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

In December 2019, clusters of patients with pneumonia of unknown etiology were reported by the local health facilities in Wuhan, Hubei Province, China. 1, 2 In January 2020, the causative agent of mysterious pneumonia was identified as a novel coronavirus named as 2019 novel coronavirus (2019-nCoV) by the World Health Organization (WHO). This novel coronavirus was renamed as the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the consequent disease was designated as coronavirus disease 2019 . 3, 4 According to the daily report of the WHO, the epidemic of SARS-CoV-2 has so far caused 81961 laboratory confirmed cases and 3293 death in China. Meanwhile, the number of confirmed COVID-19 and fatalities around the world are 465315 and 21031, respectively, by 26 th March 2020. 5 The importance of the secondary lymphoid organs, including spleen and lymph nodes (LNs), for resistance against infection is well established. Tissue-resident macrophages positioned in the splenic marginal zone (MZ) that are among the first cell types to encounter invading pathogens. 6, 7 Similarly, the resident macrophages of the subcapsular sinus and hilar lymph nodes have been shown to play a protective role against viral infections by capturing viral particles. 8, 9 These macrophages present viral antigens to activate specific T cells, to induce activation, clonal proliferation, and subsequent killing of infected target cells through secretion of perforin, granzyme B, and interferon-γ etc. [10] [11] [12] Moreover, these activated T cells also egress from spleen and LNs into blood circulation and play immune surveillance roles. 13 Unfortunately, our previous work has shown that lymphocytopenia is prevalent in COVID-19 patients, especially in aged and critically ill cases, suggesting that the immune system from COVID-19 patients might be neutralized by infection. 14 Therefore, understanding the destinies of lymphocytes in secondary lymphoid organs is critical for understanding SARS-CoV-2 viral infection, and the identification of methods to boost lymphocytes and enhance the host immunity in vivo.