Beneficial effects of novel aureobasidium pullulans strains produced beta-1,3-1,6 glucans on interleukin-6 and D-dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study.

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 (7.395-3.16 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: 26.18-3.41 pg/ml) and 3 (D-dimer: 1614 ng/dl to 164.25 ng/dl; IL-6: 6.25-0.5 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.

Beneficial immune-regulatory effects of novel strains of Aureobasidium pullulans AFO-202 and N-163 produced beta glucans in Sprague Dawley rats (preprint)

Background: Immune system dysregulation plays a significant role in the pathogenesis of COVID-19. A balanced immune response is essential to mounting anti-viral defences, and biomarkers such as the white blood cell (WBC) count, the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-C-reactive-protein (LCR) ratio have been reported as potential predictors of immune status. The beneficial immunomodulation effects of a biological response modifier glucan (BRMG) produced by two strains of Aureobasidium pullulans , AFO-202 and N-163, were reported in earlier in vitro studies. In this study, we compared their efficacy on immune-inflammatory parameters in Sprague Dawley (SD) rats. Methods: : This study was performed on four groups of healthy SD rats, with six subjects in each group: Group 1, which was euthanised on Day 0 to obtain baseline values; Group 2, which served as the control (drinking water); Group 3, which received AFO-202 beta glucan at a dose of 200 mg/kg/day; and Group 4, which received N-163 beta glucan at a dose of 300 mg/kg/day. Test solutions were administered to the animals in Groups 2–4 by gavage once daily for 28 consecutive days. Biochemical analyses were conducted on haematological, immunological and inflammatory biomarkers on Days 15 and 29. Results: : The NLR decreased, whereas the LCR and leukocyte-to-C-reactive protein ratio (LeCR) increased in Group 3 (AFO-202) at 15 days, but the values were within the normal physiological range only. At 29 days, this difference among the groups was not observed. There were no significant differences between the groups in the other parameters, such as red blood cell (RBC) count, WBC count, CRP, IgA, IL-6, IFN-γ and sFAS. Conclusion: AFO-202 beta glucan helps marginally decrease NLR and increase LCR and LeCR in healthy SD rats within 15 days. This might be beneficial to tackling infections such as COVID-19 that involve immune system dysregulation. These results warrant further investigations in larger numbers of healthy and diseased models to develop appropriate strategies for balancing immune system dysregulation using these beta glucan food supplements with proven safety.

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.