Histopathology and genetic susceptibility in COVID-19 pneumonia

Eur J Clin Invest. 2020 Jul;50(7):e13259. doi: 10.1111/eci.13259. Epub 2020 Jun 27.


Background: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission.

Aims: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease.

Materials and method: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors.

Result: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension.

Discussion: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects.

Conclusion: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.

Keywords: COVID-19; genetics; pulmonary histopathology.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus
  • COVID-19
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / genetics
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology*
  • Cytokine Release Syndrome / immunology
  • Diabetes Mellitus / epidemiology
  • Edema / pathology*
  • Fibrosis
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • Humans
  • Hypertension / epidemiology
  • Inflammation / immunology
  • Inflammation / pathology*
  • Influenza, Human / pathology
  • Obesity / epidemiology
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / genetics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology*
  • Polymorphism, Genetic
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / pathology*
  • Respiratory System / pathology
  • Risk Factors
  • SARS-CoV-2
  • Serine Endopeptidases / genetics
  • Severe Acute Respiratory Syndrome / pathology
  • Thrombosis / pathology*


  • HLA Antigens
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human