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A scoping review of the pathophysiology of COVID-19

Paul E Marik1,2, Jose Iglesias3,2, Joseph Varon4,2

  • 1Division of Pulmonary and Critical Care Medicine, 6040Eastern Virginia Medical School, Norfolk, VA, USA.

International Journal of Immunopathology and Pharmacology
|September 27, 2021
PubMed

Insights

Severe COVID-19 involves complex pathogenesis, including pulmonary inflammation, endothelialitis, and a procoagulant state. Understanding these mechanisms is crucial for developing effective treatments and prevention strategies for coronavirus disease 2019.

Area of Science:

  • Pathology
  • Immunology
  • Virology

Background:

  • COVID-19 presents as a complex and heterogeneous disease.
  • A comprehensive understanding of COVID-19 pathogenesis is currently lacking.
  • Effective prophylactic and treatment strategies require a deep understanding of disease mechanisms.

Purpose of the Study:

  • To provide a clinical overview of the major pathogenetic mechanisms leading to severe COVID-19.
  • To synthesize findings from clinical, proteomic, genomic, and autopsy studies.
  • To elucidate the multifactorial nature of severe COVID-19.

Main Methods:

  • Review of clinical data.
  • Analysis of proteomic and genomic studies.
  • Examination of autopsy findings.

Main Results:

  • Severe COVID-19 is characterized by pulmonary macrophage activation syndrome with uncontrolled inflammation.
  • Complement-mediated endothelialitis and a procoagulant state with thrombotic microangiopathy are key features.
  • Platelet activation, mast cell degranulation, and auto-antibodies contribute to hyper-inflammation and end-organ damage.

Conclusions:

  • Severe COVID-19 results from the interplay of inflammation, endothelial damage, and thrombosis.
  • Identifying these pathogenetic pathways is essential for therapeutic development.
  • Further research into these mechanisms will guide the management of severe coronavirus disease 2019.

Keywords:
COVID-19NETosisautopsycomplementmacrophage activationmicro-vasculitispathogenesisserotonin

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