Background A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation. Objectives To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed. Materials and methods Lymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 ( n = 20). Histomorphological characteristics, SARS-CoV‑2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed. Results Lymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8 + T‑cells, and CD11c/CD68 + histiocytosis with hemophagocytic activity. Out of 20 cases, 18 presented with hypoplastic or missing germinal centers with a decrease of follicular dendritic cells and follicular T‑helper cells. A positive viral load was detected by qRT-PCR in 14 of 20 cases, yet immunohistochemistry for SARS-CoV-2 N -antigen revealed positivity in sinus histiocytes of only one case. Gene expression analysis revealed an increased expression of STAT1, CD163, granzyme B, CD8A, MZB1, and PAK1, as well as CXCL9 . Conclusions Taken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B‑cell response, implying an impaired development of long-term immunity against SARS-CoV‑2 in such occasions.
【저자키워드】 immunohistochemistry, Cytokine release syndrome, SARS-CoV‑2, CD8-positive T‑Lymphozyten, Zytokin-Freisetzungssyndrom, Keimzentrum, Immunohistochemie, CD8-positive T‑lymphocytes, Germinal center, 【초록키워드】 COVID-19, immunohistochemistry, immune response, severe COVID-19, Immunity, qRT-PCR, cytokine, CD8, Autopsy, heterogeneity, dendritic cells, Region, Viral, Characteristics, Immunoglobulin, Viral load, cells, plasmablasts, Gene expression analysis, Patient, edema, Mild, CXCL9, Gene expression profiling, Antigen presentation, Stat1, expression, moderate, mechanism, lymph nodes, SARS-CoV‑2, granzyme B, Analysis, Lymph node, class switch, germinal centers, Autopsies, mild to moderate, moderate to severe, regional lymph nodes, immunologic response, Factor, immunoglobulin class, follicular dendritic cells, increased expression, plasmablast, material, CD8A, CD163, CD68, B‐cell, SARS-CoV-2 N, lymph, MZB1, PAK1, CD11c, granzyme, histiocytosis, hypoplasia, plasmacytosis, objective, Result, described, analyzed, include, involved, was performed, follicular, follicular dendritic cell, 【제목키워드】 COVID-19, lung, Lymph node,