A study from Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital in Memphis, Tennessee, suggests that only 4 per cent of Covid-19 patients had the "sky-high levels of immune molecules" that signify a so-called "cytokine storm".
With cytokine storm largely ruled out, the cause of most cases of respiratory failure in Covid-19 patients remains unknown.
The researchers analyzed immune cells and molecules in blood samples from 168 Covid-19 patients, 26 influenza patients and 16 healthy people. The samples were drawn from influenza patients in 2019 or 2020, and from Covid-19 patients and healthy controls this year.
They also collected information about how each patient fared -- whether a patient ended up needing intensive care or mechanical ventilation -- and whether he or she survived, reports Xinhua news agency.
The numbers of inflammatory cells in the blood of Covid-19 and influenza patients were about the same.
Seven or 4 per cent of the Covid-19 patients showed signs of a cytokine storm, with extremely high levels of cytokines even when compared to other severely ill patients.
The majority of the Covid-19 patients with acute respiratory failure not only did not have a cytokine storm, they had less inflammation than influenza patients who were equally ill.
A few clinical trials have shown that some severely ill Covid-19 patients improve on steroid drugs such as dexamethasone that suppress inflammation. The key will be to find a way to identify the people at high risk for a cytokine storm when they first arrive at the hospital.
"The subjects in the cohort with the 'true' cytokine storm phenotype are such outliers immunologically compared to the others, it seems likely that there are significant differences in multiple immune pathways driving this phenotype," said co-senior author Paul Thomas.
"If we can identify features of those pathways that can be assessed quickly in a clinical setting, it could be useful for patient stratification."
"In the population we studied, 24 percent died but only 4 percent had a cytokine storm," said co-senior author Philip Mudd, an assistant professor of emergency medicine who sees patients at Barnes-Jewish Hospital.
"Most people who died of Covid-19 died without a cytokine storm. Severe flu is more inflammatory than severe Covid-19. So what's causing their lungs to fail? We still don't know. We're trying to find out."