Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology

Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2.


Human coronaviruses (hCoVs) can be divided into low pathogenic and highly pathogenic coronaviruses. The low pathogenic CoVs infect the upper respiratory tract and cause mild, cold-like respiratory illness. In contrast, highly pathogenic hCoVs such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) predominantly infect lower airways and cause fatal pneumonia. Severe pneumonia caused by pathogenic hCoVs is often associated with rapid virus replication, massive inflammatory cell infiltration and elevated pro-inflammatory cytokine/chemokine responses resulting in acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Recent studies in experimentally infected animal strongly suggest a crucial role for virus-induced immunopathological events in causing fatal pneumonia after hCoV infections. Here we review the current understanding of how a dysregulated immune response may cause lung immunopathology leading to deleterious clinical manifestations after pathogenic hCoV infections.

Keywords: Cytokine storm; Immunopathology; Interferon; MERS-CoV; Monocyte-macrophage; SARS-CoV.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Chemokines / metabolism
  • Combined Modality Therapy
  • Coronavirus / drug effects
  • Coronavirus / physiology*
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / metabolism*
  • Coronavirus Infections / virology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Disease Susceptibility
  • Humans
  • Immune System / cytology
  • Immune System / immunology
  • Immune System / metabolism
  • Immunity, Innate
  • Interferons / metabolism
  • Interferons / pharmacology
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Lung / virology
  • Macrophages / immunology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Phenotype
  • Severity of Illness Index
  • Virus Replication / drug effects
  • Virus Replication / immunology


  • Antiviral Agents
  • Chemokines
  • Cytokines
  • Interferons