IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection

Virus Res. 2020 Nov:289:198171. doi: 10.1016/j.virusres.2020.198171. Epub 2020 Sep 23.

Abstract

Background: Innate and adaptive immune responses have been evaluated in infected patients with COVID-19. The severity of the disease has been supposed to be associated with some profile not reported with other bacterial and viral pneumonia. We proposed a study in patients with moderate to severe COVID-19 infection to evaluate the interleukin patterns and its role as prognosis factors.

Methods: A prospective cohort with moderate and severe cases of COVID-19 infection from June to July 2020. Blood samples from patients were collected regularly to evaluate IFN-γ, TNF-α, IL-4, IL-6, and IL-10. Clinical, laboratory, radiological data, and outcomes were recorded. The outcome variable was in-hospital death, survival, mechanical ventilation, and admission at the intensive care unit. Data are presented in median and interquartile range [IQR].

Results: We evaluated the Th1 and Th2 responses according to evolution, distinguishing possible predictive markers. The IFN-γ median of 323 pg/mL [IQR 166-570] was found in patients who died and 208 pg/mL [IQR 155-392] in the survival group (p = 0.017). IFN-γ was also higher in the early stages of the disease (394 pg/mL [IQR 229-575] against 162 pg/mL [IQR 117-259], p < 0.001). IL-4 that was increased in late-stage (182 pg/mL [IQR 162-199] against 131 pg/mL [IQR 124-152], p < 0.001) but not associated with mortality. Also, death was also related to male gender (relative risk = 1.5 [95 % confidence interval = 1.1-2.0]).

Conclusion: Our results suggest that the activation of the host immune response between Th1 or Th2 in COVID-19 infection may be related to the final result between discharge or death. This implies an attempt to control cytokines, such as IFN-γ, with combined therapies for clinical treatment.

Keywords: COVID-19; Cytokines; Immune response; Interleukin.

MeSH terms

  • Aged
  • Betacoronavirus*
  • COVID-19
  • Comorbidity
  • Coronavirus Infections / blood
  • Coronavirus Infections / complications
  • Coronavirus Infections / immunology
  • Coronavirus Infections / mortality*
  • Cytokine Release Syndrome / blood
  • Cytokine Release Syndrome / etiology
  • Cytokines / blood
  • Disease Progression
  • Female
  • Hospital Mortality
  • Humans
  • Immunity, Innate
  • Inpatients / statistics & numerical data
  • Intensive Care Units / statistics & numerical data
  • Interferon-gamma / blood
  • Interferon-gamma / physiology*
  • Male
  • Middle Aged
  • Pandemics*
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / mortality*
  • Prognosis
  • Prospective Studies
  • Respiration, Artificial
  • Risk Factors
  • SARS-CoV-2
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Cytokines
  • Interferon-gamma