High frequency of anti-DSG 2 antibodies in post COVID-19 serum samples

Abstract

Background: There is growing recognition that COVID-19 does cause cardiac sequelae. The underlying mechanisms involved are still poorly understood to date. Viral infections, including COVID-19, have been hypothesized to contribute to autoimmunity, by exposing previously hidden cryptic epitopes on damaged cells to an activated immune system. Given the high incidence of cardiac involvement seen in COVID-19, our aim was to determine the frequency of anti-DSG2 antibodies in a population of post COVID-19 patients.

Methods and results: 300 convalescent serum samples were obtained from a group of post COVID-19 infected patients from October 2020 to February 2021. 154 samples were drawn 6 months post-COVID-19 infection and 146 samples were drawn 9 months post COVID infection. 17 samples were obtained from the same patient at the 6- and 9- month mark. An electrochemiluminescent-based immunoassay utilizing the extracellular domain of DSG2 for antibody capture was used. The mean signal intensity of anti-DSG2 antibodies in the post COVID-19 samples was significantly higher than that of a healthy control population (19 ± 83.2 in the post-COVID-19 sample vs. 2.1 ± 7.2 (p < 0. 0001) in the negative control healthy population). Of note, 29.3% of the post COVID-19 infection samples demonstrated a signal higher than the 90th percentile of the control population and 8.7% were higher than the median found in ARVC patients. The signal intensity between the 6-month and 9-month samples did not differ significantly.

Conclusions: We report for the first time that recovered COVID-19 patients demonstrate significantly higher and sustained levels of anti-DSG2 autoantibodies as compared to a healthy control population, comparable to that of a diagnosed ARVC group.

Keywords: ARVC; Anti DSG2 antibody; COVID 19; Cardiomyopathy.

Graphical abstract

Fig. 1

A. Comparative levels of anti-DSG2 antibody signal in male and female healthy controls (N = 65 female; N = 72 male), post-COVID-19 (N = 300; all males) and arrhythmogenic right ventricular cardiomyopathy samples (N = 5; 3 females, 2 males). The following statistical significance was observed: comparison of negative control healthy females (HC Female) to post-Covid (PC group), p ≤ 0.0001; comparison negative control HV females to ARVC group, p = 0.0003; comparison negative control healthy males (HC Males) to ARVC group, p = 0.0002. B. Comparison of levels of anti-DSG2 antibody signals in the PC (total N = 300) group by 6 (N = 154) and 9 (N = 146) months after COVID-19 infection. All p-values are based on the non-parametric rank-based Wilcoxon-Mann-Whitney 2-sided test. A. HC Female, female healthy controls; HC Male, male healthy controls; PC, post-COVID-19; ARVC, arrhythmogenic right ventricular cardiomyopathy; Control, positive control goat anti-DSG2 polyclonal antibody (R&D Systems, AF947) or NC, negative control pool of non-reactive human serum; S/NC, signal/negative control; females serum samples are denoted by dark circles and males serum samples by open circles; box and whisker limits represent 25th–75th and 10th–90th percentiles, respectively. Average assay values for 100, 200, 500 and 1000 ng/mL of control anti-DSG2 polyclonal antibody are designated with white diamonds. The assay value for the negative control is designated with a black diamond. B. 6 mo, 6 months post-COVID; 9 mo, 9 months post-COVID. Mean signal intensity levels are marked with black bars. P-values based on non-parametric rank-based Wilcoxon-Mann-Whitney 2-sided test.