Introduction
Infection is a common event that can disrupt immunological tolerance and, in some circumstances, lead to autoimmune disease [1].Viral infections have been linked to both the initiation of a range of autoimmune diseases and disease relapse in individuals with existing conditions [2]. For most autoimmune diseases, it is not clear whether infection is the sole precipitating event, an inevitable consequence of a genetic predisposition or whether infection is a necessary trigger in a genetically susceptible individual.
Early data suggest that autoimmune phenomena may exacerbate the immune pathology associated with SARS-CoV-2 infection or trigger long-term autoimmune complications secondary to bystander activation or molecular mimicry. There are reports of SARS-CoV-2 infection being associated with a number of autoimmune disorders including Guillain-Barre Syndrome (GBS) [3]and various cytopenias [4]. Anti-phospholipid antibodies have been detected in ~50% of hospitalised patients and linked to an increased incidence of cerebral infarction; however, the clinical relevance of this observation in COVID-19 remains controversial as anti-phospholipid antibody generation in acute illness is a common, non-specific finding [5-7]. Also, neutralising antibodies against type 1 anti-viral cytokines, Interferon (IFN)-ω and/or IFN-α have been found in over 10% of patients with COVID-19 pneumonia [8]. By screening a yeast expression library, Wang et al. identified autoantibodies against cytokines (including type 1 IFNs), CNS antigens and extracellular matrix proteins whose frequency correlated with disease severity [9].
Paediatric multisystem Inflammatory Syndrome (PIMS-TS) is a rare condition that occurs as a late complication of SARS-CoV-2 infection. Children suffering from this post-COVID inflammatory condition were also seropositive for anti-endothelial antibodies that may contribute to their pathology [10-12]. We and others are now searching for tissue specific autoantibodies in adults. Kreye and colleagues screened for CNS autoantibodies using murine brain sections identifying anti-Yo and NMDA-R as well as a variety of antibodies against epitopes including vessel endothelium [12]. Evidence has arisen that some of these antibodies may arise through cross-reactive recognition of self-antigens by antibodies specific for SARS-CoV-2[13].
Identifying the relationship between autoimmune antibody induction and COVID-19 is further complicated by the spectrum of presentations of this disease. In particular, the severity of disease may require hospitalisation and the more severe presentations of disease may influence the maintenance of autoantibodies during convalescence. To investigate any potential links between SARS-CoV-2 infection and autoantibodies we examined sera from acute and convalescent COVID-19 patients, some of whom had been hospitalised, for the presence of autoantibodies to a spectrum of antigens by indirect immunofluorescence. We identify a high frequency and wide range of clinically relevant autoantibodies in both acute and convalescent samples from COVID-19 patients. Their frequency and tissue specificity suggests that autoantibodies may contribute to the long-term consequences of COVID-19.