Abstract
Background: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights into the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We aimed at determining (a) the association between anti-SARS-CoV-2 and anti-apoA-1 humoral response and (b) the degree of linear homology between SARS-CoV-2, apoA-1 and Toll-like receptor 2 (TLR2) epitopes.
Design: Bioinformatics modelling coupled with mimic peptides engineering and competition experiments were used to assess epitopes sequence homologies. Anti-SARS-CoV-2 and anti-apoA-1 IgG as well as cytokines were assessed by immunoassays on a case-control (n = 101), an intensive care unit (ICU; n = 126) and a general population cohort (n = 663) with available samples in the pre and post-pandemic period.
Results: Using bioinformatics modelling, linear sequence homologies between apoA-1, TLR2 and Spike epitopes were identified but without experimental evidence of cross-reactivity. Overall, anti-apoA-1 IgG levels were higher in COVID-19 patients or anti-SARS-CoV-2 seropositive individuals than in healthy donors or anti-SARS-CoV-2 seronegative individuals (P < .0001). Significant and similar associations were noted between anti-apoA-1, anti-SARS-CoV-2 IgG, cytokines and lipid profile. In ICU patients, anti-SARS-CoV-2 and anti-apoA-1 seroconversion rates displayed similar 7-day kinetics, reaching 82% for anti-apoA-1 seropositivity. In the general population, SARS-CoV-2-exposed individuals displayed higher anti-apoA-1 IgG seropositivity rates than nonexposed ones (34% vs 16.8%; P = .004).
Conclusion: COVID-19 induces a marked humoral response against the major protein of high-density lipoproteins. As a correlate of poorer prognosis in other clinical settings, such autoimmunity signatures may relate to long-term COVID-19 prognosis assessment and warrant further scrutiny in the current COVID-19 pandemic.
Keywords: COVID-19; anti-apolipoprotein A-1 autoantibodies; molecular mimicry; spike protein; toll-like receptor 2.
【저자키워드】 COVID-19, Spike protein, molecular mimicry, anti-apolipoprotein A-1 autoantibodies, toll-like receptor 2., 【초록키워드】 SARS-CoV-2, IgG, Autoimmunity, intensive care, Prognosis, spike, Lipoproteins, SARS-COV-2 infection, COVID-19 pandemic, bioinformatics, peptide, cytokine, anti-SARS-CoV-2, Toll-like receptor, cross-reactivity, Protein, immunoassay, Epitopes, Cohort, anti-SARS-CoV-2 IgG, therapeutic, Case-control, target, ICU Patients, Autoimmune, receptor, General population, experiment, molecular, prognostic, epitope, seronegative, association, COVID-19 prognosis, COVID-19 patient, humoral, individual, sequence, clinical settings, sequence homology, homology, seroconversion rate, TLR2, scrutiny, experimental evidence, high-density, healthy donor, the disease, linear, were used, induce, triggered, Significant, IgG level, seropositive individual, were assessed, 【제목키워드】 SARS-COV-2 infection, humoral,