Imaging Mass Cytometric Analysis of Postmortem Tissues Reveals Dysregulated Immune Cell and Cytokine Responses in Multiple Organs of COVID-19 Patients

Wang, Chong; Xu, Jiqian; Wang, Shaoyuan; Pan, Shangwen; Zhang, Jiancheng; Han, Yang; Huang, Muhan; Wu, Di; Yang, Qingyu; Yang, Xiaobo; Yang, Yang; Shu, Ting; Zou, Xiaojing; Li, Ruiting; Luo, Yufeng; Yao, Runqing; Wang, Yaxin; Qiu, Yang; Wang, Yu; Zhang, Ding-Yu; Yao, Qun; Yan, Yongpan; Zhou, Xi; Shang, You

SARS-coronavirus-2–induced immune dysregulation and inflammatory responses are involved in the pathogenesis of coronavirus disease-2019 (COVID-19). However, very little is known about immune cell and cytokine alterations in specific organs of COVID-19 patients. Here, we evaluated immune cells and cytokines in postmortem tissues, i.e., lungs, intestine, liver, kidneys, and spleen of three patients with COVID-19. Imaging mass cytometry revealed monocyte, macrophage, and dendritic cell (DC) infiltration in the lung, intestine, kidney, and liver tissues. Moreover, in patients with COVID-19, natural killer T cells infiltrated the liver, lungs, and intestine, whereas B cells infiltrated the kidneys, lungs, and intestine. CD11b(+) macrophages and CD11c(+) DCs also infiltrated the lungs and intestine, a phenomenon that was accompanied by overproduction of the immunosuppressive cytokine interleukin (IL)-10. However, CD11b(+) macrophages and CD11c(+) DCs in the lungs or intestine of COVID-19 patients did not express human leukocyte antigen DR isotype. In contrast, tumor necrosis factor (TNF)-α expression was higher in the lungs, intestine, liver, and kidneys, but not in the spleen, of all COVID-19 patients (compared to levels in controls). Collectively, these findings suggested that IL-10 and TNF-α as immunosuppressive and pro-inflammatory agents, respectively,—might be prognostic and could serve as therapeutic targets for COVID-19.