Proteomics validate circulating GDF-15 as an independent biomarker for COVID-19 severity

Simeng Bu; Léna Royston; Tsoarello Mabanga; Carolina A Berini; Cécile Tremblay; Bertrand Lebouché; Joseph Cox; Cecilia T Costiniuk; Madeleine Durand; Stephane Isnard; Jean-Pierre Routy

doi:10.3389/fimmu.2024.1377126

Proteomics validate circulating GDF-15 as an independent biomarker for COVID-19 severity

Front Immunol. 2024 Apr 15:15:1377126. doi: 10.3389/fimmu.2024.1377126. eCollection 2024.

Authors

Simeng Bu^{1

2}, Léna Royston^{1

2

3}, Tsoarello Mabanga^{1

2}, Carolina A Berini¹, Cécile Tremblay^{4

5}, Bertrand Lebouché^{1

2}, Joseph Cox^{1

2}, Cecilia T Costiniuk^{1

2}, Madeleine Durand^{4

5}, Stephane Isnard^#^{1

2}, Jean-Pierre Routy^#^{1

2

6}

Affiliations

¹ Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
² Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.
³ Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.
⁴ Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada.
⁵ Département de Microbiologie, Infectiologie et Immunologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
⁶ Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.

^# Contributed equally.

Abstract

Introduction: Growth differentiation factor 15 (GDF-15) was originally described as a stress-induced cytokine, and a biomarker of aging and cardiovascular diseases. We hypothesized that circulating GDF-15 would be associated with COVID-19 disease severity. Herein, we explored this hypothesis in a large cohort of COVID-19 patients.

Methods: Blood samples were collected from 926 COVID-19 adult patients and from 285 hospitalized controls from the Biobanque Québécoise de la COVID-19 (BQC19). COVID-19 severity was graded according to the WHO criteria. SOMAscan proteomics assay was performed on 50µL of plasma. ELISA were performed on 46 selected participants with left-over plasma to validate differences in plasma GDF-15 levels. Statistical analyses were conducted using GraphPad Prism 9.0 and SPSS. P values < 0.01 were considered significant.

Results: Proteomics showed that plasma GDF-15 levels were higher in COVID-19 patients compared to hospitalized controls. GDF-15 levels increased with COVID-19 severity. COVID-19 patients presenting with comorbidities including diabetes, cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease had higher GDF-15 levels. ELISA revealed significant elevation of GDF-15 until 30 days after hospitalization. Plasma GDF-15 elevation was correlated with older age. Moreover, GDF-15 levels correlated with pro-inflammatory cytokine interleukin-6 (IL-6) and inflammation marker C-reactive protein (CRP) as well as soluble levels of its putative receptor CD48. No association was established between anti-SARS-CoV-2 IgG levels and plasma GDF-15 levels.

Conclusions: This study confirms GDF-15 as a biomarker for COVID-19 severity. Clinical evaluation of GDF-15 levels could assist identification of persons at high-risk of progressing to severe disease, thus improving patient care.

Keywords: BQC19; COVID-19; GDF-15; SARS-CoV-2; proteomics; severity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Biomarkers* / blood
COVID-19* / blood
COVID-19* / diagnosis
Female
Growth Differentiation Factor 15* / blood
Humans
Male
Middle Aged
Proteomics* / methods
SARS-CoV-2*
Severity of Illness Index*

Substances

Growth Differentiation Factor 15
Biomarkers
GDF15 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Our work is supported by grants from the FRQS-SIDA Maladies Infectieuses network, Canadian institute of health research (Grant Numbers MOP 103230 and PJT 166049). SB is supported by a CIHR Master scholarship, SI is supported by a FRQS scholarship.