The Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes

Abstract

While lymphocytopenia is a common characteristic of patients infected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the mechanisms responsible for this depletion are unclear. Through careful inspection of the spleens and lymph nodes (LNs) from six cases with postmortem examinations, we observed that SARS-CoV-2 could directly infect secondary lymphoid organs to induce cell death. Immunohistochemistry demonstrated ACE2 (angiotensin-converting enzyme 2), the potential receptor of SARS-CoV-2, expresses on tissue-resident CD169+ macrophages in spleens and LNs. Immunofluorescent staining confirmed that viral nucleocaspid protein (NP) can be found in ACE2+ cells, CD169+ macrophages, but not in CD3+ T cells or B220+ B cells in spleens and LNs. SARS-CoV-2 infection induces severe tissue damage including lymph follicle depletion, splenic nodule atrophy, histiocyte hyperplasia and lymphocyte reductions. Moreover, in situ TUNEL staining illustrated that viral infection leads to severe lymphocyte apoptosis, which might be mediated by viral antigens inducing Fas upregulation. Furthermore, SARS-CoV-2 also triggers macrophages to produce IL-6, a proinflammatory cytokine that directly promotes lymphocyte necrosis. Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue- resident CD169+ macrophages.

Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories

“…We also quantified the genes, surface proteins, and pathway enrichment scores in CD4 + T cells and their correlation with disease severity. Consistent with recent literature (Chen et al, 2020;Mathew et al, 2020), an increase of FAS pathway genes, proliferation genes, activation/effector surface markers CX3CR1, B7-H4, the Th1 differentiation pathway score, and the Type I interferon response gene signature were positively correlated with disease severity ( Figure 3I). By contrast, naïve T cell signatures and the earlyactivation marker CD27 were negatively correlated ( Figure 3I).…”

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

“…Given that SARS-CoV-2 RNAemia is detected, particularly in patients with severe disease 38,42 , it is tempting to speculate that subsequent to CLR-dependent internalization, SARS-CoV-2 could be conveyed by CLR-expressing innate immune cells, and redistributed to permissive tissues where more damage could occur 43 . In accord with this hypothesis, a recent study revealed that SARS-CoV-2 nucleocapsid can be detected in spleens and lymph nodes 44 Finally, defining the differences in glycosylation of S and the variant glycoforms might provide insights into disease severity and spread of the virus in COVID-19 patients. .…”

The Hydra-Headed Coronaviruses: Implications of COVID-19 for Homeopathy

“…60,61 • Spleen and lymphatic dysfunction: direct infection via tissue-resident CD169þ macrophages-which express ACE2, with severe tissue damage. 62 • Dermatological signs: reports are still contentious, while pernio (chilblains, "COVID toes") is currently discussed in the mass media. The American Academy of Dermatology has an open registry to collect data.…”