Long-term consequence of SARS-CoV-2 on monocyte phenotype in COVID-19 survivors 3120

Abstract Description As the number of COVID-19 survivors continues to rise, the rates of post-acute sequalae of COVID19 (PASC) have also increased, emerging as a major public health concern. However, the role of monocytes on PASC development has not been fully explored. In this study, we aimed to determine whether monocyte dysregulation persists and contribute to driving inflammation and fibrosis after COVID-19 infection. RNA was isolated from purified monocytes from study participants who had pulmonary PASC (PPASC), had COVID-19 infection but no residual symptoms (Recovered), and had no COVID-19 infection (Healthy). We performed bulk RNA sequencing to profile monocytes to identify dysregulated genes and pathways associated with inflammation and fibrosis. In comparison to Recovered and Healthy, PPASC had an enrichment of immune activation signatures, such as neutrophil degranulation, IL8/IL-6 signaling, and macrophage response genes, while IL-10 pathway was down-regulated. Furthermore, disease prediction analysis showed that enriched genes in PPASC were linked to lung diseases such as pneumonia and lower respiratory tract disorder compared to those in Recovered. Transcriptomic analysis revealed that monocytes from PPASC individuals were continuously dysregulated with up regulation of pathways associated with immune activation, inflammation, and fibrosis. Our data demonstrate that monocyte dysregulation persists after viral resolution, impacting the pulmonary sequelae in PASC individuals. Funding Sources NIH/NIMHD (U54MD007601) Topic Categories Viral Immunology (VIR)