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

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

doi:10.3390/biomedicines9091253

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.

Highlights

IntroductionMore than one year after the outbreak of Coronavirus Disease 2019 (COVID-19), it remains largely unknown why, while most infected subjects develop an asymptomatic or mild disease course, a small proportion of patients progress towards respiratory failure, requiring invasive mechanical ventilation, and some die [1,2]
We found that acute- and post-COVID-19 monocytes had a higher accessibility in the promoter region of lamin-B receptor (LBR) (Figure 4E), a gene related to protection against cellular senescence [27]
This observation is consistent with a M1-polarization of the immune response and suggests that circulating monocytes may contribute to the global inflammatory status and exacerbate the cytokine storm in severe COVID-19 cases [37,38,39]

Summary

Introduction

More than one year after the outbreak of Coronavirus Disease 2019 (COVID-19), it remains largely unknown why, while most infected subjects develop an asymptomatic or mild disease course, a small proportion of patients progress towards respiratory failure, requiring invasive mechanical ventilation, and some die [1,2]. Patients experiencing severe COVID-19 are older and present comorbidities such as hypertension, obesity or diabetes [3,4]. Higher C-reactive protein, neutrophil-to-lymphocyte ratio, lactate dehydrogenase and interleukin (IL)-6 are normally found in severe COVID-19 and predict fatal outcome [5,6,7,8].

Methods

Results

Discussion

Conclusion