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Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

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Ozlem Altay, Muhammad Arif, Xiangyu Li, Hong Yang, Mehtap Aydın, Gizem Alkurt, Woonghee Kim, Dogukan Akyol, Cheng Zhang, Gizem Dinler-Doganay, Hasan Turkez, Saeed Shoaie, Jens Nielsen, Jan Borén, Oktay Olmuscelik, Levent Doganay, Mathias Uhlén, Adil Mardinoglu

Original languageEnglish
Article number2101222
JournalAdvanced Science
Volume8
Issue number17
DOIs
Accepted/In press2021
Published8 Sep 2021

Bibliographical note

Funding Information: O.A., M.A., and X.L. contributed equally to this work. This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation. The authors would like to thank the Plasma Profiling Facility team at SciLifeLab in Stockholm for generating the Olink data, Metabolon Inc. (Durham, USA) for generating the metabolomics data, and ChromaDex Inc. (Irvine, CA, USA) for providing NR. A.M. and H.Y. acknowledge support from the PoLiMeR Innovative Training Network (Marie Sk?odowska-Curie Grant Agreement No. 812616) which has received funding from the European Union's Horizon 2020 research and innovation programme. Funding Information: O.A., M.A., and X.L. contributed equally to this work. This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation. The authors would like to thank the Plasma Profiling Facility team at SciLifeLab in Stockholm for generating the Olink data, Metabolon Inc. (Durham, USA) for generating the metabolomics data, and ChromaDex Inc. (Irvine, CA, USA) for providing NR. A.M. and H.Y. acknowledge support from the PoLiMeR Innovative Training Network (Marie Skłodowska‐Curie Grant Agreement No. 812616) which has received funding from the European Union's Horizon 2020 research and innovation programme. Publisher Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

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