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[Display omitted] • Antibody dependent disease enhancement (ADE) after vaccination has been reported in animal and clinical studies earlier. • Abnormal macrophages induced by the vaccines has been suggested as the key underlying mechanism. • We recommend a safer strategy of employing biological response modifier beta glucans as vaccine adjuvants for COVID-19, • The beta-glucans are capable of eliciting a beneficial immune response without triggering abnormal macrophage effector functions. A potential risk associated with vaccines for COVID-19 is antibody-dependent disease enhancement (ADE) in which vaccine induced antibody mediated immune responses may lead to enhanced SARS CoV- 2 acquisition or increased disease severity. Though ADE has not been clinically demonstrated with any of the COVID-19 vaccines so far, when neutralizing antibodies are suboptimal, the severity of COVID-19 has been reported to be greater. ADE is presumed to occur via abnormal macrophages induced by the vaccine based immune response by antibody-mediated virus uptake into Fc gamma receptor IIa (FcγRIIa) or by the formation of Fc-mediated excessive antibody effector functions. Beta-glucans which are naturally occurring polysaccharides known for unique immunomodulation by capability to interact with macrophages, eliciting a specific beneficial immune-response and enhancing all arms of the immune system, importantly without over-activation are suggested as safer nutritional supplement-based vaccine adjuvants for COVID-19. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] • Multiple-arm clinical trial of beta 1,3-1,6 glucans in COVID-19 patients. • Control arm could maintain IL-6 and D -DIMER levels only till day-15. • AFO-202 beta glucan consumption yielded IL-6 and D -DIMER control up to day-30. • N-163 +AFO-202 maintained NLR, LCR, LeCR with IL-6 and D -DIMER levels up to day-30. • CD4 + and CD8 + T cell levels were shown advantageous in N-163 +AFO-202 group. [ABSTRACT FROM AUTHOR]

We have evaluated the potential of a three-dimensional (3D) thermoreversible gelation polymer (TGP) matrix in enhancing miRNA 140 expression (a biomarker correlating with homeostasis and cartilage regeneration) during the in vitro expansion of osteoarthritis (OA)-affected human chondrocytes. OA-chondrocytes were cultured in two-dimensional (2D) monolayer followed by culture in 3D-TGP. miRNA 140 expression levels in cell culture supernatant followed by expression in the cell lysate of both 2D and 3D-TGP cultures were analyzed. The expression of miRNA 140 in cell culture supernatant from the 3D-TGP group was 0.001 to 0.002% that in 2D culture supernatant while in the cell lysate, miRNA 140 expression in the 3D-TGP was nearly 30-fold higher than that of 2D group. The 3D-TGP matrix allows enhanced expression of miRNA 140 in OA-affected human chondrocytes in vitro which after necessary validations can be applied in clinical transplantation to significantly improve the outcome. [Display omitted] [ABSTRACT FROM AUTHOR]