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

循环单核细胞的变化可预测 COVID-19 的严重程度,包括康复后六个月仍可检测到的染色质修饰

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作者:Alberto Utrero-Rico, Cecilia González-Cuadrado, Marta Chivite-Lacaba, Oscar Cabrera-Marante, Rocío Laguna-Goya, Patricia Almendro-Vazquez, Carmen Díaz-Pedroche, María Ruiz-Ruigómez, Antonio Lalueza, María Dolores Folgueira, Enrique Vázquez, Ana Quintas, Marcos J Berges-Buxeda, Moisés Martín-Rodrigue

Abstract

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.

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