Hospitalized COVID-19 patients exhibit increased numbers of low density neutrophils expressing the transcription factor ARID3a

Abstract

Abstract We previously showed that individuals with systemic lupus erythematosus (SLE) and high levels of Type I inflammatory cytokines had increased numbers of low density neutrophils (LDNs) in their peripheral blood compared to healthy donors. Increased numbers of LDNs were associated with increased expression of the transcription factor ARID3a and increased interferon alpha (IFNα) production. Data from other cell types suggest that ARID3a expression occurs upstream of IFNα expression. Therefore, we sought to determine if increases in ARID3a-expressing LDNs might also occur in other severe inflammatory responses, such as infection with SARS-CoV2 where IFNα expression was known to be increased. Subjects admitted to the hospital with a confirmed diagnosis of SARS-CoV2 infection were enrolled in our IRB approved study and peripheral blood mononuclear cells from 24 patients were evaluated via flow cytometry for numbers of LDNs and ARID3a expression at the time of admission and at various time points after hospitalization. Numbers of circulating LDNs were dramatically increased in COVID patient samples at the time of hospitalization, as were percentages of those cells expressing ARID3a protein. IL-6 expression was also high in the LDNs, while IFNα expression was more variable. Over the course of two weeks, IFNα expression appeared to be associated with, or to lag just behind ARID3a expression in most patients, while IL-6 expression levels were not associated with ARID3a or IFNα expression. These data suggest that ARID3a expression is induced in LDNs in association with severe viral infection and may implicate ARID3a as a potential regulator of inflammatory pathways in infection as well as autoimmunity. Supported in part by grant NIH U19 AI06269