A distinct innate immune signature marks progression from mild to severe COVID-19

Wang, C., Xu, J., Wang, S.

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.

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic and the worst public health crisis at present. COVID-19 has been reported to be associated with diverse co-morbidities, such as pneumonia, respiratory failure, acute respiratory distress syndrome, and sepsis, that are usually associated with pathophysiological changes, including alveolar macrophage activation, lymphopenia, and thrombosis (Chen et al., 2020Fu et al., 2020Guan et al., 2020Huang et al., 2020Jose and Manuel, 2020Moore and June, 2020Wang et al., 2020Yang et al., 2020). Additionally, in addition to the lower respiratory tract and lungs, SARS-CoV-2 targets many other organs, including the liver, heart, intestine, kidneys, central nervous system, and muscles, thereby resulting in multiorgan injury, which is frequently associated with severe or even fatal outcomes (De Felice et al., 2020Varga et al., 2020Zhang C. et al., 2020). Immune dysregulation and inflammation are therefore involved in the pathogenesis of COVID-19 (Giamarellos-Bourboulis et al., 2020Moore and June, 2020). However, most of the information regarding the dysregulation of immune cells and cytokines has been obtained from studies using blood samples from patients. Therefore, it is essential to profile COVID-19-associated immune cell and pro-inflammatory cytokine responses in specific organs and tissues to improve our understanding of the pathogenesis of this disease.


Wang, C., Xu, J., Wang, S. "A distinct innate immune signature marks progression from mild to severe COVID-19" Frontiers in Microbiology (2021):