Beneficial Immune Regulation by Biological Response Modifier Glucans in COVID-19 and Their Envisaged Potentials in the Management of Sepsis.

Sepsis is a life-threatening condition caused by an abnormal immune response induced by infection with no approved or specific therapeutic options. We present our perspectives for the therapeutic management of sepsis through a four-way approach: (1) infection control through immune enhancement; (2) immune suppression during the initial hyper-inflammatory phase; (3) balanced immune-modulation to counter the later immune-paralysis phase; and (4) advantageous effects on metabolic and coagulation parameters throughout. COVID-19 is a virus-triggered, accelerated sepsis-like reaction that is associated with the rapid progress of an inflammatory cascade involving a cytokine storm and multiorgan failure. Here, we discuss the potential of the biological response modifiers, ß-glucans (BRMGs), in the management of sepsis based on their beneficial effects on inflammatory-immune events in COVID-19 clinical studies. In COVID-19 patients, apart from metabolic regulation, BRMGs, derived from a black yeast, Aureobasidium pullulans strain AFO-202, have been reported to stimulate immune responses. BRMGs, produced by another strain (N-163) of A. pullulans, have been implicated in the beneficial regulation of inflammatory markers and immunity, namely IL-6, C-reactive protein (CRP), D-Dimer, ferritin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCR), leucocyte-to-C-reactive protein ratio (LeCR), and leukocyte-to-IL-6 ratio (LeIR). Agents such as these ß-glucans, which are safe as they have been widely consumed by humans for decades, have potential as adjuncts for the prevention and management of sepsis as they exert their beneficial effects across the spectrum of processes and factors involved in sepsis pathology, including, but not limited to, metabolism, infection, inflammation, immune modulation, immune enhancement, and gut microbiota.

Controlled modulation of all the arms of the immunity including innate immunity by biological response modifier glucans, a simple yet potential nutritional supplement strategy to fight COVID-19.

Immune modulation, being one of the potential strategies to combat COVID-19 infection, emphasis has been laid on enhancing the innate immune response in a balanced manner. Beta (ß)-glucans have been suggested as nonspecific immunostimulatory adjuvants to beneficially boost protective antiviral immunity. Through this article, we wish to emphasize that ß-glucans not only enhance the innate immunity but also possess the capability to modulate all the arms of the immunity viz., innate, adaptive, TRIM at different sites including those postulated to be the entry site of the SARS-CoV2. Other than immune modulation capabilities, the beneficial metabolic- and coagulation-related effects of ß-glucans, a simple nutritional supplementation strategy, make them be considered for larger clinical studies to validate their prophylactic vaccine adjuvant and nutritional-based therapeutic supplement activities to effectively fight the COVID-19 pandemic. PRACTICAL APPLICATIONS: A 360° wholesome protection from viral infections is possible only when all the arms of the immune system function in a balanced and effective manner which is especially important in COVID-19. Nutritional supplementation using biological response modifier beta (ß)-glucans (BRMGs) is worth considering for large-scale clinical studies based on their track record of safety and their beneficial regulation of all the arms of the immune system.

Effects of select dietary supplements on the prevention and treatment of viral respiratory tract infections: a systematic review of randomized controlled trials.

Introduction: Viral respiratory tract infections (RTIs) have been recognized as a global public health burden. Despite current theories about their effectiveness, the true benefits of dietary supplements on the prevention and treatment of viral RTIs remain elusive, due to contradictory reports. Hence, we aimed to evaluate the effectiveness of dietary supplements on the prevention and treatment of viral RTIs.Areas covered: We systematically searched databases of PubMed, Web of Science, Scopus, and Google Scholar through 4 March 2020, to identify randomized controlled trials that evaluated the effects of consuming selected dietary supplements on the prevention or treatment of viral RTIs.Expert opinion: Thirty-nine randomized controlled trials (n = 16,797 participants) were eligible and included. Namely, vitamin D supplementation appeared to improve viral RTIs across cohorts particulate in those with vitamin D deficiency. Among the evaluated dietary supplements, specific lactobacillus strains were used most commonly with selected prebiotics that showed potentially positive effects on the prevention and treatment of viral RTIs. Further, ginseng extract supplementation may effectively prevent viral RTIs as adjuvant therapy. However, longitudinal research is required to confirm these observations and address the optimal dose, duration, and safety of dietary supplements being publicly recommended.

Chitosan, alginate, hyaluronic acid, gums, and ß-glucan as potent adjuvants and vaccine delivery systems for viral threats including SARS-CoV-2: A review.

Pathogen transmission is a widespread threat to global human health. Vaccines are very important during the outbreak of a pandemic. Destructive fractures caused by a sudden outbreak of COVID-19 have spurred vaccine production at an unprecedented rate. The strategy of an effective vaccine delivery system is opening up novel probabilities to make more immunization. Indeed, vaccination is the most successful way to prevent deaths from infectious diseases. In order to optimal immune response production or improvement in the effectiveness of vaccines, delivery systems or adjuvants are required. Natural polymers such as chitosan, alginate, hyaluronic acid, gums, and ß-glucan with antiviral activity have good potential as adjuvant or delivery systems for vaccine formulation development and design vaccine delivery devices. According to the antiviral performance and immunomodulation of these biopolymers, they will play significant characters in the anti-COVID-19 field. In this mini-review, the recent progress in vaccine development by using biopolymers is presented which, provides a reference for their research on anti-COVID-19 drugs and vaccines.

Could the Induction of Trained Immunity by ß-Glucan Serve as a Defense Against COVID-19?

As the SARS-CoV-2 virus wreaks havoc on the populations, health care infrastructures and economies of nations around the world, finding ways to protect health care workers and bolster immune responses in the general population while we await an effective vaccine will be the difference between life and death for many people. Recent studies show that innate immune populations may possess a form of memory, termed Trained Immunity (TRIM), where innate immune cells undergo metabolic, mitochondrial, and epigenetic reprogramming following exposure to an initial stimulus that results in a memory phenotype of enhanced immune responses when exposed to a secondary, heterologous, stimulus. Throughout the literature, it has been shown that the induction of TRIM using such inducers as the BCG vaccine and ß-glucan can provide protection through altered immune responses against a range of viral infections. Here we hypothesize a potential role for ß-glucan in decreasing worldwide morbidity and mortality due to COVID-19, and posit several ideas as to how TRIM may actually shape the observed epidemiological phenomena related to COVID-19. We also evaluate the potential effects of ß-glucan in relation to the immune dysregulation and cytokine storm observed in COVID-19. Ultimately, we hypothesize that the use of oral ß-glucan in a prophylactic setting could be an effective way to boost immune responses and abrogate symptoms in COVID-19, though clinical trials are necessary to confirm the efficacy of this treatment and to further examine differential effects of ß-glucan's from various sources.

Role of Immune Dysregulation in Increased Mortality Among a Specific Subset of COVID-19 Patients and Immune-Enhancement Strategies for Combatting Through Nutritional Supplements.

Background: The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. Discussion: A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of Aureobasidium pullulans strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. Conclusion: People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.