US, WASHINGTON (ORDO NEWS) — One of the earliest analyzes of coronavirus patients in China showed that it’s not only the lung-damaging virus that can cause death: an excessive immune response can also make people seriously ill or cause death.
A number of critical patients had high levels of blood proteins – cytokines, some of which can increase immune responses. They include a small but powerful signaling protein called interleukin-6 (IL-6).
IL-6 is a call to arms for the immune system, including macrophage cells. They contribute to inflammation and can damage normal lung cells. The release of these cytokines – the so-called cytokine storm – can also occur with other viruses: for example, HIV.
Thus, an ideal medicine would be one that blocks the activity of IL-6 and reduces the entry of macrophages into the lungs. Such drugs, known as IL-6 inhibitors, already exist to treat rheumatoid arthritis and other diseases. One drug called Actemra (Tocilizumab), manufactured by the Swiss pharmaceutical company Roche, has been approved in China for treating patients with coronavirus, and researchers around the world are actively testing it and other drugs of this type.
Even doctors are not yet clear what exactly affects the organs of infected patients – the virus itself or the reaction of the human immune system. Because of this, doctors cannot determine the best way to treat critical patients.
A number of clinical data suggest that the immune system may play a role in impairing the health and even death of people infected with the new coronavirus. This stimulated the use of steroids for treatment – they help inhibit the body’s immune response to the virus. But some of these treatments act to suppress the immune system as a whole and can undermine the body’s ability to contain viral infections.
“I am most afraid when it is taken to extremes – people use everything they can to turn off the immune response. You cannot destroy the immune system while it is fighting the infection, ”said Daniel Chen, immunologist and chief physician at IGM Biosciences in Mountain View, California.
As patients with coronavirus infest hospitals around the world, doctors wade through streams of incomplete data and preprints that have not been reviewed. They are trying to find ways to help their patients and share experiences on social networks. Some doctors try variations from unsubstantiated treatments in a desperate attempt to save lives.
“[Doctors] observe how patients melt in front of their eyes, and there is very strong motivation to find any therapy that can be effective,” says Kenneth Bailey, an intensive care anesthetist at the University of Edinburgh (UK).
Many clinicians turn to steroids that weaken the immune system more than IL-6 inhibitors, says James Gully, an immuno-oncologist at the National Cancer Institute in Bethesda (Maryland, USA). IL-6 inhibitors can suppress only those immune responses that are regulated by IL-6, without inhibiting other immune responses that can help the body fight COVID-19.
But steroids and some other treatments that work more broadly can significantly reduce the body’s ability to fight infection in general. These drugs will suppress not only macrophages, but also immune cells called CD4 T cells. They are crucial for the initiation of immune responses. Also, steroids suppress CD8 T cells, which are antiviral killers of the body that can destroy infected cells with greater accuracy than macrophages.
Chen notes that although IL-6 levels are high in some acutely ill patients, the viral load is also high, suggesting that the body is still struggling with an active viral infection. “You must assume that there is a consistent antiviral immune response that is important for these patients,” he says. If so, then a decrease in CD4 and CD8 T cells can undermine this response.
Steroids and other immunosuppressants are already being tested for coronavirus in clinical trials. In March, British researchers launched RECOVERY, a randomized clinical trial evaluating the steroid dexamethasone and other possible treatments for COVID-19.
This worries a rheumatologist Jessica Manson from University Hospital (London): data from previous outbreaks caused by related coronaviruses suggest that steroids are of little use and may even delay the time required for patients.
According to Rafi Ahmed, a virologist immunologist at Emory University in Atlanta, Georgia, USA, a combination of viral and immune responses is not uncommon. According to him, the consequences of “hitting” viruses, such as norovirus, from which people get sick almost immediately after infection, are more likely due to the virus itself. Unlike people infected with viruses, such as coronavirus, symptoms do not appear for several days after infection. By then, concomitant damage from the immune response often contributes to the disease.
“It is very difficult to analyze what percentage of this is caused by the virus itself, and what percentage is the immune response. But it’s almost always a combination of the two,” Rafi Ahmed.
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