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Cell Rep
. 2021 Sep 20;109798.
doi: 10.1016/j.celrep.2021.109798. Online ahead of print.
Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-19
Dong-Min Kim 1 , Yuri Kim 2 , Jun-Won Seo 1 , Jooyeon Lee 3 , Uni Park 4 , Na-Young Ha 2 , Jaemoon Koh 5 , Hyoree Park 4 , Jae-Won Lee 4 , Hyo-Jin Ro 4 , Na Ra Yun 1 , Da Young Kim 1 , Sung Ho Yoon 1 , Yong Sub Na 1 , Do Sik Moon 1 , Sung-Chul Lim 6 , Choon-Mee Kim 7 , Kyeongseok Jeon 4 , Jun-Gu Kang 8 , Na-Yoon Jang 4 , Hyeongseok Jeong 3 , Jungok Kim 9 , Shinhyea Cheon 3 , Kyung Mok Sohn 3 , Jae Youg Moon 9 , Sungmin Kym 9 , Seung Ro Han 10 , Myung-Shin Lee 10 , Hyun-Je Kim 11 , Woong-Yang Park 12 , Ji-Yeob Choi 13 , Hyun-Woo Shin 13 , Hye-Young Kim 13 , Chung-Hyun Cho 13 , Yoon Kyung Jeon 5 , Yeon-Sook Kim 14 , Nam-Hyuk Cho 15
Affiliations
- PMID: 34587481
- PMCID: PMC8450316
- DOI: 10.1016/j.celrep.2021.109798
Abstract
Despite the worldwide effect of the coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased T helper (Th)2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation are associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of Fcγ receptor (FcγR) signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients.
Keywords: COVID-19; SARS-CoV-2; complement; eosinophil; immune complex; pneumonia.