HDL proteome remodeling associates with COVID-19 severity

Douglas Ricardo Souza Junior, Amanda Ribeiro Martins Silva, Livia Rosa-Fernandes, Lorenna Rocha Reis, Gabrielly Alexandria, Santosh D. Bhosale, Fabio de Rose Ghilardi, Talia Falcão Dalçóquio, Adriadne Justi Bertolin, José Carlos Nicolau, Claudio R.F. Marinho, Carsten Wrenger, Martin R. Larsen, Rinaldo Focaccia Siciliano, Paolo Di Mascio, Giuseppe Palmisano*, Graziella Eliza Ronsein*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


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.

Original languageEnglish
JournalJournal of Clinical Lipidology
Issue number6
Pages (from-to)796-804
Publication statusPublished - 1. Nov 2021

Bibliographical note

Publisher Copyright:
© 2021


  • COVID-19
  • HDL
  • Infection
  • Quantitative proteomics


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