A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients (12) and heathy patients (6), we identified three immunodominant linear epitopes, two of which correspond to key proteolytic sites on the spike protein (S1/S2 and S2') known to be critical for cellular entry. We show biochemical evidence that plasma positive for the epitope adjacent to the S1/S2 cleavage site inhibits furin-mediated proteolysis of spike.

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients, we identified immunodominant linear epitopes corresponding to key proteolytic sites on the spike protein.

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.