AUTHOR=Jeon Kyeongseok , Kim Yuri , Kang Shin Kwang , Park Uni , Kim Jayoun , Park Nanhee , Koh Jaemoon , Shim Man-Shik , Kim Minsoo , Rhee Youn Ju , Jeong Hyeongseok , Lee Siyoung , Park Donghyun , Lim Jinyoung , Kim Hyunsu , Ha Na-Young , Jo Hye-Yeong , Kim Sang Cheol , Lee Ju-Hee , Shon Jiwon , Kim Hoon , Jeon Yoon Kyung , Choi Youn-Soo , Kim Hye Young , Lee Won-Woo , Choi Murim , Park Hyun-Young , Park Woong-Yang , Kim Yeon-Sook , Cho Nam-Hyuk TITLE=Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1101808 DOI=10.3389/fimmu.2023.1101808 ISSN=1664-3224 ABSTRACT=Introduction

Despite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive.

Methods

Here, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients.

Results

Differential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients.

Discussion

Aberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression.