The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes

yongwen chen; Zeqing Feng; Bo Diao; Rongshuai Wang; Gang Wang; Chenhui Wang; Yingjun Tan; Liang Liu; Changsong Wang; Ying Liu; Yueping Liu; Zilin Yuan; Liang Ren; Yuzhang Wu

The dysregulation of the proinflammatory cytokines like TNF-α and IL-6 has been described to promote cell necrosis and apoptosis. 20, 21 We also reported that IL-6 might involve in mediating lymphocyte reduction in severe COVID-19 patients. 14 Immunohistochemistry showed that high levels of IL-6 rather TNF-α were observed in virus infected spleen and LNs compared with sections from normal healthy controls ( Figure 5A) . Moreover, immunofluorescent double staining showed that IL-6 is primarily produced by infected macrophages (Figure 5B ). Increased transcription of several cytokines in macrophages has been described to be activated by SARS-Spike protein. 22, 23 Since SARS-CoV-2 and SARS share a highly similar Spike protein based on amino acid sequence, we reasoned that a similar phenomenon might occur with SARS-CoV-2 Spike. We thus treated human macrophage line-THP1 cells with Spike protein in vitro, and found that SARS-CoV-2 Spike protein can trigger increased Il6 expression independently of changes in Il1b and Tnfa gene transcription ( Figure 5C) . Collectively, these results suggest that SARS-CoV-2 viruses and the Spike protein, can trigger macrophages to secrete IL-6, which may accelerate lymphocytopenia.