Rao et al. Immune Enhancement to Combat COVID-19 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.

Conventional vaccines to combat COVID-19 through different approaches are at various stages of development. The complexity of COVID-19 such as the potential mutations of the virus leading to antigenic drift and the uncertainty on the duration of the immunity induced by the vaccine have hampered the efforts to control the COVID-19 pandemic. Thus, we suggest an alternative interim treatment strategy based on biological response modifier glucans such as the Aureobasidium pullulans AFO-202-derived β-glucan, which has been reported to induce trained immunity, akin to that induced by the Bacille Calmette-Guérin vaccine, by epigenetic modifications at the central level in the bone marrow. These β-glucans act as pathogen-associated molecular patterns, activating mucosal immunity by binding with specific pathogen recognition receptors such as dectin-1 and inducing both the adaptive and innate immunity by reaching distant lymphoid organs. β-Glucans have also been used as immune adjuvants for vaccines such as the influenza vaccine. Therefore, until a conventional vaccine is widely available, an orally consumable vaccine adjuvant that acts like biosimilars, termed as the wide-spectrum immune-balancing food-supplement-based enteric (β-WIFE) vaccine adjuvant approach, with well-reported safety is worth in-depth investigation and can be considered for a clinical trial.

BackgroundNon-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Lifestyle disorders such as obesity, diabetes and dyslipidaemia predispose to and are associated with the disease progression. Conventional modalities are mainly symptomatic, with no definite solution. Beta glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects. Aureobasidium pullulans strains AFO-202 and N-163 beta glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study.MethodsIn the STAM™ murine model of NASH, five groups were studied for eight weeks— (1) vehicle (RO water), (2) AFO-202 beta glucan; (3) N-163 beta glucan, (4) AFO-202+N-163 beta glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed.ResultsAFO-202 beta glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta glucan decreased fibrosis and inflammation significantly (p value<0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups.ConclusionThis preclinical study supports the potential of N-163 and AFO-202 beta glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH.Graphical abstract

Dyslipidemia is a major risk factor for the development of cardiovascular diseases and statins are the common drugs used to correct dyslipidemia. Herein, we report a case where the subject was a nondiabetic, dyslipidemia patient on medication with Rosuvastatin. After the intake of Rosuvastatin, his triglycerides decreased to a minimum of 220 mg/dL. In order to augment the action of Rosuvastatin, he was advised to take 1.5 mg of Nichi Glucan food supplement, which is a 1,3-1,6 Beta Glucan derived from the black yeast, Aureobasidium pullulans, daily for 2 months. At the end of 2 months, his triglyceride levels decreased from 523 mg/dL (at start of the study) to 175 mg/dL. His VLDL levels, which were 104.6 mg/dL at the start of the study decreased to 35 mg/dL and the HDL cholesterol levels increased from 27 to 38 mg/dL. This is a first of its kind report on the effect of the black yeast derived 1,3-1,6 Beta Glucans on dyslipidemia not associated with diabetes. Thus supplementation of Nichi Glucan, 1,3- 1,6 Beta Glucan derived from the black yeast along with the routine medications was beneficial to treat dyslipidemia and a larger trial is needed to confirm the effects.

Beta Glucan food supplements have been reported to be of benefit in diabetes and hyperlipidemia. We report a pilot study of the effects of Nichi Glucan, 1, 3-1, 6 Beta Glucan food supplement, in lowering the blood glucose and lipid levels in three patients with noninsulin-dependent diabetes mellitus (NIDDM) from India. These patients had increased blood glucose and lipid levels inspite of routine antidiabetic and lipid level lowering medications. Each of the participants took 1.5 g of Nichi Glucan per day with food for two months along with their routine medications. The relevant parameters to assess glycemic status and lipid levels were calculated at the baseline and at the end of two months. After two months of continuous consumption, in one patient, the HbA1c decreased from 9.1% to 7.8%, and the glycemic target of HbA1c <6.5% laid down by the International Diabetes Federation was reached in two patients. Lipid levels also decreased significantly. Based on our findings, Nichi Glucan food supplement can be considered along with routine medications in patients with Type II diabetes with hyperlipidemia. Further studies are needed to validate the results.

Direct endothelial injury by viruses and dysregulation of clotting mechanisms due to cytokine storm are the major precipitating factors of mortality in COVID-19; both are attributed to a fundamental dysregulation of the immune system. While immune dysregulation can be attributed to several factors, the risk of associated thrombogenic disruption varies across individuals. This variation depends on several factors, such as comorbidities, including diabetes, hypertension, and cardiovascular diseases. When considering ethnic variations, the vulnerability of Caucasians, African Americans and Hispanics needs to be addressed before arriving at strategies to handle thromboembolic complications, which have been identified in recent reports as the leading causes of mortality in COVID-19. Although evaluation of D-dimer and prothrombin during admission is considered to predict prognosis and mortality, there are no preventive or prophylactic strategies before hospital admission. Herein, we present our perspectives on the effect of regular supplementation with the biological response modifier beta glucan based on its relevance to immune modulation. This effect is of paramount importance in decreasing the development of severe COVID-19 and reducing mortality against the background of coagulopathy, especially in vulnerable populations.

Objective In this pilot clinical study, we report the beneficial effects of beta glucans derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients. Methods A total of 24 RT-PCR positive COVID-19 patients were recruited and randomly divided into three groups (Gr): Gr. 1 control (n=8) – Standard treatment; Gr. 2: Standard treatment + AFO-202 beta glucan (n=8); and Gr. 3, Standard treatment + combination of AFO-202 and N-163 beta glucans (n=8) for 30 days. Results There was no mortality or requirement of ventilation of the subjects in any of the groups. There was a decrease in D-Dimer values (751 ng/ml to 143.89 ng/ml) and IL-6 values (7.395 pg/ml to 3.16 pg/ml) in Gr. 1 in 15 days but the levels increased to abnormal levels on day 30 (D-Dimer: 202.5 ng/ml; IL-6 55.37 pg/ml); which steadily decreased up to day 30 in groups 2 (D-dimer: 560.99 ng/dl to 79.615; IL-6: 26.18 pg/ml to 3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25 pg/ml to 0.5 pg/ml). The same trend was observed with ESR. LCR and LeCR increased while NLR decreased significantly in Gr. 3. CD4+ and CD8+ T cell count showed relatively higher increase in Gr.3. There was no difference in CRP within the groups. Conclusion As these beta glucans are well known food supplements with a track record for safety, larger multi-centric clinical studies are recommended to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.

Objective: Cytokine storm and coagulopathy being the major causes of morbidity in Covid 19 patients, based on an earlier pilot study yielding control of IL 6 and D-Dimer, when AFO 202 and N 163 strains of Aureobasidium Pullulans produced beta glucans, were studied separately and in combination for 30 days. In this study, we evaluated the efficiency of the two variants combinations in comparison with the control arm, which underwent a conventional regimen of treatment alone, for a shorter duration. Methods: A total of 40 RT-PCR positive Covid-19 patients divided into two groups (Gr): Gr. 1 control (n=22). Standard treatment; Gr. 2 (n =18) Standard treatment + combination of AFO 202 and N 163 beta glucans for 15 days. Biomarkers of relevance to cytokine storm and coagulopathy were evaluated at baseline on Day 7 and Day 15. Results: The C-reactive protein (CRP), which declined from 33.95 ng/ml to 5.07 ng/ml in control and from 33.95 ng/ml to 5.64 ng/ml in the treatment arm on Day 7, increased to 14.6 ng/ml in the former while it continued to be under control in the treatment arm at 5.68 ng/ml on Day 15. The same trend was observed in Ferritin, whose values were 560.58 pg/ml at baseline to 261.44 pg/ml (day 7) and 182.40 pg/ml (day 15) in the treatment group, while it was 535.24 pg/ml at baseline, 116.66 pg/ml on day 7 and 291.95 pg/ml on day 15 in the control group. IL-6 showed a higher decrease in treatment group compared to the control group. The difference between day 7 and day 15 values were statically significant. Conclusion: A statistically significant control of IL-6, CRP and Ferritin in Covid 19 patients who orally consumed AFO 202 and N 163 strains of Aureobasidium Pullulans produced Beta glucans together in 15 days make us recommend this safe food supplement be consumed by Covid 19 patients along with conventional treatments, especially to the vulnerable population, as a prophylaxis amidst the prolonged pandemic with evolution of mutated strains of SARS COV2.