In March 2025, BMC Medicine online published research entitled ‘Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6–36 months after COVID-19' (post-acute sequelae of COVID-19 also known as Long Covid)
Yang et al (2025)
Summary
10-30% of individuals experience post-acute sequelae of COVID-19 (PASC), a condition mainly characterised by respiratory symptoms like reduced diffusing capacity for carbon monoxide (DLco)
Proteomic and metabolomic profiles of 174 plasma samples were analysed from both groups
Molecular Analysis: Activation of cytoskeletal organization, glycolysis/gluconeogenesis, and suppression of gas transport and adaptive immune responses in COVID-19 convalescents
Metabolic Changes: Upregulation of metabolites involved in glutathione metabolism, amino acid metabolism (alanine, aspartate, glutamate), and ascorbate/aldarate metabolism.
Persistent Abnormalities: Pulmonary and molecular abnormalities, especially impaired DLco, persisted for 3 years in COVID-19 convalescents.
Extracts
ABSTRACT
BACKGROUND: Approximately 10–30% of individuals continue to experience symptoms classified as post-acute sequelae of coronavirus disease 2019 (COVID-19 (PASC)). PASC is a multisystem condition primarily characterized by respiratory symptoms, such as reduced diffusing capacity for carbon monoxide (DLco). Although many studies have investigated the pathogenesis of acute COVID-19, the long-term molecular changes in COVID-19 convalescents with PASC remain poorly understood.
METHODS: We prospectively recruited 70 individuals who had been diagnosed with COVID-19 from 7 January 2020 to 29 May 2020 (i.e., COVID-19 convalescents); we performed follow-up visits at 6 months, 1 year, 2 years, and 3 years after hospital discharge. Thirty-five healthy controls (CONs), recruited from a physical examination center before the COVID-19 pandemic, served as a comparison group. We explored the proteomic and metabolomic profiles of 174 plasma samples from the 70 COVID-19 convalescents and 35 CONs.
RESULTS: We performed a comprehensive molecular analysis of COVID-19 convalescents to investigate host changes up to 3 years after hospital discharge. Our multi-omics analysis revealed activation of cytoskeletal organization and glycolysis/gluconeogenesis, as well as suppression of gas transport and adaptive immune responses, in COVID-19 convalescents. Additionally, metabolites involved in glutathione metabolism; alanine, aspartate, and glutamate metabolism; and ascorbate and aldarate metabolism were significantly upregulated in COVID-19 convalescents. Pulmonary and molecular abnormalities persisted for 3 years in COVID-19 convalescents; impaired diffusing capacity for carbon monoxide (DLco) was the most prominent feature. We used this multi-omics profile to develop a model involving one protein (heterogeneous nuclear ribonucleoprotein K (HNRNPK)) and two metabolites (arachidonoyl-EA and 1-O-(2r-hydroxy-pentadecyl)-sn-glycerol)) for identification of COVID-19 convalescents with abnormal DLco.
CONCLUSIONS: These data provide insights concerning molecular sequelae among COVID-19 convalescents up to 3 years after hospital discharge, clarify mechanisms driving respiratory sequelae, and support the development of a novel model to predict reduced DLco. This longitudinal multi-omics analysis may illuminate the trajectory of altered lung function in COVID-19 convalescents.
MEA Comment
This research provides some interesting information on possible abnormalities in proteins and metabolites in the blood in people with Long Covid which may in turn be linked to abnormalities in cellular chemical pathways.
We need to be looking at whether these proteomic (the study of blood proteins) and metabolic abnormalities are also present in ME/CFS.
This is something that the ME Association is currently discussing with our research colleagues who are able to carry out this type of research. as needed.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
Charles Shepherd
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