The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome

J Transl Med. 2020 Dec 3;18(1):457. doi: 10.1186/s12967-020-02646-9.


Background: Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis.

Methods: Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared.

Results: At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7-22] vs. 4 (0-15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation.

Conclusion: We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. NCT03505281.

Keywords: Acute respiratory distress syndrome; COVID-19; CXCL10; GM-CSF; Immune response; Mechanical ventilation; Pneumonia.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / diagnosis*
  • COVID-19 / immunology*
  • COVID-19 / mortality
  • COVID-19 / therapy
  • Critical Care
  • Female
  • France / epidemiology
  • Humans
  • Immunity, Innate / physiology*
  • Immunophenotyping
  • Lymphocyte Activation / physiology
  • Male
  • Middle Aged
  • Pneumonia, Viral / diagnosis*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / therapy
  • Prognosis
  • Respiration, Artificial
  • SARS-CoV-2 / physiology
  • Severity of Illness Index

Associated data