HDL proteome remodeling associates with COVID-19 severity

J Clin Lipidol. 2021 Nov-Dec;15(6):796-804. doi: 10.1016/j.jacl.2021.10.005. Epub 2021 Oct 31.

Abstract

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.

Keywords: COVID-19; HDL; Infection; Quantitative proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apolipoproteins / blood
  • COVID-19 / blood*
  • COVID-19 / pathology*
  • Cholesterol, HDL / blood
  • Female
  • Humans
  • Lipoproteins, HDL / blood*
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Proteomics
  • Serum Amyloid A Protein / metabolism
  • Triglycerides / blood

Substances

  • Apolipoproteins
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • Serum Amyloid A Protein
  • Triglycerides
  • apolipoprotein F