Background/Purpose: A massive expanson of plasmablasts or antibody secreting cells (ASC) have been shown in severe patients with SARS-CoV-2 infection and in patients with autoimmune disease i.e. Systemic Lupus Erythematosus (SLE). The ASC responses in severe SARS-CoV-2 infections are associated with an intense extrafollicular (EF) B cell response reminiscent of flares in SLE patients. Additionally, autoantibodies against phospholipids, type-I interferons, and other targets have been reported in SARS-CoV-2 infection. These observations raise the possibility that severe SARS-CoV-2 infection results in breaks of self-tolerance to autoantigens.

Methods: Peripheral blood was prospectively collected from two groups of patients with COVID-19: 26 critically ill and 18 outpatients together with 15 healthy adults. Plasma from these samples was tested for a variety of autoimmune serologies. Additionally, we retrospectively collected data from 31 critically ill patients with COVID-19 who had autoimmune serologies ordered by their treatment team in the course of their ICU care in two academic ICUs in Atlanta, Georgia, USA.

Results: In the prospective cohort, autoantibodies were found more frequently in the plasma of critically ill subjects compared to healthy donors. Although there was no significant difference between dsDNA levels or ANA titers between groups, there were significantly higher levels of anti-carbamylated antibodies in the critically ill group. Notably, these levels were similar to levels in donors with SLE. In the retrospective cohort, 44% of patients had positive levels of ANA at ≥ 1:80 in a predominantly speckled pattern (50%). Of positive tests, 81% displayed titers of ≥1:160, with the higher titers ranging from 1:320-1:640. Anti-RNP and anti-centromere IgG titers were detected in 2 of 22 ANA+ patients. Reactivity against rheumatoid factor (10/52), phospholipids (3/52), prothrombin (2/52), and c-ANCA (2/52), with or without ANA reactivity, suggests broad autoimmune targeting. 59% of ANA+ patients displayed at least one other positive auto-reactive antibody test. Longitudinal data in seven patients showed that two subjects had increased ANA titers, one remained at 1:360, and one became negative.

Conclusion: Our findings invite two interpretations. Either patients with undocumented and pre-existing autoimmunity comprise the majority of the critical illness within our cohort or, more likely, the immunological environment of serious COVID-19 infection is sufficient to drive de novo autoreactivity against a variety of self-antigens. Longitudinal study of recovered patients will be critical in understanding the persistence of this autoreactive state, its role in the increasingly documented cases of ‘lingering’ COVID-19, and its propensity for conversion into self-sustaining autoimmunity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinically-identifiable-autoreactivity-is-common-in-severe-sars-cov-2-infection/