An NMR-Based Model to Investigate the Metabolic Phenoreversion of COVID-19 Patients throughout a Longitudinal Study

Rubén Gil-Redondo, Ricardo Conde, Maider Bizkarguenaga, Chiara Bruzzone, Ana Laín, Beatriz González-Valle, Milagros Iriberri, Carlos Ramos-Acosta, Eduardo Anguita, Juan Ignacio Arriaga Lariz, Pedro Pablo España Yandiola, Miguel Ángel Moran, Mario Ernesto Jiménez-Mercado, Leire Egia-Mendikute, María Luisa Seco, Hartmut Schäfer, Claire Cannet, Manfred Spraul, Asís Palazón, Nieves EmbadeShelly C. Lu, Julien Wist, Jeremy K. Nicholson, José M. Mato, Oscar Millet

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


After SARS-CoV-2 infection, the molecular phenoreversion of the immunological response and its associated metabolic dysregulation are required for a full recovery of the patient. This process is patient-dependent due to the manifold possibilities induced by virus severity, its phylogenic evolution and the vaccination status of the population. We have here investigated the natural history of COVID-19 disease at the molecular level, characterizing the metabolic and immunological phenoreversion over time in large cohorts of hospitalized severe patients (n = 886) and non-hospitalized recovered patients that self-reported having passed the disease (n = 513). Non-hospitalized recovered patients do not show any metabolic fingerprint associated with the disease or immune alterations. Acute patients are characterized by the metabolic and lipidomic dysregulation that accompanies the exacerbated immunological response, resulting in a slow recovery time with a maximum probability of around 62 days. As a manifestation of the heterogeneity in the metabolic phenoreversion, age and severity become factors that modulate their normalization time which, in turn, correlates with changes in the atherogenesis-associated chemokine MCP-1. Our results are consistent with a model where the slow metabolic normalization in acute patients results in enhanced atherosclerotic risk, in line with the recent observation of an elevated number of cardiovascular episodes found in post-COVID-19 cohorts.
Original languageEnglish
Article number1206
Issue number12
Publication statusPublished - Dec 2022


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