Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

This study was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 research call COV20/00181)—co-financed by the European Development Regional Fund “A way to achieve Europe” and by Consejería de Sanidad de la Comunidad de Madrid (CÍVICO study 2020/0082). R.L.G. and O.C.M. hold a research contract “Rio Hortega” (CM19/00120 and CM19/00092, respectively) from the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation. MCL holds a predoctoral fellowship (FPU19/06393) from the Spanish Ministry of Science and Innovation. ; 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 arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had 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 molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient 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 patient stratification and for designing innate immunity-focused therapies. ; Depto. de Medicina ; Fac. de Medicina ; TRUE ; Unión Europea ; Ministerio de Ciencia e Innovación (España) ; Comunidad de Madrid ; Instituto de Salud Carlos III ; pub