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

Utrero-Rico, Alberto; González-Cuadrado, Cecilia; Chivite-Lacaba, Marta; Cabrera-Marante, Oscar; Laguna-Goya, Rocío; Almendro-Vazquez, Patricia; Díaz-Pedroche, Carmen; Ruiz-Ruigómez, María; Lalueza, Antonio; Folgueira, María Dolores; Vázquez, Enrique; Quintas, Ana; Berges-Buxeda, Marcos J.; Martín-Rodriguez, Moisés; Dopazo, Ana; Serrano-Hernández, Antonio; Aguado, José María; Paz-Artal, Estela

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.