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Published on: August 19, 2025
HDL proteome remodeling associates with COVID-19 severity
Douglas Ricardo Souza Junior1, Amanda Ribeiro Martins Silva1, Livia Rosa-Fernandes2
1Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, Brazil.
Insights
High-density lipoprotein (HDL) protein changes correlate with COVID-19 severity. Specific HDL proteins can predict disease severity and patient outcomes, suggesting HDL
Area of Science:
- Immunology
- Proteomics
- Infectious Diseases
Background:
- High-density lipoprotein (HDL) is known for lipid metabolism roles.
- Emerging evidence suggests HDL participates in immune responses to infections.
Purpose of the Study:
- To investigate if HDL proteome alterations correlate with Coronavirus disease 2019 (COVID-19) severity.
- To identify specific HDL proteins associated with COVID-19 disease progression.
Main Methods:
- Quantitative proteomic analysis of HDL particles from 41 COVID-19 patients.
- Patients were categorized into mild and severe symptom groups based on clinical criteria.
- Levels of 29 HDL proteins were quantified.
Main Results:
- Increased levels of SAA1, SAA2, SFTPB, APOF, and ITIH4 in severe COVID-19 patients.
- Altered HDL proteins accurately classified disease severity (4.9% error rate).
- Apolipoprotein M (APOM) in HDL showed an inverse association with mortality risk.
Conclusions:
- COVID-19 infection causes significant inflammatory remodeling of the HDL proteome.
- HDL particles may play a crucial role in the host's response to infectious diseases.
- HDL proteomic profiling shows potential for predicting COVID-19 severity and outcomes.
Background:
Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases.
Objective:
We used a quantitative proteomic approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19).
Methods:
Based on clinical criteria, subjects (n=41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects.
Results:
We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio [OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval [CI] of 0.07 to 0.72, P=0.007).
Conclusion:
Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases.
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