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

We then sought to investigate the route and identities of the cells that could potentially contribute to SARS-CoV-2 transports into spleens and LNs. From our in situ immunohistochemistry, we showed that viral NP antigen was restricted to the macrophages of the infected tissues, while, human T cells and B cells were negative for viral NP antigen, suggesting SARS-CoV-2 cannot directly infect T and B cells ( Figure 2B ). Most importantly, viral NP + CD68 + macrophages were observed in capillaries of spleens and LNs, indicating that SARS-CoV-2 migrates into spleens and LNs through macrophages. An interesting finding is that overwhelming numbers of NP + cells are observed in red pulp of spleens and within marginal sinus of lymph nodes (Figure 2A) . Previous work have showed that tissue-resident CD169 + macrophages are positioned in the splenic MZ and reside in the subcapsular sinus of LNs. 7, 16 The strategic anatomical positioning of CD169 + macrophages in the spleen and LNs suggest these cells are the first to interact with invading pathogen. Here, we also found that most CD169 + macrophages are positive for viral NP antigens ( Figure 2B) . We therefore reasoned that the CD169 + macrophages play a central role in mediating SARS-CoV-2 translocation in spleens and LNs, and thus contribute to viral growth and spread.