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Tissue-Specific Immunopathology in Fatal COVID-19.

David A Dorward1,2, Clark D Russell1,3, In Hwa Um4

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|November 20, 2020
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Summary
This summary is machine-generated.

Severe COVID-19 involves significant immune responses independent of the virus itself. These immune dysfunctions, particularly in the lungs and reticuloendothelial system, contribute to organ injury and mortality in the disease.

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Area of Science:

  • Immunopathology
  • Virology
  • Pulmonary Medicine

Background:

  • Corticosteroids improve survival in severe COVID-19, indicating a role for immune responses in mortality.
  • The precise relationship between SARS-CoV-2 presence and detrimental inflammation in severe disease remains unclear.

Purpose of the Study:

  • To investigate SARS-CoV-2 organ distribution and associated inflammatory responses.
  • To explore the links between viral presence, inflammation, and organ damage in fatal COVID-19.

Main Methods:

  • Postmortem tissue analysis from 11 cases of fatal COVID-19.
  • Multiplex PCR, sequencing, and in situ S protein detection for viral mapping.
  • Histological quantification of inflammation across 37 sites and multiplex immunofluorescence for pulmonary immune profiling.

Main Results:

  • Aberrant immune responses were observed, primarily in the lungs and reticuloendothelial system, often not directly correlated with viral load.
  • Inflammation and organ dysfunction did not consistently align with SARS-CoV-2 distribution at tissue or cellular levels.
  • Lung findings included monocyte/myeloid-rich arteritis and increased macrophage/monocyte infiltration; lymphoid tissues showed plasmacytosis and iron-laden macrophages, independent of viral presence.

Conclusions:

  • Severe COVID-19 exhibits tissue-specific immunopathology, with a substantial virus-independent, immune-mediated component driving severe disease.
  • Novel immunopathologic mechanisms are identified, supporting therapeutic strategies targeting macrophage and plasma cell responses.
  • Findings support strategies aimed at modulating immune responses and promoting pathogen tolerance in COVID-19 management.