COVID-19 CYTOKINE STORM – What it means and why we need to learn about it.
Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with a wide spectrum of disease severity, with up to 20% of patients developing severe disease and progressing to life-threatening acute respiratory distress syndrome. The immune response in coronavirus infections, including SARS-CoV-2, plays a central role in viral elimination. In addition, emerging evidence suggests that immune dysregulation may contribute to the pathophysiology of severe COVID-19, which exhibits overlapping clinical and laboratory features consistent with a “cytokine storm". This a complex clinical presentation which may be responsible for end-organ damage and mortality observed in this disease entity and consists of hyperinflammation combined with the failure of the immune system to counteract infection with antiviral response mechanisms.
Several pro-inflammatory cytokines, including IL-6, IL-1β and TNF-α, have been demonstrated to be elevated in circulation of COVID-19 patients and to be correlated with disease severity. The clinical presentation of severe COVID-19, laboratory evidence of hyperinflammation, and elevated concentrations of pro-inflammatory cytokines suggests that COVID-19 may be responsive to cytokine-blocking therapies.
Therefore, baseline measurements of cytokines which can be therapeutically targeted have been suggested to guide decisions to administer such pharmaceutical agents. While additional evidence on the clinical utility of this practice and efficacy of cytokine blocking therapies in COVID-19 is eagerly awaited from ongoing clinical trials, the current state on the above subjects will be elaborated on by this course. The course will be regularly updated as new content emerges.
This course will encompass the fundamental aspects of immune response to coronavirus infections, the cellular and pathophysiologic consequences of cytokine dysregulation, and cytokine storm syndrome in the context of coronavirus infections. The changes in the expression of IL-6, TNF-a, IL-1b, and the antiviral cytokines (type I interferon) will be reviewed. Lastly, the anti-cytokine therapies under investigation in COVID-19 and their biologic targets and mechanisms of action will be highlighted. The potential clinical utility of cytokine measurements, the limitations of this practice due to evidence gaps, and pre-analytical and analytical considerations will be covered.
Below are the main learning objectives covered in this course that takes approximately 20 minutes:
- Understand the fundamentals of the immune response in COVID-19 and the pathophysiologic consequences of cytokine release
- Define key terminology commonly used in the context of severe COVID-19 including cytokine storm syndrome, cytokine release syndrome, and secondary HLH
- Identify the molecular targets for specific anti-cytokine therapies under investigation in COVID-19
- Delineate the mechanism of action of tocilizumab, a humanized monoclonal antibody therapeutic against the anti-IL-6 receptor
- Recognize pre-analytical variables and analytical tools that can be used to measure cytokines
In addition to this new course, there are over 60 available courses that span across all disciplines of laboratory medicine; an additional 60 courses will be added over the next couple years. Please visit the website of this program to get more information and to learn how to take advantage of this program.
This post was authored by:
Lusia Sepiashvili, PhD, DABCC
University of Toronto
The Hospital for Sick Children
Melissa R. Snyder, PhD, DABCC
Mayo Clinic College of Medicine
Rochester, MN 55920