Long-term dysregulation of plasma peptidome in mild and multiple COVID-19 recovered patients revealed by a novel efficient peptidomics workflow
Related Experiment Video
Updated: Jun 5, 2025
TMT Sample Preparation for Proteomics Facility Submission and Subsequent Data Analysis
Published on: June 8, 2020
Zhijing Song1,2,3, Chaoran Liu1, Yaozhou Liu1,4
1Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Abstract:
After recovering from COVID-19, many patients experience "long COVID" symptoms. Existing research has predominantly focused on moderate to severe cases, with limited studies examining mild cases and recurrent infections. The circulating low-molecular-weight (LMW) peptidome, involving lipid metabolism, coagulation, and immune pathways, is crucial for understanding COVID-19's long-term effects. We developed a peptidomics workflow utilizing solid-phase extraction with highly wrinkled GO-Fe3O4 composite materials (HWGO-F) and nanoLC-MS/MS detection. By altering the pH, HWGO-F enhances plasma peptide adsorption and purification. Compared to traditional methods, our workflow offers improved detection depth and reproducibility for over 70% of peptide signals with CV < 20%. We investigated plasma peptide profiles in mild COVID-19 patients post-recovery from single or second infections. The findings indicate persistent abnormalities in initial COVID-19 infections' plasma peptide profiles, gradually diminishing over time. Secondary infections prolong recovery. Disrupted functions include lipid metabolism, coagulation and complement cascades, and infection-related pathways. Lipid metabolism may normalize within 3 months, while coagulation and immune abnormalities can last 3-6 months. After secondary infections, lipid metabolism irregularities may last at least 1 month, with extended coagulation and immune imbalances. These results provide a theoretical foundation for understanding the widespread occurrence of long COVID and guide recovery care for mild cases.
Insights
Long COVID symptoms persist after mild COVID-19, especially with reinfection. Our new method reveals lasting impacts on lipid metabolism, coagulation, and immune pathways, guiding recovery for mild cases.
Area of Science:
- Biochemistry
- Immunology
- Proteomics
Background:
- Long COVID affects many post-COVID-19 recovery, with limited research on mild cases and reinfections.
- The low-molecular-weight (LMW) peptidome, involving lipid metabolism, coagulation, and immune pathways, is key to understanding long COVID.
- Existing research often overlooks mild COVID-19 cases and the impact of recurrent infections.
Purpose of the Study:
- To develop an advanced peptidomics workflow for analyzing plasma peptide profiles in mild COVID-19 patients.
- To investigate the long-term effects of single and secondary COVID-19 infections on the LMW peptidome.
- To identify specific metabolic and immune pathways affected by long COVID and recurrent infections.
Main Methods:
- Developed a novel peptidomics workflow using wrinkled graphene oxide-iron oxide (GO-Fe3O4) composite materials (HWGO-F) for enhanced plasma peptide adsorption and purification.
- Utilized nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) for sensitive peptide detection.
- Optimized peptide adsorption by adjusting the pH of the HWGO-F material.
Main Results:
- The HWGO-F workflow demonstrated improved detection depth and reproducibility (CV < 20% for >70% of signals) compared to traditional methods.
- Persistent abnormalities in plasma peptide profiles were observed in mild COVID-19 patients, gradually resolving over time.
- Secondary infections were found to prolong recovery, with extended disruptions in lipid metabolism, coagulation, and immune pathways.
Conclusions:
- Mild COVID-19 can lead to persistent peptidomic alterations, particularly affecting lipid metabolism, coagulation, and immune functions.
- Lipid metabolism abnormalities may resolve within 3 months, while coagulation and immune issues can persist for 3-6 months after initial infection.
- Secondary infections exacerbate these imbalances, highlighting the need for tailored recovery strategies for mild COVID-19 cases.
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