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, α-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. In situ 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 Il6 , Il8 and Il1b genes in infected primary macrophages and DCs in vitro , and SARS-CoV-2-NP + macrophages and DCs also manifested high levels of IL-6 and IL-1β, which might directly decimate human spleens and LNs and subsequently lead to lymphocytopenia in vivo . Collectively, these results demonstrated that SARS-CoV-2 induced lymphocytopenia by promoting systemic inflammation and direct neutralization in human spleen and LNs.
【저자키워드】 COVID-19, SARS-CoV-2, macrophages, dendritic cells, lymphocytopenia, lymph nodes, spleen, 【초록키워드】 coronavirus disease, Apoptosis, Macrophage, Coronavirus disease 2019, ACE2, Cytokines, macrophages, spike, IL-6, neutralization, Transcription, peptide, C-reactive protein, Laboratory tests, Transmission, in vitro, lactate dehydrogenase, angiotensin-converting enzyme 2, dendritic cells, nucleocapsid protein, Particle, Antigen, Protein, lymphocyte, Viral, lymphocytopenia, Patient, IL-8, Post-mortem, Inflammatory cytokines, systemic inflammation, IL-10, in vivo, characteristic, mechanism, dendritic cell, Inflammatory cytokine, In situ hybridization, SARS-CoV-2 spike, Angiotensin-converting enzyme, IL-1β, Lactate, angiotensin, SARS-CoV-2 viral RNA, COVID-19 patient, Lymph node, lead, hilar lymph nodes, tissue damage, tissues, Serum level, enzyme, Elevation, fatal COVID-19, positive, organ, while, α-Hydroxybutyrate dehydrogenase, DCs, immunological, responsible, collected, demonstrated, triggered, manifested, accumulate, accumulated, electronic microscopy, LNs, 【제목키워드】 secondary, Promoting, Lymphoid Organ,