How kills COVID-19? Doubts as to what exactly affects the human organs — the virus itself or the response of the infected immune system — prevent doctors from finding the best ways to treat patients suffering from severe coronavirus.
Clinical evidence suggests that the immune system plays a role in making people infected with the new coronavirus weaken and die. This has given impetus to the use of drugs such as steroids, which curb such a powerful immune response. But some drugs suppress the immune system, and this raises concerns that such drugs actually interfere with the body’s ability to cope with a viral infection.
“What scares me the most is that it goes to extremes when people clutch at anything in an attempt to turn off the immune response,” says immunologist Daniel Chen, a medical director at AJ, a biotechnology company in California, California. Em Biosciences ”(IGM Biosciences). “You can simply disable the immune system when it fights the infection.”
–
The pursuit of medicine
Today, when coronavirus-infected people overwhelm hospitals around the world, doctors are shoveling mountains of incomplete data and scientific articles that have not yet received authoritative reviews, trying to find an opportunity to help patients and share their experience on social networks. Some doctors, in a desperate attempt to save the lives of patients, resort to combinations of untested medications and treatments.
“People see patients fade before their eyes, and they have a very strong desire to grab onto any medicine that they think is effective,” says Kenneth Bailli, a resuscitation anesthetist at the University of Edinburgh in Britain. “I have the same desire when I stand at the patient’s bed and feel powerless.”
–
Thus, an ideal counterweight should be a drug that blocks the activity of interleukin-6 and reduces the influx of macrophages into the lungs. Such drugs, known as IL-6 inhibitors, are already used in the treatment of rheumatoid arthritis and other diseases. One of them is called Actemra (tocilizumab), and it is produced by the Swiss pharmaceutical company Roche. In China, it is approved for the treatment of coronavirus infections, and scientists around the world are hastily testing Actemra and other drugs of this type.
Immunity issues
But in the world, this medicine is simply not enough, and many physicians use steroids that actively weaken the immune system, says immuno-oncologist James Gulle, who works at the National Institute of Oncology in Bethesda, Maryland. IL-6 inhibitors can suppress only those immune responses that are controlled by IL-6, which allows other immune responses that help the body fight COVID-19 to continue. However, steroids and some other drugs that have a more general effect can significantly weaken the body’s ability to fight infection. They suppress not only macrophages, but also immune CD4 T cells, which are very important for triggering an immune response, as well as CD8 T cells, which are antiviral killers in the body that can destroy infected cells much more precisely than macrophages. “When things really get serious, they add steroids,” says Galli. “I’m a little worried about the direction in which some doctors are moving.”
Chen notes that although the level of IL-6 in some critically ill patients is high, the concentration of the virus in the blood is also very high, which suggests that the body is still struggling with an active viral infection. “We must proceed from the fact that the antiviral immune response continues, which is very important for such patients,” he says. If so, then a decrease in the number of T cells of CD4 and CD8 may weaken this response.
Steroids and other drugs to suppress immunity are already undergoing clinical testing for the fight against coronavirus. In March, British scientists launched a study called RECOVERY (recovery), which is a randomized clinical trial of a steroid dexamethasone and other drugs for the treatment of COVID-19. This is alarming for a rheumatologist Jessica Manson of the University College London Hospital. Data on previous epidemics caused by related coronaviruses suggest that steroids are of little use, and they can even increase the time it takes a patient to get rid of the virus, she notes. The RECOVERY study may lead to the fact that these drugs will be given to patients before they become seriously ill, and they will have no other choice.
Complex therapy
Combined lesions from the virus and immune response are common, says viral immunologist Rafi Ahmed, who works in Atlanta at Emory University. Exposure to viruses such as norovirus, which works on the fly-and-fly basis and causes a person’s illness almost immediately after infection, is likely caused by the virus itself, he says. However, in people who become infected with coronavirus, symptoms appear only a few days after infection. By then, collateral damage from the immune response often already exacerbates the disease.
“It’s very difficult to determine exactly what percentage is caused by the virus itself and what kind of immune response,” Ahmed says. “But it’s almost always a combined effect.”
–
Ahmed hopes that in the absence of an answer to this question, scientists will conclude that complex therapy is needed, say, with the use of an inhibitor of IL-6, which does not completely inhibit the immune system, in combination with an antiviral drug that directly affects the virus. Other drugs that affect the immune system are tested, including Anakinra, which acts on the signal protein IL-1 and can weaken some immune responses without interfering with CD4 and CD8 T cells, Chen says.
However, Bailey notes that now in the treatment of people with coronavirus steroids are already used very widely, and therefore it is important to collect data on the results. He is also worried about the suppression of the immune response in patients with COVID-19, but he emphasizes that such practice can still be of some benefit.
“The only responsible way is to use them as part of a randomized clinical trial,” says Bailey. “We simply have no other way of knowing if such treatment works.”
–
–
