Studies explain why anti-inflammatory drugs benefit only a few people with severe COVID-19

Review by Emily Henderson, Bachelor of ScienceNovember 16, 2020

The turning point for people with COVID-19 is usually in the second week of symptoms. As most people begin to recover, others find it increasingly difficult to breathe and finish in the hospital. People with lung failure are theorized to be victims of their own excess immune system.

However, new studies from the University of Washington School of Medicine in St. Louis and the St. Jude Children’s Research Hospital in Memphis, Tennessee suggest that uncontrolled immune responses are not a major problem for the majority of hospitalized COVIDs. -19 patients.

Only 4% of the patients who participated in the study had very high levels of immune molecules, which means the so-called “”.Cytokine stormThe rest were inflamed, but not so many for those fighting infections. If anything, COVID-19 patients were less inflamed than an equivalent group of influenza patients.

Survey results published on November 13 Science AdvancesExplain why anti-inflammatory drugs such as dexamethasone are effective in only a small proportion of patients with severe COVID-19, and further research is needed to identify the cause of respiratory failure in patients with COVID-19. I suggest.

One of the first papers published on COVID-19 patients in China reported high levels of cytokines, the so-called cytokine storms, in people in the intensive care unit.

We started looking for it in patients because we wanted to better understand what this cytokine storm looks like, and we were very surprised when we couldn’t find it. It was. We have found that cytokine storms occur, but they are relatively rare even in COVID-19 patients who have respiratory insufficiency and require an artificial respirator.

But now, this idea establishes that respiratory failure of COVID-19 is caused by cytokine storms, and many unproven anti-inflammatory treatments are applied to severe COVID-19 patients to suppress cytokine storms. Given. It worries me because such treatments are unlikely to help most people with COVID-19. “

Philip Mad, MD, PhD, Study COSSenior Author Associate professor of emergency medicine examining patients at Barnes-Jewish Hospital.

Dr. Mad sees the patient at Barnes-Jewish Hospital.

Prior to the pandemic, Mad began investigating the immune response to influenza infection using blood samples obtained with the consent of influenza patients seeking treatment in the emergency department of Burns Jewish Hospital.

In late March, when COVID-19 patients began to become infected with the emergency department, Mad and co-chief author Dr. Ali Ellebedy, an assistant professor of pathology and immunology and an influenza expert, used the same approach. In severe cases of COVID-19, the immune response is unsuccessful.

The researchers analyzed immune cells and molecules in blood samples from 168 COVID-19 patients, 26 influenza patients, and 16 healthy people.

Samples were taken from influenza patients in 2019 or 2020, as well as this year’s COVID-19 patients and healthy controls. They also gathered information about how each patient carried (whether the patient needed intensive care or mechanical ventilation) and whether he or she survived.

In addition to Mad and Elbedy, the research team included co-lead author Paul Thomas and co-lead author Dr. Jeremy Crawford, both of whom included St. Jude and others.

The numbers of inflammatory cells in the blood of COVID-19 and influenza patients were about the same. Seven (4%) of COVID-19 patients showed signs of cytokine storms with very high levels of cytokines, even when compared to other critically ill patients.

The majority of COVID-19 patients with acute respiratory distress were not only free of cytokine storms, but also less inflamed than similarly ill influenza patients.

Several clinical trials have shown that some patients with severe COVID-19 improve steroids, such as dexamethasone, which suppresses inflammation. In a meta-analysis released in September, the percentage of profits was between 2% and 9%. According to Mad, these results are in line with the results of this study.

“4% of people with cytokine storms may be benefiting from steroids in these clinical trials,” Mad said. “I think our work will help explain why steroids help some people, but from our data, it seems that most COVID-19 patients are deficient in steroids. I can’t see. In their bodies, it may not be good for them if you are giving steroids to people who already have a lot of steroids. “

The important thing is to find a way to identify people at high risk for cytokine storms when they first arrive at the hospital. This allows steroid treatment to be adequately targeted at those who are most likely to benefit and least likely to harm.

Researchers ran a panel of routine lab tests, such as measuring blood cell counts and common inflammatory markers, but found no signs of an imminent cytokine storm. They are pursuing a more detailed analysis to find a way to predict who will develop a cytokine storm.

Subjects in a cohort with a “true” cytokine storm phenotype have such outliers immunologically compared to other subjects, and there are significant differences in the multiple immune pathways driving this phenotype. It seems, “said Thomas. “The ability to characterize these pathways that can be rapidly assessed in the clinical setting may help to stratify patients.”

The cause of most cases of respiratory failure in COVID-19 patients remains unknown, as cytokine storms are largely excluded, Mad said.

“In the population we surveyed, 24% died, but only 4% had cytokine storms,” ​​Mudd said. “Most people who died of COVID-19 died without cytokine storms. Severe flu is more inflammatory than severe COVID-19. So what causes their lungs to fail? We? I don’t know yet. We are trying to find out. “