Study: Respiratory failure in COVID-19 usually not driven by cytokine storm

https://www.eurekalert.org/pub_releases/2020-11/wuso-srf111220.php

 

News Release 13-Nov-2020
Findings indicate anti-inflammatory drugs likely to benefit only a fraction of people with severe disease
Washington University School of Medicine

 

The turning point for people with COVID-19 typically comes in the second week of symptoms. As most people begin to recover, a few others find it increasingly difficult to breathe and wind up in the hospital. It has been theorized that those whose lungs begin to fail are victims of their own overactive immune systems.

A new study from Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital in Memphis, Tenn., however, suggests that an out-of-control immune response is not the main problem for the vast majority of hospitalized COVID-19 patients. Only 4% of patients in the study had the sky-high levels of immune molecules that signify a so-called "cytokine storm." The rest had inflammation, but not a remarkably high amount for people fighting infection. If anything, the COVID-19 patients had less inflammation than a comparable group of influenza patients.

The findings, published Nov. 13 in Science Advances, help explain why anti-inflammatory medications such as dexamethasone benefit only a fraction of people with severe COVID-19, and suggest that more research is needed to identify the causes of respiratory failure in COVID-19 patients.


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A few clinical trials have shown that some severely ill COVID-19 patients improve on steroid drugs such as dexamethasone that suppress inflammation. A meta-analysis published in September placed the percentage who benefit between 2% and 9%. Those results jibe with the findings of this study, Mudd said.

"It could be that the 4% of people who have cytokine storm are the ones who benefit from steroids in those clinical trials," Mudd said. "I think our work helps explain why steroids help some people. But from our data, it doesn't look like most COVID-19 patients have a deficiency of steroids. If you're giving steroids to someone who already has a lot of steroids in their body, that might not be good for them."

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, so that steroid treatment can be appropriately targeted to the ones most likely to benefit and least likely to be harmed. The researchers ran a panel of routine lab tests -- blood cell counts, measurements of common inflammatory markers -- but could not find a signature of an impending cytokine storm. They are pursuing more in-depth analyses to find a way to predict who will develop a cytokine storm.

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"In the population we studied, 24% died but only 4% had a cytokine storm," Mudd said. "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."