COVID-19: immunopathology, pathophysiological mechanisms, and treatment options

J Pathol. 2021 Jul;254(4):307-331. doi: 10.1002/path.5642. Epub 2021 Mar 25.

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are characterised by a mild, self-limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi-organ failure (MOF). Progression of COVID-19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS-CoV-2 infection and contribute to organ-specific tissue damage. In this respect, dissecting currently available knowledge of COVID-19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune-mediated pathways during SARS-CoV-2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID-19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence-based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID-19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID-19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID-19, and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: acute respiratory distress syndrome (ARDS); angiotensin-converting enzyme 2 (ACE2); autoimmunity; coronavirus disease 2019 (COVID-19); diffuse alveolar damage (DAD); immunopathology; pathology; pathophysiology; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); treatment.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Adaptive Immunity / immunology*
  • Antiviral Agents / pharmacology*
  • COVID-19 Drug Treatment*
  • COVID-19* / pathology
  • COVID-19* / virology
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology
  • SARS-CoV-2 / pathogenicity*
  • United Kingdom

Substances

  • Antiviral Agents