Long-term metabolomic alterations during post-acute sequelae of COVID-19

• Published in: The Journal of immunology (1950) Vol. 210; no. 1_Supplement; pp. 236 - 236.21
• Main Authors: Wong, Andrea C, Devason, Ashwarya, Umana, Iboro C, Cox, Timothy, Dohnalová, Lenka, Meyer, Nuala J, Abramoff, Benjamin, Cherry, Sara, Thaiss, Christoph, Levy, Maayan
• Format: Journal Article
• Language: English
• Published: 01-05-2023
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.210.Supp.236.21

A large fraction of COVID-19 patients does not fully recover from the acute infection with SARS-CoV-2 but develops long-term symptoms that persist for several months. The pathobiology of such post-acute sequelae of COVID-19 (PASC, “long COVID”) remains largely enigmatic. This project is based on a discovery made by a plasma metabolomics exploration of individuals with acute SARS-CoV-2 infection, post-COVID patients that have fully recovered from the disease, and PASC patients that have persistent manifestations across a wide range of organ systems. We have found key metabolites that are altered by acute SARS-CoV-2 infection and do not recover in individuals with PASC, while returning to normal levels in post-COVID individuals who do not develop long-term symptoms. These metabolites offer a pathway-level hypothesis for a new molecular etiology underlying PASC. We have shown that viral RNA is sufficient to alter these metabolites and suggest that this can explain some of the symptoms reported by patients with long covid.
A.C.W. is supported by training grant T32-AI-055400-19. C.T. is a Pew biomedical scholar and a Kathryn W. Davis Aging Brain scholar and is supported by the NIH Director’s New Innovator Award (DP2-AG-067492), the Agilent Early Career Professor Award, and grants from the Edward Mallinckrodt Jr Foundation, the IDSA Foundation, the Thyssen Foundation, PennCHOP Microbiome Program, Penn Institute for Immunology, Penn Center for Molecular Studies in Digestive and Liver Diseases (P30-DK-050306), Penn Skin Biology and Diseases Resource-based Center (P30-AR-069589), Penn Diabetes Research Center (P30-DK-019525), Penn Institute on Aging and the Borrelli Family Pilot Grant in Lynch Syndrome. M.L. is supported by the NIH Director’s New Innovator Award (DP2-AG-067511), an American Cancer Society Scholar Award, The Pew Scholar Award, the Searle Scholar program, the Edward Mallinckrodt Jr Foundation and grants from the Abramson Cancer Center, The Penn-CHOP microbiome program, Penn Coronavirus Center Pilot, Penn Institute for Immunology, Penn Center for Molecular Studies in Digestive and Liver Diseases, Penn Center for Precision Medicine, Penn Institute on Aging, Penn Center of Excellence in Environmental Toxicology (P30-ES-013508) and the Borrelli Family Pilot Grant in Lynch Syndrome.