Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

Frontiers in Immunology

Immunology

Na-Young Ha¹  Jiwon Shon²  Hoon Kim³  Youn-Soo Choi⁴  Minsoo Kim⁴  Murim Choi⁴  Hye Young Kim⁴  Yeon-Sook Kim⁵  Hyeongseok Jeong⁵  Yuri Kim⁶  Uni Park⁷  Won-Woo Lee⁷  Kyeongseok Jeon⁷  Nam-Hyuk Cho⁸  Jaemoon Koh⁹  Yoon Kyung Jeon⁹  Hyun-Young Park^1,10  Youn Ju Rhee^1,11  Shin Kwang Kang^1,11  Man-Shik Shim^1,11  Hye-Yeong Jo^1,12  Sang Cheol Kim^1,12  Ju-Hee Lee^1,12  Donghyun Park^1,13  Siyoung Lee^1,13  Woong-Yang Park^1,14  Jayoun Kim^1,15  Nanhee Park^1,15  Hyunsu Kim^1,16  Jinyoung Lim^1,16 

[1] Chungnam National University Hospital, Biomedical Research Institute, Deajon, Republic of Korea;Department of Biohealth Regulatory Science, School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do, Republic of Korea;Department of Biohealth Regulatory Science, School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do, Republic of Korea;Biopharmaceutical Convergence Major, School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do, Republic of Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Internal Medicine, Chungnam National University School of Medicine, Deajon, Republic of Korea;Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea;Institute of Endemic Diseases, Medical Research Center, Seoul National University, Seoul, Republic of Korea;Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Republic of Korea;Wide River Institute of Immunology, Seoul National University, Hongcheon, Gangwon-do, Republic of Korea;Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea;Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea;Department of Thoracic and Cardiovascular Surgery, Chungnam National University School of Medicine, Deajon, Republic of Korea;Division of Healthcare and Artificial Intelligence, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea;Geninus Inc., Seoul, Republic of Korea;Geninus Inc., Seoul, Republic of Korea;Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea;Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea;Samsung Genome Institute, Samsung Medical Center, Seoul, Republic of Korea;

关键词: COVID-19;    SARS-CoV-2;    pneumonia;    inflammation;    IFNa;    IL-12p40;   

DOI  :  10.3389/fimmu.2023.1101808

 received in 2022-11-18, accepted in 2023-01-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

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

【 授权许可】

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Copyright © 2023 Jeon, Kim, Kang, Park, Kim, Park, Koh, Shim, Kim, Rhee, Jeong, Lee, Park, Lim, Kim, Ha, Jo, Kim, Lee, Shon, Kim, Jeon, Choi, Kim, Lee, Choi, Park, Park, Kim and Cho