Autoantibodies are antibodies produced by the host's own immune system that target endogenous antigens, attacking proteins belonging to the host. The development of autoantibodies has been widely recognized in coronavirus disease 2019 (COVID-19) patients, correlated with disease severity and contributing to the symptoms of ‘long COVID-19’ that persist for months following recovery.
Corticosteroid anti-inflammatory drugs have been applied to these patients over the course of the pandemic, though the results are mixed. In a paper recently uploaded to the preprint server medRxiv*, the outcomes for such patients are collated, demonstrating a striking correlation between the development of autoantibodies and mortality.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
How was the study performed?
The group identified 51 hospitalized COVID-19 patients between the period March 10th – May 2nd 2020 that had received corticosteroids within 48 hours of admission, and serum samples were collected at this time. Enzyme-linked immunosorbent assays of the samples were run against an autoantibody array and rheumatoid factor antibody array, the latter being a specifically identified form of autoantibody against the Fc receptor of immunoglobulin G.
The serum of 23.5% of the patients tested positive on at least one of the two assays employed, while the remainder were negative in both tests. 75% of the autoantibody possessing patients died during hospitalization, while only 33% of the negative group died.
Unfortunately, this study is hampered by a small sample size and lack of controls, making it difficult to assert the influence of corticosteroids on COVID-19 outcome. The data table provided indicates that those that tested positive for the presence of autoantibodies, on average, stayed in the hospital for longer, were more commonly smokers and/or had diabetes, and were slightly older, all of which could have contributed to the development of autoantibodies or mortality in an unrelated manner.
Those that tested positive also bore heavily upregulated interleukin-6 levels in the sera, a pro-inflammatory cytokine associated with the production of autoantibodies when at high levels in COVID-19 patients. Additionally, only a small range of the many types of autoantibodies that could be produced were included in the assays, and the sera of patients that did not receive corticosteroids were not included for comparison.
Nonetheless, the authors describe the work as hypothesis-generating, suggesting that the presence of autoantibodies is the result of a state of hyperinflammation, and that modulation using corticosteroids and interleukin antagonists could be effective. Many other studies have implied that the administration of corticosteroids can be a double-edged sword with regards to treating severe cases of SARS-CoV-2 infection, in some cases appearing to have an adverse influence on mortality rate. Further comparative investigation is required before any clear conclusions can be drawn on this matter, though it could be the case that corticosteroids are contraindicated once autoantibodies are produced, as suggested by this pilot study.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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