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 presence of viral antigens would activate T cells and B cells in spleen and LNs, and thus lead to Fas and FasL mediated AICD. 17, 19 Although the level of FasL in spleens and LNs is similar in tissues from postmortem and age-match normal healthy controls, the expression of Fas is dramatically higher in virus infected tissue than healthy controls (Figure 4) . In addition to antigen persistence stimulation, some proinflammatory cytokines like IL-6, TNF-α and IFN-γ can also can mediate cellular apoptosis and necrosis. 20, 21 We focused here on IL-6 because it contributes to host defense against to several kinds of pathogen infections. 21, 29 We also reported that the serum concentration of IL-6 is negative to blood CD4 + and CD8 + T cells in COVID-19 patients. 14 Interestingly, exposure to viral Spike protein can trigger Il6 gene transcription in macrophages in vitro, and SARS-CoV-2 infected macrophage also manifested high levels of IL-6 in vivo ( Figure 5 ). 22, 23 We thereby conjecture that macrophages-derived IL-6 would trigger lymphocyte apoptosis and necrosis, while also enhancing Fas expression. Tocilizumab, a humanized anti-IL-6 receptor antibody, has been developed and approved for the treatment of rheumatoid arthritis (RA). 30, 31 Tocilizumab has also been shown to be effective against cytokine release syndrome resulting from CAR-T cell infusion against B cell acute lymphoblastic leukemia. 32 Since Tocilizumab has now been approved for use in clinical therapy for COVID-19 patients, whether tocilizumab can restore spleen and LN functions in COVID-19 patients by suppressing IL-6 signaling is an area requiring further investigation.