Reply to Cimolai: Post-COVID syndrome and autoimmunity

To the Editor—The correspondence by Cimolai suggests that the activation of nonspecific polyclonal B cells could be responsible for the presence of autoantibodies after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral infections induce transient autoimmune responses with low titers of autoantibodies. However, progression of this immune state to an established autoimmune disease with production of organ- or tissue-specific autoantibodies has been described in multiple infections [1].

Some viral infections have been shown to trigger autoimmunity due to mechanisms such as epitope spreading, bystander activation, molecular mimicry, and cryptic epitopes [1]. SARS-CoV-2 shares characteristics of other viruses associated with the development of autoimmunity; these include the following:

Superantigen activity. The S protein of SARS-CoV-2 contains sequence and structure motifs similar to those of a bacterial superantigen and can bind directly to the T-cell receptor. Indeed, patients with severe COVID-19 exhibit a T-cell receptor skewing consistent with superantigen activation [2].

Molecular mimicry. Accumulating evidence demonstrates that the virus has structural similarity to host-derived components. In addition, SARS-CoV-2 has the ability to induce hyperstimulation of the immune system, leading to the synthesis of multiple autoantibodies in patients with severe coronavirus disease 2019 (COVID-19) [3]. Latent autoimmunity has been described in post–COVID-19 syndrome (PCS) and correlates with humoral response to SARS-CoV-2 [4].