COVID Carriers
The explanation of a large number of asymptomatic patients has been found
Maria Nedyuk, Izvestia
A large number of asymptomatic carriers of COVID-19 may be associated not with good immunity, but with tolerance to infection. This conclusion was reached by scientists from China and the USA (Chang et al., Host tolerance contributes to persistent viral shedding in COVID-19 // EClinicalMedicine 2020).
With tolerance to the virus, the body gets along well with the pathogen due to a weak protective reaction. Such infected people feel well and may not even suspect about their illness. However, the virus will live in the host body for a long time and be released into the environment. A similar phenomenon has been described for tuberculosis, cholera and other infections. So far, this is only a hypothesis, the researchers emphasize. But the theory requires further study, as it opens up a lot of new opportunities for clinicians.
Get infected and not get sick
The phenomenon of asymptomatic COVID-19 is studied by scientists around the world. The prevailing theory is that the immune system of such people fights the virus so effectively that they do not get sick. However, some scientists believe that an aggressive immune response and the release of antibodies is only part of the explanation of why people become infected, but they do not have symptoms of COVID–19. There is a phenomenon known as disease tolerance. This is a condition of the body in which the immune system perceives a foreign antigen as its own and does not try to reject it. As a result, the body does not fight the disease, inflammatory and protective processes do not start, so the patient has no symptoms.
The cases of three patients with tolerance to coronavirus were recently described by specialists of the College of Pulmonary Medicine and Intensive Care at the Chinese General Hospital in Beijing. All three have confirmed COVID-19 by PCR test. They were admitted to hospitals with a persistent viral presence that was observed for at least 50 days. All three were elderly – from 50 to 60 years old.
"Surprisingly, all three patients had comorbidities, including hypertension and diabetes, both of which are a well-established risk factor for the severity of the disease and death due to COVID-19," the article says. "Despite these underlying diseases, patients had minimal or no symptoms, but the viral presence persisted for extended periods of time. We assume that due to the high tolerance to the virus, these patients developed a limited antiviral and anti-inflammatory response of the host, which led to minimal or no symptoms. At the same time, the limited antiviral and anti–inflammatory response of the host allowed the virus to persist for long periods of time," the doctors concluded.
Perfect inflammation
Earlier, scientists from the United States also expressed their opinion on tolerance to coronavirus. Tolerance takes different forms depending on the infection, according to their article in Scientific American. For example, when infected with cholera, which causes watery diarrhea (rapid death due to dehydration is possible), the body can activate mechanisms that maintain the balance of fluid and electrolytes. During other infections, a person is able to change the metabolism or activate intestinal microbes.
Researchers consider asymptomatic infections as evidence that people have a tolerance to diseases. For example, this is true for many of the 1.5 billion people around the world who live with helminths in the intestines.
– Despite the fact that these worms are very large organisms, they migrate through your tissues and cause damage, many people have no symptoms. They don't even know they're infected," Ira King, professor of immunology at McGill University, is quoted as saying by the publication.
The situation with COVID-19 may be similar to tuberculosis: most of the patients are carriers of infection without visible symptoms.
"With things like coronavirus, I think it's going to be very similar to tuberculosis, when you need the perfect amount of inflammation to control the virus and not damage the lungs," Andrew Olive, an immunologist at the University of Michigan, told Scientific American.
Biological balance
Initially, the phenomenon of tolerance was found in plants, for them it is well characterized. In recent years, it has become clear that in the case of human infections, this phenomenon also plays an important role. Bacterial and viral respiratory infections occupy a special place among such diseases, Acting Director of the Institute of Biomedical Systems and Biotechnologies of Peter the Great St. Petersburg Polytechnic University (SPbPU) Andrey Vasin told Izvestia.
– The body tries to neutralize the consequences of meeting with the pathogen as quickly as possible. To do this, two strategies are used: to quickly and effectively get rid of the pathogen itself so that it does not have time to start pathological processes, or to reduce the damage or changes caused by infection. In the second case, they talk about the formation of tolerance to the disease," the expert explained. "Under certain conditions, these two strategies may come into conflict with each other. For example, an immune response when trying to get rid of a pathogen causes more harm to the body than the pathogen itself. On the other hand, anti-inflammatory reactions aimed at the emergence of tolerance to infection can lead to suppression of immunity and the inability of the body to resist infection.
Therefore, the delicate balance between these two processes ultimately ensures the successful confrontation of the disease by the body, Andrei Vasin believes.
– An asymptomatic carrier is an example of a kind of biological equilibrium, in which the host organism is unable to remove the parasite, and the parasite is unable to overcome the body's defenses and cause illness, – an infectious disease specialist, an employee of the scientific and clinical department of the MGC AIDS and the International Educational and Methodological Center for Human Virology of the RUDN Medical Institute told Izvestia Elena Belova. – Under the action of the body's defenses, the pathogen sooner or later dies, and the carrier stops.
Tolerance and mutations
There is another phenomenon that explains people's immunity to coronavirus, scientists believe. People with certain mutations in their genes cannot get infected with coronavirus, Rospotrebnadzor said. "Scientists have found out that polymorphisms (mutations) in the gene encoding the ACE2 protein, which the coronavirus uses to penetrate the cells of the respiratory tract, can facilitate or hinder the penetration of the virus into cells," the ministry said. However, in this case we are talking about the impossibility of infection, and not about asymptomatic carrier.
– Immunity to the pathogen is not just a milder course of the disease, – said Stanislav Otstanov, acting head of the laboratory for the analysis of public health indicators and digitalization of healthcare at MIPT (a university participating in the project to increase the competitiveness of education "5-100"), in a conversation with Izvestia. – For example, as a result of a rare CCR5-Δ32 mutation, people become immune to HIV. Moreover, it was the transplantation of hematopoietic stem cells from a donor with a similar mutation that led to the fact that Timothy Ray Brown, better known as the "Berlin patient", became the first person cured of HIV.
In the case of COVID-19, it is still unclear what determines the outcome of the disease, scientists emphasize. And the point here is not so much in the virus as in the infected person's body. If we talk about tolerance, then the phenomenon itself requires further study, and it is premature to draw final conclusions yet.
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