Researchers have discovered that in many patients hospitalized with the coronavirus, the immune system is threatened by a depletion of certain essential cells, suggesting eerie parallels with HIV.
The findings suggest that a popular treatment to tamp down the immune system in severely ill patients may help a few, but could harm many others. The research hints that a cocktail of drugs may be needed to bring the coronavirus under control, as is the case with HIV. Growing research points to “very complex immunological signatures of the virus,” said Dr. John Wherry, an immunologist at the University of Pennsylvania.
In May, he and his colleagues posted online a paper showing a range of immune system defects in severely ill patients, including a loss of virus-fighting T cells. In a separate study, they identified three patterns of immune defects, and concluded that T cells and B cells, which help orchestrate the immune response, were inactive in roughly 30% of the 71 COVID-19 patients they examined.
Researchers in China have reported a similar depletion of T cells in critically ill patients, Wherry noted. But the emerging data could be difficult to interpret, he said.
One of the more detailed studies, under review at Nature Medicine, was conducted by Dr. Adrian Hayday, an immunologist at King’s College London. He and his colleagues compared 63 COVID-19 hospitalized patients to 55 healthy people, some of whom had recovered from coronavirus infections.
One of the most striking aberrations in COVID-19 patients, the investigators found, was a marked increase in levels of a molecule called IP10, which sends T cells to areas of the body where they are needed. Ordinarily, IP10 levels are only briefly elevated while T cells are dispatched. But in COVID-19 patients — as was the case in patients with some other coronaviruses — IP10 levels go up and stay up.
That may create chaotic signaling in the body: “It’s like Usain Bolt hearing the starting gun and starting to run,” Hayday said, referring to the Olympic sprinter. “Then someone keeps firing the starting gun over and over. What would he do? He’d stop, confused.”
The result is that the body may be signaling T cells almost at random, confusing the immune response. Some T cells seem undermined, behaving aberrantly. Many T cells apparently die, and so the body’s reserves are depleted — particularly in those older than 40, in whom the thymus gland, the organ that generates new T cells, has become less efficient.
The research suggests that a popular idea for treatment may not help most people. Some patients’ immune systems respond too vigorously to the virus. These overreactions can be quelled with medications that block a molecule called IL-6, another organizer of immune cells. But these drugs have not been markedly effective in most COVID-19 patients, Hayday said. “There clearly are some patients where IL-6 is elevated, and so suppressing it may help,” he said. But “the core goal should be to restore and resurrect the immune system, not suppress it.”