Biological and Clinical Factors Contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19.
Angelo D'Alessandro,Tiffany Thomas,Imo J. Akpan,Julie A. Reisz,Francesca Cendali,Fabia Gamboni,Travis Nemkov,Kiruphagaran Thangaraju,Upendra K. Katneni,Kenichi Tanaka,Stacie Kahn,Alexander Wei,Jacob E. Valk,Krystalyn E. Hudson,David Roh,Chiara Moriconi,James C. Zimring,Eldad A. Hod,Steven L. Spitalnik,Paul W. Buehler,Richard O. Francis +20 more
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TLDR
In this paper, a large-scale study was conducted to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive or negative for COVID-19.Abstract:
The Corona Virus Disease 2019 (COVID-19) pandemic represents an ongoing worldwide challenge. The present large study sought to understand independent and overlapping metabolic features of samples from acutely ill patients (n = 831) that tested positive (n = 543) or negative (n = 288) for COVID-19. High-throughput metabolomics analyses were complemented with antigen and enzymatic activity assays on plasma from acutely ill patients collected while in the emergency department, at admission, or during hospitalization. Lipidomics analyses were also performed on COVID-19-positive or -negative subjects with the lowest and highest body mass index (n = 60/group). Significant changes in amino acid and fatty acid/acylcarnitine metabolism emerged as highly relevant markers of disease severity, progression, and prognosis as a function of biological and clinical variables in these patients. Further, machine learning models were trained by entering all metabolomics and clinical data from half of the COVID-19 patient cohort and then tested on the other half, yielding ~78% prediction accuracy. Finally, the extensive amount of information accumulated in this large, prospective, observational study provides a foundation for mechanistic follow-up studies and data sharing opportunities, which will advance our understanding of the characteristics of the plasma metabolism in COVID-19 and other acute critical illnesses.read more
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l-Arginine and COVID-19: An Update.
Ayobami Adebayo,Fahimeh Varzideh,Scott Wilson,Jessica Gambardella,Michael Eacobacci,Stanislovas S. Jankauskas,Kwame Donkor,Urna Kansakar,Valentina Trimarco,Pasquale Mone,Angela Lombardi,Gaetano Santulli +11 more
TL;DR: In this paper, an updated systematic overview of the current evidence on the functional contribution of L-Arginine in COVID-19, describing its actions on endothelial cells and the immune system and discussing its potential as a therapeutic tool, emerged from recent clinical experimentations.
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Signatures of Mitochondrial Dysfunction and Impaired Fatty Acid Metabolism in Plasma of Patients with Post-Acute Sequelae of COVID-19 (PASC)
Vamsi P. Guntur,Travis Nemkov,Esther de Boer,Michael P. Mohning,David Baraghoshi,Francesca Cendali,Iñigo San-Millán,Irina Petrache,Angelo D'Alessandro +8 more
TL;DR: PASC plasma metabolites are indicative of altered fatty acid metabolism and dysfunctional mitochondria-dependent lipid catabolism, consistent with previously reported mitochondrial dysfunction during exercise, and may pave the way for therapeutic intervention focused on restoring mitochondrial fat-burning capacity.
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Targeting Arginine in COVID-19-Induced Immunopathology and Vasculopathy
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Severe COVID-19 Is Characterised by Perturbations in Plasma Amines Correlated with Immune Response Markers, and Linked to Inflammation and Oxidative Stress
Naama Karu,Alida S.D. Kindt,Adriaan J. van Gammeren,Anton A.M. Ermens,Amy C. Harms,Lützen Portengen,Roel Vermeulen,Willem A. Dik,Anton W. Langerak,V H J van der Velden,Thomas Hankemeier +10 more
TL;DR: The overall metabolic picture of severe COVID-19 reflected enhanced metabolic demands to maintain cell proliferation and redox balance, alongside increased inflammation and oxidative stress.
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Skeletal Muscle and COVID-19: The Potential Involvement of Bioactive Sphingolipids
TL;DR: In this article , a review summarizes the consequences of SARS-CoV-2 infection on SkM and the potential involvement of sphingosine 1-phosphate signaling in the tissue responses to virus infection.
References
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Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Journal ArticleDOI
Endothelial cell infection and endotheliitis in COVID-19.
Zsuzsanna Varga,Andreas J. Flammer,Peter Steiger,Martina Haberecker,Rea Andermatt,Annelies S. Zinkernagel,Mandeep R. Mehra,Reto A. Schuepbach,Frank Ruschitzka,Holger Moch +9 more
TL;DR: The vascular endothelium is an active paracrine, endocrine, and Endothelial cell infection and endotheliitis in COVID-19 and recruitment of immune cells can result in widespread endothelial dysfunction associated with apoptosis.
Journal ArticleDOI
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.
David E. Gordon,Gwendolyn M. Jang,Mehdi Bouhaddou,Jiewei Xu,Kirsten Obernier,Kris M. White,Matthew J. O’Meara,Veronica V. Rezelj,Jeffrey Z. Guo,Danielle L. Swaney,Tia A. Tummino,Ruth Hüttenhain,Robyn M. Kaake,Alicia L. Richards,Beril Tutuncuoglu,Helene Foussard,Jyoti Batra,Kelsey M. Haas,Maya Modak,Minkyu Kim,Paige Haas,Benjamin J. Polacco,Hannes Braberg,Jacqueline M. Fabius,Manon Eckhardt,Margaret Soucheray,Melanie J. Bennett,Merve Cakir,Michael McGregor,Qiongyu Li,Bjoern Meyer,Ferdinand Roesch,Thomas Vallet,Alice Mac Kain,Lisa Miorin,Elena Moreno,Zun Zar Chi Naing,Yuan Zhou,Shiming Peng,Ying Shi,Ziyang Zhang,Wenqi Shen,Ilsa T Kirby,James E. Melnyk,John S. Chorba,Kevin Lou,Shizhong Dai,Inigo Barrio-Hernandez,Danish Memon,Claudia Hernandez-Armenta,Jiankun Lyu,Christopher J.P. Mathy,Tina Perica,Kala Bharath Pilla,Sai J. Ganesan,Daniel J. Saltzberg,Rakesh Ramachandran,Xi Liu,Sara Brin Rosenthal,Lorenzo Calviello,Srivats Venkataramanan,Jose Liboy-Lugo,Yizhu Lin,Xi Ping Huang,Yongfeng Liu,Stephanie A. Wankowicz,Markus Bohn,Maliheh Safari,Fatima S. Ugur,Cassandra Koh,Nastaran Sadat Savar,Quang Dinh Tran,Djoshkun Shengjuler,Sabrina J. Fletcher,Michael C. O’Neal,Yiming Cai,Jason C.J. Chang,David J. Broadhurst,Saker Klippsten,Phillip P. Sharp,Nicole A. Wenzell,Duygu Kuzuoğlu-Öztürk,Hao-Yuan Wang,Raphael Trenker,Janet M. Young,Devin A. Cavero,Devin A. Cavero,Joseph Hiatt,Joseph Hiatt,Theodore L. Roth,Ujjwal Rathore,Ujjwal Rathore,Advait Subramanian,Julia Noack,Mathieu Hubert,Robert M. Stroud,Alan D. Frankel,Oren S. Rosenberg,Kliment A. Verba,David A. Agard,Melanie Ott,Michael Emerman,Natalia Jura,Mark von Zastrow,Eric Verdin,Eric Verdin,Alan Ashworth,Olivier Schwartz,Christophe d'Enfert,Shaeri Mukherjee,Matthew P. Jacobson,Harmit S. Malik,Danica Galonić Fujimori,Trey Ideker,Charles S. Craik,Stephen N. Floor,James S. Fraser,John D. Gross,Andrej Sali,Bryan L. Roth,Davide Ruggero,Jack Taunton,Tanja Kortemme,Pedro Beltrao,Marco Vignuzzi,Adolfo García-Sastre,Kevan M. Shokat,Brian K. Shoichet,Nevan J. Krogan +128 more
TL;DR: A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
Journal ArticleDOI
Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.
Bette T. Korber,Will Fischer,Sandrasegaram Gnanakaran,Hyejin Yoon,James Theiler,Werner Abfalterer,Nick Hengartner,Elena E. Giorgi,Tanmoy Bhattacharya,Brian T. Foley,Kathryn M. Hastie,Matthew Parker,David G Partridge,Cariad Evans,Timothy M. Freeman,Thushan I de Silva,Adrienne Angyal,Rebecca Brown,Laura Carrilero,Luke R. Green,Luke R. Green,Luke R. Green,Danielle C. Groves,Katie Johnson,Alexander J Keeley,Benjamin B Lindsey,Paul J. Parsons,Mohammad Raza,Sarah Rowland-Jones,Nikki Smith,Rachel Tucker,Dennis Wang,Matthew Wyles,Charlene McDanal,Lautaro G. Perez,Haili Tang,Alex Moon-Walker,Alex Moon-Walker,Alex Moon-Walker,Sean P. J. Whelan,Celia C. LaBranche,Erica Ollmann Saphire,David C. Montefiori +42 more
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.
Journal ArticleDOI
Endothelial Dysfunction A Marker of Atherosclerotic Risk
TL;DR: Given its reversibility and granted the availability of a diagnostic tool to identify patients at risk and to control the efficacy of therapy in clinical practice, endothelial dysfunction may be an attractive primary target in the effort to optimize individualized therapeutic strategies to reduce cardiovascular morbidity and mortality.