before the intervention. However, clinical symptoms such as fever, body ache, weakness and fatigue, paraclinical symptoms, white blood cell count, and C-reactive protein showed significantly greater decreases in the experimental group 10 days post-intervention compared with the standard treatment alone (P < 0.05). Conclusion: Vitamin A supplementation demonstrated efficacy in improving some clinical and paraclinical symptoms in patients with COVID-19. Future studies should evaluate vitamin A supplementation with a larger sample size and compare different dosages, especially in hospitalized patients.

Role of Vitamin A Supplementation in Prevention and Control of Coronavirus Disease-19: A Narrative Review.

Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 is a novel viral infectious disease, which broke out in the end of winter season 2019 in China and soon became a pandemic. Characteristically there was severe local and systemic immune-inflammatory response to the virus, damaging the respiratory system and other organ systems. The morbidity and mortality caused by the disease are producing tremendous impact on health. The understanding about pathogenesis and manifestations of the disease was obscure. To date, no classic treatment or preventive measure was available for COVID-19 other than symptomatic and supportive care or few drugs under trial. A possibility exists that maintaining vitamin A adequate levels can protect the affected respiratory mucosa, increase antimicrobial activity, produce better antibody response, and have antiinflammatory effects, thereby promoting repair and healing as well. It has been discussed in the review that by various mechanisms, immune regulation through vitamin A supplementation is beneficial to boost immunity in the current outbreak situation when the population is susceptible to the disease. There is a high possibility that vitamin A supplementation to cases as well as population at risk of COVID-19 has a key role in prevention and control. Hence, it is believed that along with other therapeutic and preventive measures, maintaining vitamin A sufficiency during and prior to the development of active disease may act as an adjuvant in population at risk and cases to prevent and control COVID-19.

Effect of vitamin A supplementation on the outcome severity of COVID-19 in hospitalized patients: A pilot randomized clinical trial.

INTRODUCTION: Vitamin A is one of the vitamins that is suggested as adjuvant therapy in viral infections due to its immune enhancing role. In the present clinical trial, we intended to assess the effect of vitamin A supplementation on Coronavirus disease-2019 (COVID-19) in hospitalized patients. METHODS: The present pilot randomized controlled clinical trial was conducted on 30 hospitalized patients with COVID-19. Patients in the intervention group received 50000 IU/day intramuscular vitamin A for a maximum of two weeks. Patients in the control group continued their common treatment protocols. All participants were followed up until discharge from the hospital or death. The primary outcome of the study was time to achieve clinical response based on the six classes of an ordinal scale. Time to clinical response was calculated based on the days needed to improve two scores on the scale or patient's discharge. RESULTS: The time to clinical response was not significantly different between the two groups (7.23 ± 2.14 vs. 6.75 ± 1.85 days, respectively, p = 0.48). There was no significant difference between the groups regarding clinical response (hazard ratio: 1.76 [95% CI: 0.73, 4.26]). There were no significant differences between groups regarding the need for mechanical ventilation, duration of hospitalization, or death in the hospital. CONCLUSION: The results of this pilot clinical trial showed no benefit of vitamin A compared with the common treatment on outcome severity in hospitalized patients with COVID-19. Although the results are negative, there is still a great need for future clinical studies to provide a higher level of evidence.

Serum Vitamins A, D, and Zinc Levels in Children with Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children

Objective Vitamin D, due to its immunomodulating effect, zinc, and vitamin A, which affect cellular and humoral immunity, are thought to affect the clinical severity of coronavirus disease 2019 (COVID-19) infection. The present study evaluates the association between vitamin A, D, and zinc deficiencies and disease severity in pediatric patients with COVID-19 infections. Methods The levels of vitamin A, D, and zinc at the time of diagnosis of 123 pediatric patients who presented to our hospital and were diagnosed as having hospitalized, nonhospitalized COVID-19 infection group, and multisystem inflammatory syndrome in children (MIS-C) were evaluated. The correlations of the measured levels with the disease severity and the need for intensive care or hospitalization were analyzed. Results Among the 123 patients, 21.1% (n = 26), 42.2% (n = 52), and 36.7% (n = 45) had a diagnosis of MIS-C, belonged to the hospitalized COVID-19 infection group, or belonged to the nonhospitalized COVID-19 infection group, respectively. Zinc levels were significantly lower in the MIS-C group than in the nonhospitalized group (p < 0.05). Vitamin A levels were found to be significantly lower in the MIS-C group than in the nonhospitalized group (p < 0.01) and significantly lower in the hospitalized group when compared with the nonhospitalized group (p < 0.001). Deficiencies in vitamin A, vitamin D, and zinc levels were found to be most common in the MIS-C group (42.3%) and in hospitalized COVID-19 group (15.3%). In the nonhospitalized COVID-19 group, it was found to be the lowest at 6.6%. Conclusion Based on the results of the present study and a literature review, it can be said that vitamin A, D, and zinc deficiencies may associate with the severity of COVID-19, although more studies are required to clarify this subject further.

Can vitamin D protect against covid-19?

Two new trials find no effect, but aren’t the final word

Investigational drugs for the treatment of olfactory dysfunction.

INTRODUCTION: Olfactory dysfunction could be the sign of acquired or degenerative diseases. The loss of the sense can be caused by a damage in the nasal structure (olfactory epithelium) or a neuro inflammation/degeneration in the superior olfactory pathway. The understanding of the origin of the smell alteration would be desirable for appropriate management of the problem. Unfortunately, clinical investigations do not always allow to define the exact cause. AREAS COVERED: This review discusses the treatments available and their mechanism of action based on the administration methods; in fact, just looking at the results obtained by the researcher using topic versus systemic treatment, might be possible to speculate about the peripheral or central origin of the olfactory disorder. EXPERT OPINION: Because COVID-19 causes olfactory loss and several treatments (topical and systemic) have been tested in this disease, we have decided to use this model of acquired olfactory loss to discuss the different therapeutical option. The authors believe these treatments might be an option also for treating olfactory disease related to neurodegeneration.

Retinol Depletion in COVID-19.

Background and aims: COVID-19 has been a devastating pandemic. There are indications that vitamin A is depleted during infections. Vitamin A is important in development and immune homeostasis. It has been used successfully in measles, RSV and AIDS infections. In this study, we aimed to measure the serum retinol levels in severe COVID-19 patients to assess the importance of vitamin A in the COVID-19 pathogenesis. Methods: The serum retinol level was measured in two groups of patients: the COVID-19 group, which consisted of 27 severe COVID-19 patients hospitalized in the intensive care unit with respiratory failure, and the control group, which consisted of 23 patients without COVID-19 symptoms. Results: The mean serum retinol levels were 0.37 mg/L in the COVID-19 group and 0.52 mg/L in the control group. The difference between the serum retinol levels in the two groups was statistically significant. There was no significant difference in retinol levels between different ages and genders within the COVID-19 group. Comorbidity did not affect serum retinol levels. Conclusion: The serum retinol level was significantly lower in patients with severe COVID-19, and this difference was independent of age or underlying comorbidity. Our data show that retinol and retinoic acid signaling might be important in immunopathogenesis of COVID-19.

Significantly Reduced Retinol Binding Protein 4 (RBP4) Levels in Critically Ill COVID-19 Patients.

The SARS-CoV-2 virus is the causative agent of the COVID-19 pandemic. The disease causes respiratory failure in some individuals accompanied by marked hyperinflammation. Vitamin A (syn. retinol) can exist in the body in the storage form as retinyl ester, or in the transcriptionally active form as retinoic acid. The main function of retinol binding protein 4 (RBP4), synthesized in the liver, is to transport hydrophobic vitamin A to various tissues. Vitamin A has an important role in the innate and acquired immune system. In particular, it is involved in the repair of lung tissue after infections. In viral respiratory diseases such as influenza pneumonia, vitamin A supplementation has been shown to reduce mortality in animal models. In critically ill COVID-19 patients, a significant decrease in plasma vitamin A levels and an association with increased mortality have been observed. However, there is no evidence on RBP4 in relation to COVID-19. This prospective, multicenter, observational, cross-sectional study examined RBP4 (enzyme-linked immunosorbent assay) and vitamin A plasma levels (high-performance liquid chromatography) in COVID-19 patients, including 59 hospitalized patients. Of these, 19 developed critical illness (ARDS/ECMO), 20 developed severe illness (oxygenation disorder), and 20 developed moderate illness (no oxygenation disorder). Twenty age-matched convalescent patients following SARS-CoV-2 infection, were used as a control group. Reduced RBP4 plasma levels significantly correlated with impaired liver function and elevated inflammatory markers (CRP, lymphocytopenia). RBP4 levels were decreased in hospitalized patients with critical illness compared to nonpatients (p < 0.01). In comparison, significantly lower vitamin A levels were detected in hospitalized patients regardless of disease severity. Overall, we conclude that RBP4 plasma levels are significantly reduced in critically ill COVID-19 patients during acute inflammation, and vitamin A levels are significantly reduced in patients with moderate/severe/critical illness during the acute phase of illness.

General overview on SARS-CoV-2 and potential role of natural compounds as antiviral drugs targeting SARS-CoV-2 proteins. (Special issue.)

Purpose: The novel coronavirus disease namely COVID-19 is a viral disease induced by severe acute respiratory syndrome coronavirus (SARS-CoV-2). The cases were first reported in Wuhan, China, by the end of 2019 and subsequently spread worldwide. The virus can be transferred through direct or indirect contact and leads to several manifestations;the most common are fever, dry cough, pneumonia, and acute respiratory distress syndrome (ARDS). COVID-19 has caused massive human and economic losses, posing an ongoing threat. Understanding the current situation and developing a treatment which can be both safe and effective has become essential. In this regard, natural products could be an important resource in the development of treatment for COVID-19, as they have contributed to the treatment of other viruses in the past. This review aims to understand the cellular machinery of SARS-CoV-2 and to identify its drug targets.

Boosting the immune system with functional compounds during the COVID-19 pandemic: a review

Background: More than 1 year has passed since the outbreak of the COVID-19 pandemic. Nutrition and its role in boosting the immune system have been a hot topic during the previous year in the light of the COVID-19 pandemic. An effective medicine for COVID-19 has not been introduced and public vaccination has not gained an acceptable speed in the world;therefore, preventive measures, protocols adherence, and a robust immune system are crucial. The aim of this study was to evaluate the role of food in boosting the immune system during the Covid-19 pandemic.

Determinants of Household Nutrition Security in Countries in Protracted Crisis: Evidence from South Sudan

Undernutrition is a considerable challenge in sub-Saharan Africa, especially in countries affected by a protracted crisis, but the literature lacks information on the underlying mechanisms influencing micro- and macronutrients, and appropriate analytical tools are needed to assist policymakers and implementers. The paper contributes to filling this gap, focusing on the Western Bahr el Ghazal state in South Sudan and using primary data collected in May–June 2019 for a statistically representative sample of households. The literature typically uses one micro- or macronutrient as a proxy of nutritional status. On the contrary, the study applied a MANCOVA with an artificial dependent variable, including protein, vitamin A, and heme iron, in a single experiment to discover the variables that better explain household nutritional status. Dietary diversity explains the largest proportion of variance in household nutritional status. The importance of the variables in explaining the variance in the specific micro- and macronutrients depends on the explanatory variable. Therefore, the results suggest the possible misinterpretation of undernutrition using one nutrient. Moreover, they highlight the importance of a multisectoral approach to the problem with a central role played by agriculture and the urgency of the reinforcement of the humanitarian–development–peace nexus to improve household nutrition security in South Sudan.

Herbal plants: an alternative therapy to combat immunity disorders & COVID-19

COVID-19, a worldwide epidemic, is afflicting the whole planet. Vaccines have been developed;however, they will not be able to eliminate the COVID-19 virus. As a result, the only approach to address the problem is to the disease is to have a robust immune system. A well-balanced diet can help enhance immunity, which is necessary for preventing and treating viral illnesses. Vitamins A, C, and D and minerals like Selenium and Zinc found in fruits, herbs, and vegetables have been demonstrated to have beneficial immunity-enhancing effects in viral respiratory infections. In this publication, we have attempted to describe the advantages of medicinal herbs, vitamins, minerals, nutraceuticals, and probiotics in combating the new Coronavirus. The dietary concept based on existing evidence might help inhibit and regulate COVID-19.

Vitamin A and viral infection in critical care

Vitamin A is fat-soluble compounds of retinoid derivate, consisting of retinol, retinal, and retinyl esters. Vitamin A also affects cell growth and differentiation, playing a critical role in the normal formation and function of the heart, lungs, kidneys, and other organs. According to the role of vitamin A in enhancing immune function, it is known as an anti-inflammatory agent. Also, vitamin A supplementation by reducing morbidity and mortality in different infectious diseases, such as measles, diarrheal disease, measles-related pneumonia, human immunodeficiency virus infection, and malaria considered as a crucial factor against infection. So vitamin A deficiency can be life-threatening, because of impairing the response to infection and significant risk of development of severe respiratory infections in infants and young children. In this paper, we have discussed the effects of vitamin A in modulating immune responses in viral infections and the direct effects of this vitamin on viral replication by comparing its role during different types of viral infections.

Machine Learning Method to Discover the Novel Association of Vaccine and Vitamin A Supplement on Covid 19 Infection: A Biclustering Approach

This article attempts to discover the novel association of vaccines (administered for other diseases) and vitamin A supplement coverage across different countries and the spread of COVID-19.This relation may be affected by several unknown factors as the disease spreads over regions with diverse economic, cultural and climatic conditions. In this situation, relevant associations between features may exist for a subset of countries rather than the entire set of countries.We use a machine learning method named RelDenClu to identify the effects of vaccines or vitamin supplements on the spread of COVID-19. RelDenClu is a non-linear relation based biclustering technique. From the experiment, it was found that countries providing the Tetanus-Toxoid vaccine have lower COVID-19 infection rates. The performance of the proposed technique is also compared with decision tree, LASSO and CBSC and it is noticed that all these methods discover the same association (i.e., countries with a higher rate of administering Tetanus-Toxoid vaccine show lower COVID-19 infection). However, the proposed method can discover the said association in less computation time. Additionally, the proposed method is general enough to be applied to other datasets for finding associations between different local factors affecting the proliferation of any disease across different regions. © 2021 IEEE.