Description and Analysis of Cytokine Storm in Registered COVID-19 Clinical Trials: A Systematic Review
Khalid Eljaaly, Husam Malibary, Shaimaa Alsulami, Muradi Albanji, Mazen Badawi, Jaffar A. Al‐Tawfiq
Abstract
The purpose of this systematic review was to describe the characteristics of clinical trials that focused on COVID-19 patients with cytokine release syndrome (CRS) and the variability in CRS definitions. Two authors independently searched three clinical trial registries and included interventional clinical trials on COVID-19 hospitalized patients that required at least one elevated inflammatory biomarker. Relevant data, including the type and cutoff of the measured biomarker, oxygen/respiratory criteria, fever, radiologic criteria, and medications, were summarized. A total of 47 clinical trials were included. The included studies considered the following criteria: oxygen/respiratory criteria in 42 trials (89%), radiologic criteria in 29 trials (62%), and fever in 6 trials (18%). Serum ferritin was measured in 35 trials (74%), CRP in 34 trials (72%), D-dimer in 26 trials (55%), LDH in 24 trials (51%), lymphocyte count in 14 trials (30%), and IL-6 in 8 trials (17%). The cutoff values were variable for the included biomarkers. The most commonly used medications were tocilizumab, in 15 trials (32%), and anakinra in 10 trials (24.4%). This systematic review found high variability in CRS definitions and associated biomarker cutoff values in COVID-19 clinical trials. We call for a standardized definition of CRS, especially in COVID-19 patients.