Adaptive Immunity and the Risk of Autoreactivity in COVID-19

Abstract

While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body’s adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.

Systemic Sclerosis (SSc) After COVID-19: A Case Report

“…One mechanism through which SARS-CoV-2 infection is thought to lead to the development of autoimmunity is that of molecular mimicry. Molecular mimicry happens when the same lymphocyte receptor recognizes both a self-protein and a foreign antigen because of their structural similarity, which can lead to immune cross-reactivity [ 8 ]. Molecular mimicry is known to have an important role in the pathogenesis of systemic rheumatologic disorders like SLE, rheumatoid arthritis, Sjogren syndrome, and SSc [ 6 ].…”

An Interesting Case of Fatal Myasthenic Crisis Probably Induced by the COVID-19 Vaccine

“…The plausible explanations for the induction of a myasthenic crisis by the COVID-19 vaccine may be attributed to two possible mechanisms: molecular mimicry, and bystander activation. In the former, antigens produced from the mRNA vaccine are recognized by the body as being similar to host tissue antigens resulting in the formation of antibodies that are cross-reactive to both the COVID-19 virus as well as proteins present at the post-synaptic membrane such as AChRs, MuSK receptor, LDL receptor-4, or agrin [ 13 ]. In the bystander hypothesis, a previously existing self-antigen is released after activation of the immune system by the vaccine thus resulting in activation of T-cells.…”

“…This immune response leads to enhanced targeting and destruction of proteins at the NMJ, resulting in further deterioration of the condition. Given the present case, the bystander hypothesis is more applicable due to the existing diagnosis of MG; however, molecular mimicry may have also been involved in the exacerbation of the disease [ 13 , 14 ].…”

SARS-CoV-2 and human retroelements: a case for molecular mimicry?

“…Relating to SARS, the autoantibodies’ target, LINE1 ORF2p, was prominently stained post-mortem in lung macrophages (residing in blood vessels), leading the authors to suspect a build-up of autoreactive CD4+ Th cells and, thus, an autoimmune loop in SARS [ 55 ]. Importantly, there is also increasing evidence for an autoimmune pathogenesis in severe COVID-19 [ 13 – 27 , 66 , 67 ]. One explanation for autoantibody formation is by molecular mimicry, i.e.…”