Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-19
Dong‐Min Kim, Yuri Kim, Yuri Kim, Jun-Won Seo, Joo-Yeon Lee, Uni Park, Na‐Young Ha, Jaemoon Koh, Hyoree Park, Jaewon Lee, Hyo‐Jin Ro, Na Ra Yun, Da Young Kim, Sung Ho Yoon, Yong Sub Na, Do Sik Moon, Sung‐Chul Lim, Choon‐Mee Kim, Kyeongseok Jeon, Jun‐Gu Kang, Nayoon Jang, Hyeongseok Jeong, Jungok Kim, Shinhyea Cheon, Kyung Mok Sohn, Jae Youg Moon, Sungmin Kym, Seung Ro Han, Myung‐Shin Lee, Hyun Je Kim, Woong‐Yang Park, Ji‐Yeob Choi, Hyun‐Woo Shin, Hye‐Young Kim, Chung‐Hyun Cho, Yoon Kyung Jeon, Yeon-Sook Kim, Yeon-Sook Kim, Nam‐Hyuk Cho
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.