Risk factors for mortality in severe COVID-19: Exploring the interplay of immunomodulatory therapy and coinfection

Anaesth Intensive Care. 2024 Jan;52(1):52-63. doi: 10.1177/0310057X231183451. Epub 2023 Sep 17.


Patients with severe clinical manifestations of coronavirus disease 2019 (COVID-19) present particular diagnostic and management challenges to critical care physicians, including identifying and responding to concurrent bacterial and fungal coinfections. This study evaluates risk factors for in-hospital mortality in patients admitted to the intensive care unit with severe COVID-19 during circulation of the B.1.617.2 (Delta) variant, including the impact of immunomodulators and bacterial and/or fungal coinfection. This retrospective cohort study enrolled patients with severe COVID-19. A Cox proportional hazard ratio analysis identified risk factors for in-hospital mortality. Outcomes were also compared between patients receiving and not receiving immunomodulatory therapy alongside standard care. Ninety patients admitted to the intensive care unit were enrolled. On multivariate analysis, the greatest risk factors for in-hospital mortality were invasive mechanical ventilation (hazard ratio (HR) = 15.27; 95% confidence interval (CI) 3.29-71.0; P < 0.001), elevated body mass index (HR = 1.07 per unit; 95% CI 1.02-1.13; P = 0.007) and older age (HR = 1.53 per decade; 95% CI 1.05-2.24; P = 0.028). Bacterial and/or fungal coinfection occurred at equal frequency in patients receiving and not receiving immunomodulatory therapy. However, in patients receiving immunomodulators, coinfection carried a significantly higher mortality risk (63.0%) compared with those without coinfection (15.4%; P = 0.038). Mortality from severe COVID-19 is significantly higher in older patients and those with elevated body mass index and requiring mechanical ventilation. Immunomodulatory therapy necessitates vigilance towards evolving coinfection in the intensive care setting.

Keywords: COVID-19; SARS-CoV-2; coinfection; critical care; immunomodulation.

MeSH terms

  • Aged
  • COVID-19* / therapy
  • Coinfection*
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunomodulation
  • Retrospective Studies
  • Risk Factors
  • SARS-CoV-2


  • Immunologic Factors

Supplementary concepts

  • SARS-CoV-2 variants