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.