SARS-CoV2- infection as a trigger of humoral response against apolipoprotein A-1

Abstract

Aims: Unravelling autoimmune targets triggered by SARS-CoV-2 infection may provide crucial insights in the physiopathology of the disease and foster the development of potential therapeutic candidate targets and prognostic tools. We want to determine whether SARS-CoV-2 exposure could trigger a humoral response against apolipoprotein A-1 (anti-apoA-1 IgG) through molecular mimicry and assess its relationship to patient prognosis. Methods and Results: Anti-Spike domain 1 (SD1) IgGs, anti-apoA-1 IgGs and against mimic peptides, as well as cytokines were assessed by immunoassays on a case-control (n=101), an intensive care unit (ICU; n=126) with a 28-days follow-up, and a general population cohort (n=663) with available samples in the pre and post-pandemic period. Linear sequence homologies and antibodies cross-reactivity between apoA-1, TLR2, and Spike epitopes were identified. 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<0.0001). 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-days kinetics, reaching 82% for anti-apoA-1 seropositivity. C-statistics (CS) indicated that anti-Spike/TLR2 mimic-peptide IgGs displayed a significant prognostic accuracy for overall mortality at 28 days (CS: 0.64; p=0.02). In the general population, SARS-CoV-2 exposure increased baseline anti-apoA-1 IgG levels. Conclusions: 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.

Autoantibodies against apolipoprotein A‐1 after COVID‐19 predict symptoms persistence

“…This finding is similar to what has been reported in COVID‐19 patients admitted to the intensive care unit (ICU), where the AAA1 IgG seropositivity was found to swiftly raise from 18% upon ICU admission to 82% within 7 days of hospitalization and to closely mirror anti‐SARS‐CoV‐2 serological levels and kinetics 20 . Extending previous investigations performed so far, 20 this the fourth independent cohort validating the proof of principle that SARS‐CoV‐2 infection increases the humoral response against apoA‐1. Similarly, an increase in AAA1 IgGs has also been documented following COVID‐19 mRNA vaccine 41,42 .…”

“…AAA1 IgGs were measured as previously described, [21][22][23][24][25]34,35 in leftover sera after analyses for antibodies against SARS-CoV-2 antigens (see below). As previously published, 20 "Maxisorp plates (Nunc TM , Roskilde,) were coated with purified, human-derived delipidated and unmodified apoA-1 (20 μg/mL; 50 μL/well) for 1 h at 37°C. After being washed, all wells were blocked for 1 h with 2% bovine serum albumin (BSA) in a phosphate buffer solution (PBS) at 37°C.…”

“…In this line, it has been shown that the C‐terminus (c‐ter; amino‐acid region 1140‐1170) domain of Spike 14–17 shares sequence homology with the c‐ter of apolipoprotein A‐1 (apoA‐1), the major protein fraction component of high‐density lipoprotein (HDL). Providing that anti‐ApoA‐1 (AAA1) IgGs preferentially bind the c‐ter part of ApoA‐1, 18,19 this might explain why patients with SARS‐CoV‐2 infection trigger a humoral response against ApoA‐1, 20 an independent cardiovascular (CV) risk factor for poor prognosis 21–25 . Among others, the possible clinical relevance of COVID‐19‐induced auto‐antibodies have lately been suggested to be of significance for long‐term outcomes 26 .…”

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

“…A good example of the latter is the thrombotic events that may occur during COVID-19 in pregnancy whether systemically or focally in the placenta [39]. Within this milieu, it is not a surprise that patients with COVID-19 may develop what are believed to be autoimmune antibodies in a more plenary sense [40,41].…”

Apolipoprotein-A-I for severe COVID-19-induced hyperinflammatory states: A prospective case study

“…Alterations of the lipoprotein plasma composition were demonstrated (for instance, downregulation of apolipoproteins, clusterin, and paraoxonase) (Begue et al, 2021). In addition, SARS-CoV-2 infection also triggers a humoral response against ApoA-I that may modulate the outcome of COVID-19 (Pagano et al, 2021). Interestingly, several lines of evidence point to the role of ApoA-I in modulating inflammation and innate and adaptive immunity in various settings, suggesting a potential therapeutic use in COVID-19 (Sorokin et al, 2020).…”