Mechanistic considerations linking SARS-CoV-2 infection, inflammation, and the loss of immune tolerance

The immune response to SARS-CoV-2 has been implicated in the onset of multiple, seemingly unrelated, autoimmune diseases. The immune response to SARS-CoV-2 has also been implicated in the unmasking and/or production of multiple autoantibodies, even in the absence of clinical disease. Despite such data, it remains unclear whether antibodies targeting antiviral signaling proteins and mitochondrial antigens reflect bystander activation or alternatively contribute to de novo viral immune escape mechanisms. With these comments in mind, a variety of professional antibody presenting cells and including lung resident macrophages of COVID-19 infected patients are impacted and dependent on the uptake of antibody-opsonized virus by Fc gamma receptors; yet infection is aborted via antibody-dependent effector mechanisms or pyroptosis, possibly leading to autoantibody production, and autoinflammatory manifestations, respectively.