Histomorphological patterns of regional lymph nodes in COVID-19 lungs
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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Enthalten in: |
Der Pathologe - 42(2021), 2 vom: 11. März, Seite 188-196 |
Sprache: |
Deutsch |
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Weiterer Titel: |
Reaktionsmuster der lokoregionären Lymphknoten im Abflussgebiet von COVID-19-Lungen |
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Beteiligte Personen: |
Haslbauer, Jasmin D [VerfasserIn] |
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Links: |
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Themen: |
CD8-positive T‑lymphocytes |
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Anmerkungen: |
Date Completed 10.03.2021 Date Revised 21.04.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1007/s00292-021-00914-z |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM321357655 |
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520 | |a 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 | ||
520 | |a OBJECTIVES: To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Review | |
650 | 4 | |a CD8-positive T‑lymphocytes | |
650 | 4 | |a Cytokine release syndrome | |
650 | 4 | |a Germinal center | |
650 | 4 | |a Immunohistochemistry | |
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700 | 1 | |a Tzankov, Alexandar |e verfasserin |4 aut | |
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