Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6–36 months after COVID-19, 2025, Yang+

Longitudinal multi-omics analysis of convalescent individuals with respiratory sequelae 6–36 months after COVID-19
Yang, Huqin; Guan, Lujia; Xue, Yi; Li, Xuyan; Gao, Leyi; Zhang, Zhijin; Zhang, Haifan; Ma, Haomiao; Liu, Fengjiao; Huang, Xuan; Tong, Zhaohui; Li, Jieqiong

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.

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. 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. 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.

Link | PDF (BMC Medicine) [Open Access]

 

And also reduced DLco is not a symptom, but an investigative finding. But reduced DLCO does feature in a number of studies, though some of those will be clusters relating to severe acute disease, but not all. Eg Cluster Analysis to Identify Long COVID Phenotypes Using 129Xe Magnetic Resonance Imaging: A Multi-centre Evaluation (2024, European Respiratory Journal)

Spoiler: Some other refs

Post-COVID-19 sequelae are associated with sustained SARS-CoV-2-specific CD4+ immune responses (2025, International Immunopharmacology)

Exploring Heterogeneity of Fecal Microbiome in Long COVID Patients at 3 to 6 Months After Infection (2025, International Journal of Molecular Sciences)

Hypercoagulable Rotational Thromboelastometry During Hospital Stay Is Associated with Post-Discharge DLco Impairment in Patients with COVID-19-Related Pneumonia (2024, Viruses)

Inflammatory profiles are associated with long COVID up to 6 months after COVID-19 onset: A prospective cohort study of individuals with mild to critical COVID-19 (2024, PLOS ONE)

Deciphering Alveolo-Capillary Gas Transfer Disturbances in Patients Recovering from COVID-19 Lung Disease (2024, Journal of Personalized Medicine)

Factors associated with phenotypes of dyspnea in post-COVID-19 condition: a cross-sectional study (2024, Nature Scientific Reports)

mRNA vaccines protect from the lung microvasculature injury and the capillary blood volume loss occurring in SARS-CoV-2 paucisymptomatic infections (2024, Multidisciplinary Respiratory Medicine)

Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response (2024, Journal of Allergy and Clinical Immunology)

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge (2024, BMC Pulmonary Medicine)

Gas exchange abnormalities in Long COVID are driven by the alteration of the vascular component (2024, Multidisciplinary Respiratory Medicine)

Lung function trajectories in mild COVID-19 with two-year follow-up (2024, The Journal of Infectious Diseases)

Proteomic Evolution from Acute to Post-COVID-19 Conditions (2023, Journal of Proteome Research)

Exercise capacity following SARS-CoV-2 infection is related to changes in cardiovascular and lung function in military personnel (2023, International Journal of Cardiology)

Persistent Endothelial Lung Damage and Impaired Diffusion Capacity in Long COVID (2023, Journal of Personalized Medicine)

VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients (2023, Angiogenesis)

Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection (2023, Frontiers in Medicine)

Long-lasting dyspnoea in patients otherwise clinically and radiologically recovered from COVID pneumonia: a probe for checking persisting disorders in capillary lung volume as a cause (2022, Multidisciplinary Respiratory Medicine)