@article{377c9acffddc4f2c8a74b53e412629ec,
title = "Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19",
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.",
keywords = "combined metabolic activators, COVID-19, metabolomics, omics data, proteomics",
author = "Ozlem Altay and Muhammad Arif and Xiangyu Li and Hong Yang and Mehtap Aydın and Gizem Alkurt and Woonghee Kim and Dogukan Akyol and Cheng Zhang and Gizem Dinler-Doganay and Hasan Turkez and Saeed Shoaie and Jens Nielsen and Jan Bor{\'e}n and Oktay Olmuscelik and Levent Doganay and Mathias Uhl{\'e}n and Adil Mardinoglu",
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 Sk{\l}odowska‐Curie Grant Agreement No. 812616) which has received funding from the European Union's Horizon 2020 research and innovation programme. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = sep,
day = "8",
doi = "10.1002/advs.202101222",
language = "English",
volume = "8",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "17",
}