Our immune system gets so active in fighting coronavirus that after several days, it produces a so-called cytokine storm that results in potentially fatal organ damage, particularly to the lungs.
A new study by scientists at Washington University School of Medicine in St. Louis suggests that patients become ill because their immune systems can’t do enough to protect them from the virus, sending patients to intensive care units. So, boosting the immune system is the only potential treatment strategy for COVID-19.
Senior investigator Richard S. Hotchkiss, MD, professor of anesthesiology, medicine, and surgery, said, “People around the world have been treating patients seriously ill with COVID-19 using drugs that do very different things. Some drugs tamp down the immune response, while others enhance it. Everybody seems to be throwing the kitchen sink at the illness. It may be true that some people die from a hyperinflammatory response, but it appears more likely to us that if you block the immune system too much, you’re not going to be able to control the virus.”
Scientists are investigating a similar approach to treating sepsis.
Scientists focused on autopsy studies performed by other groups showing large amounts of coronavirus present in the organs of people who died from COVID-19, suggesting that their immune systems were not working well enough to fight the virus. They then compared efforts to inhibit the immune system from fixing a flat tire by letting more air out.
Kenneth E. Remy, MD, the JCI Insight study’s first author, said, “But when we looked closely at these patients, we found that their tires, so to speak, were underinflated or immune-suppressed. To go and poke holes in them with anti-inflammatory drugs because you think they are hyperinflated or hyperinflated will only make the suppression and the disease worse.”
For the study, scientists collected blood samples from 20 COVID-19 patients at Barnes-Jewish Hospital and Missouri Baptist Medical Center in St. Louis. They then employed a test to measure the activity of immune cells in the blood. They compared the blood of those patients to 26 hospitalized sepsis patients and 18 others who were very sick but had neither sepsis nor COVID-19.
They found that the COVID-19 patients frequently had far less circulating immune cells than is typical. Further, the immune cells that were present didn’t secrete normal levels of cytokines — the molecules many have proposed as a reason for organ damage and death in COVID-19 patients.
Instead of trying to fight the infection by further interfering with the production of cytokines, they tried a strategy that has been successful in previous studies they have conducted in sepsis patients.
Hotchkiss and Remy collaborated with researchers in a small study conducted in seriously ill COVID-19 patients who were hospitalized in Belgium. In that study, the COVID-19 patients were treated with a substance called interleukin-7 (IL-7), a cytokine that is required for the healthy development of immune cells.
The study found that IL-7 helped restore balance to the immune system by increasing the number of immune cells and helping those cells make more cytokines to fight infection.
Remy said, “This was a compassionate trial and not a randomized, controlled trial of IL-7. We were attempting to learn whether we could get these immune cells working again — and we could — as well as whether we could do it without causing harmful effects in these very sick patients — and there were none. As this was an observational study involving a small number of patients who already were on ventilators, it wasn’t designed to evaluate IL-7’s impact on mortality.”
Studies focused on boosting immunity and improving outcomes among the sickest COVID-19 patients are just getting underway in Europe, and similar trials are starting in the U.S., including at Washington University.
Hotchkiss said that finding ways to boost the immune response should help not only in COVID-19 patients, but when the next pandemic arises.”
“We should have been geared up and more ready when this pathogen appeared. But what Ken and I and our colleagues are working on now is finding ways to boost the immune system that may help people during future pandemics. We think if we can make our immune systems stronger, we’ll be better able to fight off this coronavirus, as well as other viral and bacterial pathogens that may be unleashed in the future.”