Antiviral immune response is suppressed in COVID-19 patients compared to influenza patients

Review by Emily Henderson, Bachelor of ScienceNovember 16, 2020

Most adults with moderate to severe COVID-19, rather than life-threatening hyperinflammation, have a suppressed viral immune response compared to adults with influenza, another viral respiratory infection.

The St. Louis Children’s Research Hospital in St. Louis and the University of Washington School of Medicine have led a study suggesting that most COVID-19 patients are not candidates for treatment with steroids such as dexamethasone.The study will be displayed today Science Advances..

In this study, less than 5% of COVID-19 patients, including some of the most ill, showed a life-threatening hyperinflammatory immune response. Cytokine storm syndrome. Cytokines are small proteins secreted by blood cells that help regulate the immune response and cause inflammation.

Cytokine storms occur when excessive or abnormally regulated cytokine production causes hyperinflammation and tissue damage. Dexamethasone and other steroids are prescribed to treat cytokine storms, but the drug can be counterproductive in patients whose immune response is already suppressed.

Cytokine storms have been proposed as a cause of respiratory failure in COVID-19 patients.

We identified a subset of COVID-19 patients with a widely up-regulated set of cytokines that are characteristic of cytokine storms. But overall, the average person with COVID-19 was less inflamed than the average person with influenza, even in patients with moderate to severe illness. “

Dr. Paul Thomas, Collaborative Research Author, Faculty of Immunology, St. Jude Children’s Research Hospital

“The findings suggest that treatments that suppress inflammation may only be effective in a small number of patients with an inflammatory profile,” Thomas said. He of the University of Washington School of Medicine, Ali Ellebedy, Ph.D. , And Philip Mudd, MD, Ph.D. Is the corresponding author of this study.

Researchers say that what is needed is a fast, reliable, and inexpensive test to measure cytokines and identify patients who are most likely to benefit from immunosuppressive treatment.

Mad, a scientist and emergency physician treating patients with COVID-19 at Barnes-Jewish Hospital in St. Louis, said: “Directing immunosuppressive therapy to a small subset of COVID-19 patients with an overactive immune response is the only way to know if these approaches will ultimately help.”

Immune response: COVID-19 vs. influenza

It is also necessary to better understand the immune response to COVID-19, including the causes of respiratory failure reported in as many as 8% of patients.

Researchers perform it in this report, which derives from one of the largest and most comprehensive comparisons of human immune response to SARS-CoV-2, the virus that causes influenza and COVID-19. I tried. Unlike COVID-19, the immune response to influenza has been studied for decades and is better understood.

The study included 168 adults with COVID-19, 26 adults with influenza, and 16 healthy volunteers. Over 90% of COVID-19 patients were hospitalized and about half were hospitalized in the intensive care unit. Twenty-three percent of those hospitalized died. More than half of influenza patients were hospitalized, 35% died in the ICU and 8% of hospitalized patients died.

To understand the immune response, researchers measured a variety of immune cells and factors, including 35 different cytokines. Seven COVID-19 patients, or 4%, met the study definition of cytokine storms. This means that more than half of the 35 cytokines were significantly elevated compared to the patient average. Statistically, elevation was defined as at least two standard deviations from the mean.

Patients with cytokine storm syndrome had individual cytokine levels 10 to 100 times higher than average. However, when researchers included age and other factors, COVID-19 patients had lower overall cytokine levels than influenza patients.

What if it’s not a cytokine storm?

“The absence of hyperinflammation in most COVID-19 patients does not mean that they are less ill,” said Dr. Jeremy Chace Crawford, co-lead author of St. Jude Immunology. “In most cases, the disease is not caused by widespread hyperinflammation due to cytokine storms, but has important implications for the development of generalized COVID-19 therapies.”

The analysis revealed that the antiviral immune response was significantly suppressed in COVID-19 patients compared to influenza patients. In addition to cytokine measurements, researchers analyzed cytokine transcription in individual blood cells of influenza patients, COVID-19, and healthy volunteers. COVID-19 was associated with a significant reduction in the production and response of type I and type II interferons, which are cytokines that play a central role in the antiviral immune response.

Researchers have also found evidence that SARS-CoV-2 alters pathways that control the immune response and promotes steroid production by patients.

“Our results suggest that most COVID-19 patients already produce high levels of glucocorticoids before treatment, which probably leads to the weakened immunity seen in most patients.” Said Thomas. “These patients may need treatment to boost their immune response in order to knock down the virus.”