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
Kadalraja Raghavan, Vidyasagar Devaprasad Dedeepiya, Vaddi Suryaprakash, Kosagi-Sharaf Rao, Nobunao Ikewaki, Tohru Sonoda, Gary A Levy, Masaru Iwasaki, Rajappa Senthilkumar, Senthilkumar Preethy, Samuel Jk Abraham
Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2021.112243
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
Ethics approval and consent to participate The study was registered in India's clinical trial registry CTRI, Ref no: CTRI/2021/04/032766 (http://ctri.nic.in/Clinicaltrials/pmaindet2.ph p?trialid=54786). The study was approved by the Institutional Ethics Committee (IEC) of Shanmuga Medical Research Foundation Trust-Institutional Ethics Committee, India on 29th March, 2021.
Funding No external funding was received for the study.
CRediT authorship contribution statement
Conflict of interest statement Author Samuel Abraham is a shareholder in GN Corporation, Japan which in turn is a shareholder in the manufacturing company of the Beta Glucans described in the study. Author contribution statement K.R, V.D and S.A. contributed to conception and design of the study. N.I helped with technical inputs. R.S helped in literature search. S.A, G.L and S.P. drafted the manuscript. V.S, K.S.R, T.S and M.I performed critical revision of the manuscript. All the authors read, and approved the submitted version.
References
Aikewaki, Iwasaki, Abraham, Biological response modifier glucan through balancing of blood glucose may have a prophylactic potential in COVID-19 patients, J. Diabetes Metab. Disord
Aikewaki, Iwasaki, Kurosawa, Rao, Lakey-Beitia et al., beta glucans: wide-spectrum immune-balancing food-supplementbased enteric (β-WIFE) vaccine adjuvant approach to COVID-19, Hum. Vaccin. Immunother
Bikewaki, Raghavan, Dedeepiya, Suryaprakash, Iwasaki et al., Beneficial immune-regulatory effects of novel strains of Aureobasidium pullulans AFO-202 and N-163 produced beta glucans in Sprague Dawley rats,
doi:10.21203/rs.3.rs-771315/v1
Bikewaki, Rao, Archibold, Iwasaki, Senthilkumar et al., Coagulopathy associated with COVID-19 -perspectives & Preventive strategies using a biological response modifier Glucan!Abstract, Thromb. J
Bioithas, The intestinal microbiota as a therapeutic target in hospitalized patients with COVID-19 infection
Ciecierska, Drywień, Hamulka, Sadkowski, Nutraceutical functions of beta-glucans in human nutrition, Rocz. Panstw. Zakl. Hig
Coomes, Haghbayan, Interleukin-6 in Covid-19: a systematic review and meta-analysis, Rev. Med. Virol
Dhar, Mohanty, Gut microbiota and Covid-19-possible link and implications, Virus Res
Dikewaki, Sonoda, Kurosawa, Iwasaki, Dedeepiya et al., Immune and metabolic beneficial effects of Beta 1,3-1,6 glucans produced by two novel strains of Aureobasidium pullulans in healthy middle-aged Japanese men: an exploratory study,
doi:10.1101/2021.08.05.21261640
Eikewaki, Dedeepiya, Iwasaki, Abraham, Commentary: beyond "TRIM" benefits of β-glucan by blood glucose and lipid balancing potentials in its defense against COVID-19, Front. Immunol
Ghahramani, Tabrizi, Lankarani, Kashani, Rezaei et al., Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: a systematic review and meta-analysis, Eur. J. Med. Res
Ikewaki, Fujii, Onaka, Ikewaki, Inoko, Immunological actions of Sophy beta-glucan (beta-1,3-1,6 glucan), currently available commercially as a health food supplement, Microbiol. Immunol
Leaf, Ginde, Vitamin D3 to Treat COVID-19: different disease, same answer, JAMA
Mejía, Medina, Cornejo, Morello, Vásquez et al., Oxygen saturation as a predictor of mortality in hospitalized adult patients with COVID-19 in a public hospital in Lima, Peru, PLoS One
Musoke, Lo, Albano, Peterson, Bhargav et al., Anticoagulation and bleeding risk in patients with COVID-19, Thromb. Res
Pu, Zhang, Liu, Ye, Li, Unexplained elevation of erythrocyte sedimentation rate in a patient recovering from COVID-19: A case report, World J. Clin. Cases
Rao, Suryaprakash, Senthilkumar, Preethy, Katoh et al., Role of immune dysregulation in increased mortality among a specific subset of COVID-19 patients and immune-enhancement strategies for combatting through nutritional supplements, Front. Immunol
Sabaka, Koščálová, Straka, Hodosy, Lipták et al., Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a long-term care facility during Covid-19 outbreak, BMC Infect. Dis
Sabico, Enani, Sheshah, Aljohani, Aldisi et al., Effects of a 2-week 5000 IU versus 1000 IU vitamin D3 supplementation on recovery of symptoms in patients with mild to moderate COVID-19: a randomized clinical trial, Nutrients
Silberstein, Vitamin D: a simpler alternative to tocilizumab for trial in COVID-19?, Med. Hypotheses
Soni, Gopalakrishnan, Vaishya, Prabu, D-dimer level is a useful predictor for mortality in patients with COVID-19: analysis of 483 cases, Diabetes Metab. Syndr
Stroehlein, Wallqvist, Iannizzi, Mikolajewska, Metzendorf et al., Vitamin D supplementation for the treatment of COVID-19: a living systematic review, Cochrane Database Syst. Rev
Thomas, Patel, Bittel, Wolski, Wang et al., Effect of high-dose zinc and ascorbic acid supplementation vs usual care on symptom length and reduction among ambulatory patients With SARS-CoV-2 infection: the COVID A to Z randomized clinical trial, JAMA Netw. Open
Varchetta, Mele, Oliviero, Mantovani, Ludovisi et al., Unique immunological profile in patients with COVID-19, Cell. Mol. Immunol
Weill, Plissonneau, Legrand, Rioux, Thibault, May omega-3 fatty acid dietary supplementation help reduce severe complications in Covid-19 patients?, Biochimie
Wen, Jiang, Gao, Zhou, Xiao et al., Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study, BMC Infect. Dis
Winthrop, Mariette, To immunosuppress: whom, when and how? That is the question with COVID-19, Ann. Rheum. Dis
Yu, Qin, Chen, Wang, Tian, D-dimer level is associated with the severity of COVID-19, Thromb. Res
Zhang, Kang, Gong, Xu, Wang et al., The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes,
doi:10.1101/2020.01.30.927806
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