Clinical and pathological investigation of patients with severe COVID-19

JCI Insight. 2020 Jun 18;5(12):e138070. doi: 10.1172/jci.insight.138070.


Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19.

Methods: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations.

Results: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues.

Conclusions: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.

Keywords: Apoptosis; COVID-19; Infectious disease; Macrophages; Medical statistics; Pulmonology.

MeSH terms

  • Adult
  • Aged
  • Betacoronavirus / isolation & purification
  • Biopsy
  • CD8-Positive T-Lymphocytes
  • COVID-19
  • Chemokine CCL2 / blood
  • Chemokine CCL5 / blood
  • China / epidemiology
  • Coronavirus Infections / blood
  • Coronavirus Infections / diagnosis*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / pathology*
  • Cytokines / blood
  • Disease Progression
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Lung / diagnostic imaging
  • Lung / pathology
  • Lymphocyte Count
  • Lymphopenia / pathology
  • Lymphopenia / virology
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / diagnosis*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / pathology*
  • SARS-CoV-2


  • Chemokine CCL2
  • Chemokine CCL5
  • Cytokines

Grant support

to J. Zhao