SARS-CoV-2 infection induces autoimmune antibody secretion more in lean than in obese COVID-19 patients

Abstract

Background/Objectives: Obesity decreases the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. How obesity impacts the secretion of autoimmune antibodies in COVID-19 patients, however, is not understood. The serum of adult COVID-19 patients contains autoimmune antibodies generated in response to virus-induced tissue damage and cell death leading to the release of intracellular antigens not known to be immunogenic autoantigens. The objective of this study is to evaluate the presence of autoimmune antibodies in COVID-19 patients with obesity. Subjects/Methods: Thirty serum samples from individuals who tested positive for SARS-CoV-2 infection by RT-PCR were collected from inpatient and outpatient settings. Of these, 15 were lean (BMI<25), and 15 were obese (BMI ≥30). Control serum samples were from 30 uninfected individuals, age- gender- and BMI-matched, recruited before the current pandemic. Serum IgG antibodies against two autoimmune specificities, as well as against SARS-CoV-2 Spike protein, were measured by ELISA. IgG autoimmune antibodies were specific for malondialdehyde (MDA), a marker of oxidative stress and lipid peroxidation, and for adipocyte-derived protein antigens (AD), markers of virus-induced cell death in the obese AT. Results: Our results show that SARS-CoV-2 infection induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AT antibodies with serum CRP and found a significant association between CRP and autoimmune antibodies in our cohort of lean and obese COVID-19 patients. Conclusions: Our results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population that is at higher risk of responding poorly to infection with SARS-CoV-2 compared to lean controls.

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“…However, there were trends toward a higher proportion with AT1R autoantibody positivity among severe cases versus controls (32% vs. 11%) and higher levels in those with mild COVID-19 compared with controls (median 9.5 U/mL vs. 5.9 U/mL [79]); Autoantibodies against anti-malondialdehyde (MDA) and anti-adipocytederived protein antigens (AD) are more frequent in lean than in obese COVID-19 patients compared to uninfected controls. However, serum levels of these autoantibodies are always higher in obese versus lean COVID-19 patients and associated with CRP levels [80]; Anti-neuronal or anti-glial autoantibodies (e.g., against Yo or NMDA receptor), which theoretically crossed a leaky brain-blood barrier, were universally detected in plasma and cerebrospinal fluid of 11 severely ill COVID-19 patients presenting unexplained neurological symptoms [81].…”