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*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer 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.

TidsskriftJournal of Clinical Lipidology
Udgave nummer6
Sider (fra-til)796-804
StatusUdgivet - 1. nov. 2021

Bibliografisk note

Funding Information:
This work was supported by awards from Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP, grants # 2013/07937-8, 2015/26722-8, 2016/00696-3, 2017/07725-1, 2018/18257-1, 2018/15549-1, 2019/25702-4, 2020/04923-0), from Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq grant # 402683/2016-1), and from Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES). D.R.S.J., A.R.M.S., and L.R.R. are recipients of FAPESP fellowships.

Publisher Copyright:
© 2021


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