Inflammatory proteins, also known as cytokines, play a crucial role in the immune response. If this immune response is too strong, a phenomenon known as "cytokine storm," it can cause harm to the patient. It has been thought that a cytokine storm contributes to disease severity in patients with COVID-19. Following the measurement of several important cytokines in patients with COVID-19 and various other severe diseases, researchers at Radboud University Medical Centre now show that COVID-19 is not characterised by a cytokine storm. This may have consequences for the treatment of these patients, the researchers write.
The cytokine storm in COVID-19 patients is not clearly defined. In many cases, different cytokines are evaluated and no comparison has been made with other diseases. Therefore, uncertainty and doubt exists concerning the cytokine storm in these patients.
Researchers from the Intensive Care (IC) department at Radboud University Medical Centre have now measured the concentration of three essential cytokines in the blood of patients admitted to the IC with several distinct conditions. They performed these measurements in patients with COVID-19 who met the criteria for a severe acute respiratory infection (ARDS), patients with bacterial septic shock (with and without ARDS), and patients who had been admitted to the IC after a cardiac arrest or severe trauma. The cytokines were measured using the same methods for each of the groups of patients.
In the above-described five patient groups, the concentration of tumour necrosis factor alpha (TNF-alpha) and interleukins 6 and 8 (IL-6, IL-8) was measured. The results were remarkable. Researcher Matthijs Kox: "The level of cytokines was significantly less elevated in COVID-19 patients than in patients with septic shock and ARDS. Compared to patients with septic shock without ARDS, so without severe pulmonary disease, patients with COVID-19 also displayed markedly lower levels of IL-6 and IL-8. The cytokine concentrations in COVID-19 patients were similar to those in IC patients with trauma or cardiac arrest, conditions that are not noted for a cytokine storm."
The results from this study show that COVID-19 is not characterized by a cytokine storm. Professor of intensive care medicine Peter Pickkers: "The severe disease observed in critically ill COVID-19 patients is therefore not explained by strongly elevated levels of inflammatory proteins in the blood. This means that critically ill COVID-19 patients likely will not benefit from specific anti-cytokine therapies."
Abstract
An abnormally strong proinflammatory response known as “cytokine storm” may play an important role in the pathophysiology of coronavirus disease 2019 (COVID-19), although cytokine storm remains ill defined.1 Sinha and colleagues2 reported that although IL-6 levels are elevated in severe COVID-19, they are lower than levels usually observed in (non–COVID-19) acute respiratory distress syndrome (ARDS). However, this comparison is limited by the use of different assays, which are not well standardized.3 We compared cytokine levels in critically ill patients with COVID-19 vs levels in patients with other critical illnesses.
Authors
Matthijs Kox, Nicole JB Waalders, Emma J Kooistra, Jelle Gerretsen, Peter Pickkers
[link url="https://www.radboudumc.nl/nieuws/2020/bestaat-de-covid19-cytokinestorm"]Radboud University Medical Centre material[/link]
[link url="https://jamanetwork.com/journals/jama/article-abstract/2770484"]JAMA abstract[/link]