{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:28:11Z","timestamp":1790742491239,"version":"4.1.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>While lymphocytopenia is a common characteristic of coronavirus disease 2019 (COVID-19), the mechanisms responsible for this lymphocyte depletion are unclear. Here, we retrospectively reviewed the clinical and immunological data from 18 fatal COVID-19 cases, results showed that these patients had severe lymphocytopenia, together with high serum levels of inflammatory cytokines (IL-6, IL-8 and IL-10), and elevation of many other mediators in routine laboratory tests, including C-reactive protein, lactate dehydrogenase, \u03b1-hydroxybutyrate dehydrogenase and natriuretic peptide type B. The spleens and hilar lymph nodes (LNs) from six additional COVID-19 patients with post-mortem examinations were also collected, histopathologic detection showed that both organs manifested severe tissue damage and lymphocyte apoptosis in these six cases. <jats:italic>In situ<\/jats:italic> hybridization assays illustrated that SARS-CoV-2 viral RNA accumulates in these tissues, and transmission electronic microscopy confirmed that coronavirus-like particles were visible in the LNs. SARS-CoV-2 Spike and Nucleocapsid protein (NP) accumulated in the spleens and LNs, and the NP antigen restricted in angiotensin-converting enzyme 2 (ACE2) positive macrophages and dendritic cells (DCs). Furthermore, SARS-CoV-2 triggered the transcription of <jats:italic>Il6<\/jats:italic>, <jats:italic>Il8<\/jats:italic> and <jats:italic>Il1b<\/jats:italic> genes in infected primary macrophages and DCs <jats:italic>in vitro<\/jats:italic>, and SARS-CoV-2-NP<jats:sup>+<\/jats:sup> macrophages and DCs also manifested high levels of IL-6 and IL-1\u03b2, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia <jats:italic>in vivo<\/jats:italic>. Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.<\/jats:p>","DOI":"10.3389\/fimmu.2021.661052","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T08:42:48Z","timestamp":1619599368000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":94,"title":["SARS-CoV-2 Induces Lymphocytopenia by Promoting Inflammation and Decimates Secondary Lymphoid 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