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Effects of probiotic administration on overweight or obese children: a meta-analysis and systematic review.
Li, Y, Liu, T, Qin, L, Wu, L
Journal of translational medicine. 2023;21(1):525
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The prevalence of overweight or obesity in children is increasing due to changes in dietary structure and exercise habits, as determined by the body mass index (BMI) calculated from height and weight. Childhood obesity can cause some clinical complications such as hypertension, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. The aim of this study was to examine the effects of probiotics on eight factors in children with overweight or obesity. This study was a systematic review and meta-analysis of four studies with a total of 206 overweight or obesity children. Among them, 105 were in the probiotic group, and 101 were in the placebo group. Results showed that probiotics can improve high- and low-density lipoprotein cholesterol, adiponectin, leptin, and TNF-α in overweight or obese children. The systematic review showed that probiotics work mainly by reshaping disturbed intestinal microbiota, regulating lipid metabolism, reducing inflammation and immune response, playing a positive effect of short-chain fatty acids produced, alleviating oxidative stress and endoplasmic reticulum stress, and inhibiting the growth and reproduction of pathogens in the gut. Authors concluded that probiotics could regulate lipid metabolism and immune response to some degree in children with overweight or obesity.
Abstract
BACKGROUND This paper aimed to examine the effects of probiotics on eight factors in overweight or obese children by meta-analysis, namely, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adiponectin, leptin and tumor necrosis factor-α (TNF-α) and summarize the mechanisms of action of probiotics based on the existing researches. METHODS Six databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed and CNKI) were searched until March 2023. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model or random effect model to observe the effects of probiotic administration on the included indicators. RESULTS Four publications with a total of 206 overweight or obesity children were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HDL-C (MD, 0.06; 95% CI 0.03, 0.09; P = 0.0001), LDL-C (MD, - 0.06; 95% CI - 0.12, - 0.00; P = 0.04), adiponectin (MD, 1.39; 95% CI 1.19, 1.59; P < 0.00001), leptin (MD, - 2.72; 95% CI - 2.9, - 2.54; P < 0.00001) and TNF-α (MD, - 4.91; 95% CI - 7.15, - 2.67; P < 0.0001) compared to those in the placebo group. Still, for BMI, the palcebo group seemed to be better than the probiotic group (MD, 0.85; 95% CI 0.04, 1.66; P = 0.04). TC (MD, - 0.05; 95% CI - 0.12, 0.02; P = 0.14) and TG (MD, - 0.16; 95% CI - 0.36, 0.05; P = 0.14) were not different between two groups. CONCLUSIONS This review drew that probiotics might act as a role in regulating HDL-C, LDL-C, adiponectin, leptin and TNF-α in overweight or obesity children. Additionally, our systematic review yielded that probiotics might regulate lipid metabolism and improve obese associated symptoms by some paths. This meta-analysis has been registered at PROSPERO with ID: CRD42023408359.
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A randomized trial of probiotic supplementation in nurses to reduce stress and viral illness.
Slykerman, RF, Li, E
Scientific reports. 2022;12(1):14742
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Dynamic communication occurs between the gut microbiota and the central nervous system along multiple physiological pathways. Stress increases glucocorticoid production and activation of the hypothalamic–pituitary–adrenal axis, affecting immunological function and neuronal changes. The aim of this study was to investigate whether supplementation with the probiotic Lactobacillus rhamnosus HN001 could reduce symptoms of stress and anxiety and improve psychological wellbeing in nurses working during the COVID19 pandemic. This study was a large double-blind, placebo-controlled randomised trial of probiotic supplementation with two parallel arms and a ratio of allocation to probiotic or placebo of 1:1. Results showed that following the intervention, stress, anxiety, and psychological wellbeing were not significantly different between nurses supplemented with the probiotic and those who received the placebo. Furthermore, the average number of days per week that nurses reported symptoms of cold or flu-like illness did not significantly differ between the probiotic and placebo supplemented groups. Authors conclude that there weren’t significant differences in outcomes between the probiotic and placebo groups.
Abstract
Animal studies demonstrate how the gut microbiota influence psychological health and immunity to viral infections through their actions along multiple dynamic pathways in the body. Considerable interest exists in probiotics to reduce stress and illness symptoms through beneficial effects in the gut, but translating pre-clinical evidence from animal models into humans remains challenging. We conducted a large trial in nurses working during the 2020 COVID19 pandemic year to establish whether daily ingestion of the probiotic Lactobacillus rhamnosus HN001 reduced perceived stress and the number of days participants reported symptoms of a viral illness. Our results showed no significant difference in perceived stress or the average number of illness days between probiotic supplemented nurses and the placebo group. Stress and viral illness symptoms reduced during the study for all participants, a trajectory likely influenced by societal-level factors. The powerful effect of a well-managed public health response to the COVID19 pandemic and the elimination of COVID19 from the community in 2020 may have altered the trajectory of stress levels and reduced circulating viral infections making it difficult to detect any effect of probiotic supplementation. Our study highlights the challenge in controlling environmental factors in human trials.
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The role of probiotics in the treatment of adult atopic dermatitis: a meta-analysis of randomized controlled trials.
Umborowati, MA, Damayanti, D, Anggraeni, S, Endaryanto, A, Surono, IS, Effendy, I, Prakoeswa, CRS
Journal of health, population, and nutrition. 2022;41(1):37
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Allergic diseases, including atopic dermatitis (AD), are serious conditions that disrupt the quality of life of affected individuals. AD is a chronic inflammatory skin disease that is relapsing and whose onset is generally related to a patient’s or family’s atopic history such as asthma and allergic rhinitis. The aim of this study was to assess randomized control trials based on the PICO strategy—population = adult with AD; intervention = probiotic intervention; control = standard therapy; and outcome = clinical manifestations (Scoring Atopic Dermatitis index (SCORAD) evaluation, skin severity, itch severity), quality of life, and/or immune response. This study is a systematic review of six randomised controlled trials involving a total of 241 subjects, including 128 subjects in the probiotics group and 113 subjects in the placebo group. Results show that probiotic supplementation may have the potential to decrease disease severity (SCORAD) in adult AD. Therefore, decrease in disease severity may also improve the quality of life. Authors conclude that based on their findings, probiotics can be used as adjuvant treatment of adult AD.
Abstract
BACKGROUND Atopic dermatitis (AD) is chronic inflammatory skin disease that is relapsing and a serious condition that disrupts the quality of life of affected individuals. Probiotics are an immunomodulator that can enhance the immune control of atopic dermatitis. METHODS All randomized controlled trials of probiotics for the treatment of adult AD published before December 2020 were included in this study from the PubMed databases and manual searching. RESULTS Six randomized controlled trials (n = 241) were selected for this meta-analysis study. Probiotics were effective in treating adult patients with AD, indicated by the decrease in Scoring Atopic Dermatitis/SCORAD (Mean Difference (MD) - 7.90, 95% CI - 7.25 to - 6.92; p < 0.00001; I2 = 96%) and improved quality of life (MD - 7.68, 95% CI - 14.08 to - 1.29; p = 0.02; I2 = 47%) which were statistically significant. However, skin severity, itch severity, Dermatology Life Quality Index (DLQI), IL-4, TFN-γ, and IgE showed no significant difference in this meta-analysis study (p > 0.05). LIMITATIONS The study found no available data for side effects of probiotics. STRENGTH This meta-analysis analyzed a total of 241 AD patients of Asian and European origin. CONCLUSION The use of probiotics decreased SCORAD significantly in adult patients with AD. Probiotics can improve the quality of life of patients with AD. The use of probiotics in atopic dermatitis has been widely studied, with controversial results. This meta-analysis suggests that the use of probiotics can improve SCORAD and the quality of life of patients with atopic dermatitis.
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The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis.
Luo, C, Peng, S, Li, M, Ao, X, Liu, Z
Frontiers in immunology. 2022;13:848279
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Allergic rhinitis (AR) is characterized by a nasal sensitive inflammation. Common symptoms of AR are nasal itching, sneezing, rhinorrhoea, and nasal congestion. In addition, some patients experience symptoms of allergic rhinoconjunctivitis, such as watery or itchy or red eyes. The aim of this study was to address the effect and safety of probiotics on AR and to explore the possible causes of between-study heterogeneity via subgroup. This study is a systematic review and meta-analysis of twenty-eight randomised controlled trials. Results showed that probiotics supplementation for patients with AR can ameliorate AR symptoms and improve the quality of life. Probiotics supplementation can correct the T helper cell 1/ T helper cell 2 balance. Furthermore, there was no significant change in overall or antigen-specific immunoglobulin E levels between probiotic-treated and placebo-treated subjects. Authors conclude that in spite of the positive results of some outcomes, there is weak evidence that probiotics have a potential benefit in the treatment of AR.
Abstract
Background: Probiotics have proven beneficial in a number of immune-mediated and allergic diseases. Several human studies have evaluated the efficacy and safety of probiotics in allergic rhinitis; however, evidence for their use has yet to be firmly established. Objective: We undertook a systematic review and meta-analysis aiming to address the effect and safety of probiotics on allergic rhinitis. Methods: We systematically searched databases [MEDLINE (PubMed), Embase, and the Cochrane Central Register of Controlled Trials] from inception until June 1, 2021. Qualified literature was selected according to inclusion and exclusion criteria, the data were extracted, and a systematic review and meta-analysis was conducted. Results: Twenty-eight studies were included. The results showed that probiotics significantly relieved allergic rhinitis symptoms (standardized mean difference [SMD], -0.29, 95% confidence interval (CI) [-0.44, -0.13]; p = 0.0003, I 2 = 89%), decreased Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores compared with the control group (SMD, -0.64, 95% CI [-0.79, -0.49], p < 0.00001, I 2 = 97%), and increased T helper cell 1(Th1)/Th2 ratio (mean difference [MD], -2.47, 95% CI [-3.27, -1.68], p < 0.00001, I 2 = 72%). There was no significant change in overall or specific IgE levels between probiotic-treated and placebo-treated subjects (SMD, 0.09, 95% CI [-0.16, 0.34], I 2 = 0%, and SMD, -0.03, 95% CI [-0.18, 0.13], p = 0.72, I 2 = 0%, respectively). Conclusions: To sum up, probiotic supplement seems to be effective in ameliorating allergic rhinitis symptoms and improving the quality of life, but there is high heterogeneity in some results after subgroup analysis and clinicians should be cautious when recommending probiotics in treating allergic rhinitis. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO (CRD42021242645).
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Western Dietary Pattern Antioxidant Intakes and Oxidative Stress: Importance During the SARS-CoV-2/COVID-19 Pandemic.
Trujillo-Mayol, I, Guerra-Valle, M, Casas-Forero, N, Sobral, MMC, Viegas, O, Alarcón-Enos, J, Ferreira, IM, Pinho, O
Advances in nutrition (Bethesda, Md.). 2021;12(3):670-681
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The Atlantic diet (AD), Mediterranean diet (MD) and diets which follow the American dietary guidelines (AmD) all supply enough nutrients for the body to stay healthy. However, during periods of viral pandemics, such as the Covid-19 pandemic, these diets may be inadequate for optimal resistance to infection. Furthermore, nutrient requirements may alter with age, stress, and health. This review paper aimed to discuss the three different diets and their suitability depending on age and physical and mental state. Supplementation during a pandemic was also discussed. When the body contracts viruses such as Covid-19, reactive oxygen species can accumulate resulting in oxidative stress which can damage the cells. Nutrients in the diet, which act as antioxidants may be of benefit, in this instance, however traditional balanced diets such as the AD, MD and AmD may be inadequate. In tandem with a balanced diet, supplementation may improve health. Zinc, vitamin A, selenium, vitamin D, vitamin C, and iron have been shown in research to improve the body’s response to viruses. It was concluded that the Covid-19 pandemic has caused severe infections, which can result in oxidative stress, increasing vulnerability to viral infections. Supplementing certain nutrients may be of benefit especially in vulnerable individuals. This study could be used by healthcare professionals to understand that a balanced diet is essential during viral pandemics, and it may be necessary to consider supplementation for high-risk individuals.
Abstract
The importance of balanced dietary habits, which include appropriate amounts of antioxidants to maintain the immune system, has become increasingly relevant during the current SARS-CoV-2/COVID-19 pandemic, because viral infections are characterized by high oxidative stress. Furthermore, the measures taken by governments to control the pandemic have led to increased anxiety, stress, and depression, which affect physical and mental health, all of which are influenced by nutritional status, diet, and lifestyle. The Mediterranean diet (MD), Atlantic diet (AD), and the Dietary Guidelines for Americans all provide the essential vitamins, minerals, and phenolic compounds needed to activate enzymatic and nonenzymatic antioxidant responses. However, viral pandemics such as the current COVID-19 crisis entail high oxidative damage caused by both the infection and the resultant social stresses within populations, which increases the probability and severity of infection. Balanced dietary patterns such as the MD and the AD are characterized by the consumption of fruit, vegetables, legumes, olive oil, and whole grains with low intakes of processed foods and red meat. For a healthy lifestyle in young adults, the MD in particular provides the required amount of antioxidants per day for vitamins D (0.3-3.8 μg), E (17.0 mg), C (137.2-269.8 mg), A (1273.3 μg), B-12 (1.5-2.0 μg), and folate (455.1-561.3 μg), the minerals Se (120.0 μg), Zn (11.0 mg), Fe (15.0-18.8 mg), and Mn (5.2-12.5 mg), and polyphenols (1171.00 mg) needed to maintain an active immune response. However, all of these diets are deficient in the recommended amount of vitamin D (20 μg/d). Therefore, vulnerable populations such as elders and obese individuals could benefit from antioxidant supplementation to improve their antioxidant response. Although evidence remains scarce, there is some indication that a healthy diet, along with supplemental antioxidant intake, is beneficial to COVID-19 patients.
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Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis.
McDonnell, L, Gilkes, A, Ashworth, M, Rowland, V, Harries, TH, Armstrong, D, White, P
Gut microbes. 2021;13(1):1-18
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The gut microbiome and immune system are intricately connected and recent studies have demonstrated a link between antibiotic exposure and gut microbiome alteration in neonates. Antibiotics in childhood may be linked to a variety of diseases and although the mechanism of association for diseases has not been fully explored, the underlying cause could be linked to dysbiosis in the gut microbiome. The aim of this systematic review was to examine the association between paediatric antibiotic exposure and gut microbiome disruption. Among the existing literature, 12 studies were included and the results showed a significant reduction in both diversity and richness of the gut microbiome in children aged 0-18 following antibiotic exposure. Based on these findings, the authors conclude antibiotics appear to disrupt the normal maturation of the microbiome and alter the healthy balance of bacteria. They recommend healthcare providers consider the potential damage to the gut microbiome when prescribing antibiotics for children.
Abstract
Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying mechanisms are thought related to dysbiosis of the gut microbiome. We conducted a systematic review of the association between antibiotics and disruption of the pediatric gut microbiome. Searches used MEDLINE, EMBASE and Web of Science. Eligible studies: association between antibiotics and gut microbiome dysbiosis; children 0-18 years; molecular techniques of assessment; outcomes of microbiome richness, diversity or composition. Quality assessed by Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Meta-analysis where possible. A total of 4,668 publications identified: 12 in final analysis (5 randomized controlled trials (RCTs), 5 cohort studies, 2 cross-sectional studies). Microbiome richness was measured in 3 studies, species diversity in 6, and species composition in 10. Quality of evidence was good or fair. 5 studies found a significant reduction in diversity and 3 a significant reduction in richness. Macrolide exposure was associated with reduced richness for twice as long as penicillin. Significant reductions were seen in Bifidobacteria (5 studies) and Lactobacillus (2 studies), and significant increases in Proteobacteria such as E. coli (4 studies). A meta-analysis of RCTs of the effect of macrolide (azithromycin) exposure on the gut microbiome found a significant reduction in alpha-diversity (Shannon index: mean difference -0.86 (95% CI -1.59, -0.13). Antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be taken into account when prescribing antibiotics for children.Systematic review registration number: CRD42018094188.
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Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review.
Zheng, N, Guo, R, Wang, J, Zhou, W, Ling, Z
Frontiers in cellular and infection microbiology. 2021;11:792787
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The vaginal microbiome is an important contributor to vaginal health. Here the dominance of Lactobacilli species, alongside their antimicrobial compounds play a critical role in contributing and protecting the vaginal milieu. Conversely the disruption or absence of Lactobacilli dominance is frequently associated with vaginal disease and infections. One of the Lactobacilli species prevalent in the vaginal microbiome is Lactobacillus iners. It was long overlooked in research due to it being so difficult to culture, and it was first identified in 1999 thanks to DNA sequencing. Researchers since discovered that the relationship between L. iners and vaginal health is far more complicated and ambiguous compared to the other Lactobacilli species. This systematic review explores the current knowledge of the characteristics of L. iners and its role in vaginal health and disease. The article discusses L. iners identification, genetic make up and differences to other Lactobacilli species and how they relate to vaginal health. The article also summarizes L. iners nutrient requirements and its role in diseases like dysbiosis, bacterial vaginosis, sexually transmitted infections and biofilm formation. Furthermore the authors look at the relation between L. iners and premature birthing, fertility and menstrual cycles. A final section in discusses the antimicrobial and immune sytem activating qualities of L. iners. In light of all these findings the authors describe L . iners as a very unique Lactobacilli due to its unusual characteristics. Whether L. iners is beneficial or pathogenic for the host remains controversial, as it can adapt to high and low pH environment and is seen in health and equally dysbiotic states of infection. Hence some describe it as a transitional species that colonizes the vagina after disturbances. It may be a risk factor for infections by contributing to the onset and maintenance of dysbiotic disturbances. Further studies are needed to clarify the role of L. iners and its role on vaginal health and whether it could serve as a biomarker for vaginal inflammation. This article is a useful summary about the characteristics and role of L. iners in vaginal health in disease.
Abstract
Lactobacillus iners, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus, in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.
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Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly.
Despeghel, M, Reichel, T, Zander, J, Krüger, K, Weyh, C
Cells. 2021;10(4)
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As age advances, a gradual deterioration of immune function happens termed Immunosenescence, where different components of the immune system make a behavioural shift towards gradual decline. Immune ageing is characterized by changes in the ratio of naive memory T cells and CD4:CD8 and is associated with inflammatory cytokine production, which accelerates inflammatory ageing. This randomised controlled trial aimed to examine the effect of low-dose combined resistance and endurance training on the ageing immune system and inflammation in elderly subjects. Thirty participants (between the ages of 65 and 75) took part in a controlled low-threshold and care-oriented combined resistance and endurance training program for six weeks. This study showed an increase in CD4:CD8 ratio, decrease in low-grade inflammation and an improvement in strength capacity denoting improved immunosenescence and inflammaging among elderly participants. However, the study was conducted on a small sample for a short period. Therefore, robust long-term studies are required to elucidate further positive effects of different levels of physical activities in the elderly. Healthcare professionals can use these findings to understand how exercise influences immunosenescence and inflammation in the ageing body.
Abstract
With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.
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The COVID-19 Pandemic: a Call to Action to Identify and Address Racial and Ethnic Disparities.
Laurencin, CT, McClinton, A
Journal of racial and ethnic health disparities. 2020;7(3):398-402
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The severe acute respiratory syndrome coronavirus 2 virus was first identified in late 2019 in Wuhan, China. Various unsubstantiated reports emerged declaring that the genetic constitution of Blacks or even the presence of melanin rendered Blacks immune to the virus. This study is a call of action which reviews preliminary data on race and ethnicity in the peer-reviewed literature for citizens in America affected by COVID-19. Findings demonstrate that communities of colour (Blacks) have a higher rate of infection and death in comparison to their population percentage in the state of Connecticut. However, authors are unable to draw conclusions since race and ethnicity data is missing and the data in this paper is the earliest data available. Therefore, the authors call for action to identify and address racial and ethnic health disparities in the COVID-19 crisis.
Abstract
The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted and devastated the world. As the infection spreads, the projected mortality and economic devastation are unprecedented. In particular, racial and ethnic minorities may be at a particular disadvantage as many already assume the status of a marginalized group. Black Americans have a long-standing history of disadvantage and are in a vulnerable position to experience the impact of this crisis and the myth of Black immunity to COVID-19 is detrimental to promoting and maintaining preventative measures. We are the first to present the earliest available data in the peer-reviewed literature on the racial and ethnic distribution of COVID-19-confirmed cases and fatalities in the state of Connecticut. We also seek to explode the myth of Black immunity to the virus. Finally, we call for a National Commission on COVID-19 Racial and Ethnic Health Disparities to further explore and respond to the unique challenges that the crisis presents for Black and Brown communities.
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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.
Khadke, S, Ahmed, N, Ahmed, N, Ratts, R, Raju, S, Gallogly, M, de Lima, M, Sohail, MR
Virology journal. 2020;17(1):154
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Severe manifestations of COVID-19 infection and mortality are associated with a cytokine storm. This is an excessive inflammatory response to the infection leading to an overproduction of pro-inflammatory signalling molecules, which consequently contributes to tissue and organ damage. This literature review summarised current knowledge, as of June 2020, about virus-associated cytokine storm, virus-host interactions and immunological mechanism, to gain a better understanding of the phenomena observed in COVID-19 infections and devise better treatment strategies. The review briefly outlines the epidemiology of COVID-19, predictors of severity of disease, mode of transmission, testing, viral structure, mechanism of invasion of the host cell, replication and immune invasion and the progression of the four stages of the cytokine storm. The second part of the review discusses antiviral therapeutics of interest with a table summarising drugs, mechanism and available data. This article may be of interest to those who like to delve further into the mechanisms and immune components involved in a cytokine storm and gain an oversight of the pathways targeted by allopathic agents that have been put forward as treatment options.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.