Alterations in circulating monocytes predict COVID-19 severity and include chromatin modifications still detectable six months after recovery

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room (ER) arrival, monocytes showed decreased surface molecules expression, including HLA-DR, in association to an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. These alterations were mostly normalized in post-COVID-19 patients, 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory, tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface markers and low IRF1 gene transcription in circulating monocytes at ER defined a COVID-19 patients group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patients stratification and to designing innate immunity-focused therapies. We performed ATAC sequencing using monocytes of Control patients with no Covid-19 infection, Acute Covid-19 or Post Covid-19 infection