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

Abstract

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.

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

“…Recently, the valuable beneficial effects of beta glucans, derived from two strains AFO-202 and N-163 of a black yeast Aureobasidium pullulans , were described. They were evaluated on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients, in a randomized pilot clinical study, where the supplementation with these beta glucans helped to maintain the major biomarkers of clinical severity and mortality of COVID-19, such as IL-6, D-Dimer, neutrophil to lymphocyte ratio (NLR) over 15 and 30 days, compared to those who underwent standard care alone [ 154 ]. Another recent pilot study, an open label, randomized clinical trial, investigated the potential benefit of calcitriol therapy given to 50 patients hospitalized with COVID-19 indicating an improvement in oxygenation, suggesting the need for a larger randomized trial [ 155 ].…”

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

“…β-Glucans can thus serve as effective immune-modulatory agents in sepsis, as they possess all four capabilities outlined above for sepsis management: mounting an anti-infection defense, immune suppression of proinflammatory cytokines, immune enhancement in the advanced immune-paralysis stage, and metabolic effects. Their potential as effective immunoadjuvants in sepsis can be observed from their effects in studies that have used them for COVID-19 ( 41 , 42 ). We will explain how COVID-19 is an accelerated sepsis-like reaction before we report the outcome of the studies of β-glucans in COVID-19, making them suitable treatment adjuvants in sepsis.…”

“…In addition, their biological response-modifying actions also vary ( 29 ). We have previously shown that A. pullulans -derived β-glucans are secreted by black yeast as an exopolysaccharide, thereby negating isolation or extraction methods ( 41 , 42 , 49 ). Two different strains of A. pullulans , AFO-202 and N-163, produce β-glucan as an exo-polysaccharide with the same chemical composition (C6H10O5) n but a different structural formula.…”

“…However, A. pullulans -derived β-glucans are water-soluble with higher purity and functionality, making oral administration possible. We have previously conducted two human clinical studies to study the effects of β-glucans in COVID-19 ( 41 , 42 ). Here, we observed a continuous and sustained decrease in erythrocyte sedimentation rate (ESR), D-Dimer, IL-6, and ferritin expression for up to 30 days.…”

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

“…Immunotherapies are at various stages of development aiming at augmented anticoronavirus immunity with a particular focus on the innate immune response to not only enhance it but also modulate it in a balanced manner to prevent hyperimmune activation (Schijns & Lavelle, 2020 ). Beta (β)‐glucans have been suggested to be potential nonspecific immunostimulatory adjuvants that can promote trained immunity (TRIM) to beneficially boost protective antiviral immunity apart from BCG vaccine (Geller & Yan, 2020 ), with clinical pilot studies have proven their efficacy and safety in bringing down the inflammatory and immune biomarkers associated with cytokine storm and coagulopathy in COVID‐19 patients (Pushkala et al, 2021 ; Raghavan et al, 2022 ).…”