Extracellular acyl-CoA-binding protein as an independent biomarker of COVID-19 disease severity

Abstract

Background: Factors leading to severe COVID-19 remain partially known. New biomarkers predicting COVID-19 severity that are also causally involved in disease pathogenesis could improve patient management and contribute to the development of innovative therapies. Autophagy, a cytosolic structure degradation pathway is involved in the maintenance of cellular homeostasis, degradation of intracellular pathogens and generation of energy for immune responses. Acyl-CoA binding protein (ACBP) is a key regulator of autophagy in the context of diabetes, obesity and anorexia. The objective of our work was to assess whether circulating ACBP levels are associated with COVID-19 severity, using proteomics data from the plasma of 903 COVID-19 patients.

Methods: Somalogic proteomic analysis was used to detect 5000 proteins in plasma samples collected between March 2020 and August 2021 from hospitalized participants in the province of Quebec, Canada. Plasma samples from 903 COVID-19 patients collected during their admission during acute phase of COVID-19 and 295 hospitalized controls were assessed leading to 1198 interpretable proteomic profiles. Levels of anti-SARS-CoV-2 IgG were measured by ELISA and a cell-binding assay.

Results: The median age of the participants was 59 years, 46% were female, 65% had comorbidities. Plasma ACBP levels correlated with COVID-19 severity, in association with inflammation and anti-SARS-CoV-2 antibody levels, independently of sex or the presence of comorbidities. Samples collected during the second COVID-19 wave in Quebec had higher levels of plasma ACBP than during the first wave. Plasma ACBP levels were negatively correlated with biomarkers of T and NK cell responses interferon-γ, tumor necrosis factor-α and interleukin-21, independently of age, sex, and severity.

Conclusions: Circulating ACBP levels can be considered a biomarker of COVID-19 severity linked to inflammation. The contribution of extracellular ACBP to immunometabolic responses during viral infection should be further studied.

Keywords: Acyl-CoA-binding protein; BQC-19 biobank; COVID-19; SARS-CoV-2; autophagy; proteomics.

Figure 1

Plasma ACBP levels were elevated with severity in COVID-19 patients. (A) Comparison of plasma ACBP levels in hospitalized controls (n=295) and COVID-19 patients (n=903) (Mann Whitney’s test). (B) comparison of plasma ACBP levels according to disease severity in COVID-19 positive patients and hospitalized controls (mild n=267, moderate n=384, severe n=236, fatal n=24) (Kruskal Wallis’ test). (C) Receiver operating characteristic (ROC) curve comparing ACBP levels in mild vs severe and fatal COVID-19+ groups. (D) Comparison of plasma ACBP levels during the first wave (March 2020 – July 2020) with the second wave (August 2020 to August 2021, n=461) in the province of Quebec, Canada, (n=474) (Mann Whitney’s test). RFU, relative fluorescent units; ACBP, Acyl CoA Binding Protein.

Figure 2

Plasma ACBP levels were elevated in COVID-19 independently of comorbidities. (A) Plasma ACBP levels association with age in the COVID-19 negative and COVID-19 positive groups (Spearman’s test). (B) Comparison of plasma ACBP levels between COVID-19⁺ groups without (n=348) or with any comorbidity (n=587) (Mann Whitney’s test). (C) Comparison of plasma ACBP levels in COVID-19 negative participants and COVID-19 groups based on their comorbidity (Mann Whitney’s test). CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus.