Dr. Calfee reviewed measurements reported in five studies with a total of more than 900 seriously ill coronavirus patients. Their il-6 levels ranged from normal to slightly higher.
And even when cytokine levels are sky high, as in sepsis, drugs that squelch immune reactions do not help, Dr. Stone said. Failed sepsis studies go back to the late 1980s, he said, when researchers tested etanercept, a drug used to treat autoimmune diseases. It blocks another cytokine, tumor necrosis factor, which, like il-6 is released by white blood cells in sepsis patients.
Etanercept turned out to increase the death rate in those patients.
Dr. William Fischer, a pulmonary and critical care physician at the University of North Carolina, said the idea of a cytokine storm “comes up in every severe viral infection.” Examples include AIDS, Ebola, flu, Lassa fever, SARS and MERS, he said.
But, he said, “it can be difficult to tease apart what drives pathology — whether it’s just the virus or both the virus and the very immune response that is needed to clear the virus.”
“The next step should be a randomized clinical trial,” in which patients are randomly assigned to receive the experimental treatment or not. Instead, Dr. Fischer said, trials, if they started at all, tended to begin after tens of thousands of patients had already gotten the drugs, which muddied the ability to prove safety and effectiveness.
So if not for this cytokine storm, what could be injuring the patients?
Inflammation from a variety of immune system overreactions may play a role, researchers said. One piece of evidence is that the steroid, dexamethasone, which broadly suppresses the immune system, can reduce the death rate.
But il-6 is not the only possible driver of a damaging immune response, Dr. Stone said. Other inflammatory chemicals such as ferritin appear and so does CRP, a protein that is a sign of inflammation.