The SARS-CoV-2 as an instrumental trigger of autoimmunity

Abstract

Autoimmunity may be generated by a variety of factors by creating a hyper-stimulated state of the immune system. It had been established long ago that viruses are a substantial component of environmental factors that contribute to the production of autoimmune antibodies, as well as autoimmune diseases. Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) are viruses that withhold these autoimmune abilities. In a similar manner, SARS-CoV-2 may be counted to similar manifestations, as numerous records demonstrating the likelihood of COVID-19 patients to develop multiple types of autoantibodies and autoimmune diseases. In this review, we focused on the association between COVID-19 and the immune system concerning the tendency of patients to develop over 15 separate types of autoantibodies and above 10 distinct autoimmune diseases. An additional autoimmunity manifestation may be one of the common initial symptoms in COVID-19 patients, anosmia, the complete loss of the ability to sense smell, and other olfactory alterations. We summarize current knowledge on principal mechanisms that may contribute to the development of autoimmunity in the disease: the ability of SARS-CoV-2 to hyper-stimulate the immune system, induce excessive neutrophil extracellular traps formation with neutrophil-associated cytokine responses and the molecular resemblance between self-components of the host and the virus. Additionally, we will examine COVID-19 potential risk on the new-onsets of autoimmune diseases, such as antiphospholipid syndrome, Guillain-Barré syndrome, Kawasaki disease and numerous others. It is of great importance to recognize those autoimmune manifestations of COVID-19 in order to properly cope with their outcomes in the ongoing pandemic and the long-term post-pandemic period. Lastly, an effective vaccine against SARS-CoV-2 may be the best solution in dealing with the ongoing pandemic. We will discuss the new messenger RNA vaccination strategy with an emphasis on autoimmunity implications.

Keywords: Autoantibodies; Autoimmune diseases; COVID-19; Molecular mimicry; NETosis; SARS-CoV-2.

Fig. 1

A. Hyper-Stimulation of the immune system leading to autoimmune diseases and lymphoma. Three primary groups of factors, genetic, environmental and hormonal factors can lead to hyper-stimulation of the immune system when varying from their normal physiological effect. These factors may contribute to the development of autoantibodies, AIDs and even lymphoma. B. COVID-19 leading to Autoimmune Diseases. The SARS-CoV-2 may lead to AIDs though an additional mechanism, that of molecular mimicry with human self-components [[1], [2], [3], [4],12].

Fig. 2

COVID-19 and NETosis. SARS-CoV-2 viral particles invade the alveoli in the lung where they bind type 2 pneumocytes via angiotensin-converting enzyme 2 (ACE2), which is also present on the surface of many other cell types. As a result of the infection, neutrophils transmigrate into the alveoli, where NETosis is activated leading to release of decondensed chromatin (and other nuclear, possibly modified, components) and granular contents to the extracellular space. This figure was created using BioRender (https://biorender.com/). A – SARS-CoV-2 invading the alveoli. B – SARS-CoV-2 binding to the angiotensin-converting enzyme 2 of the type 2 pneumocytes. C – Neutrophil transmigrating to the alveoli. D – Neutrophil extracellular traps activation and release (NETosis). E – Enhancement of platelet aggregation induced by NETosis. F – Neutrophil cytokines and proteases degranulation. G – Modification of self-proteins in the citrullination induced by peptidylarginine deiminases.

Fig. 3

In the center appears the SARS-CoV-2. Around it, at the upper part of the figure, appear autoantibodies linked to the SARS-CoV-2-infection. At the bottom part of the figure, appear autoimmune diseases linked to the SARS-CoV-2-infection [20,[22], [23], [24], [25],[27], [28], [29], [30], [31], [32], [33], [34], [35]].