A study in immunocompromised patients found that the corona virus develops mutations while hiding in the lungs, which can help its spread in the rest of the population
Viruses consist of genetic material and an envelope. To penetrate living cells and multiply inside them, they stick to them with the help of a receptor on the shell and use the cell systems. This is how they manage to replicate their genetic material inside the cells and continue to reproduce and infect, until the immune system kicks in.
In every genetic replication, random errors also occur - these are the mutations. As the virus passes from person to person and spreads through the population, it accumulates more and more mutations. Most of these mutations have no clinical significance, but they rarely increase the infectivity, spread and violence of the virus, actually creating a new version of it. Many of the mutations are related to the changes in the proteins that are responsible for the penetration of the viruses into the body's cells.
What is the question? What are the conditions suitable for the spread of COVID-19 over time?
"Viruses have a very high mutation rate. Their genetic material undergoes mutations far more frequently than that of humans or any other organism. This is because their generation time (the time it takes them to replicate their genetic material) lasts one day. In addition, their polymerase - the gene whose function is to carry out the replication process - regularly makes mistakes," notes Prof. Adi Stern, a senior researcher at the Shemunis School of Biomedical Research and Cancer Research in the Faculty of Life Sciences at Tel Aviv University.
Prof. Stern studies the evolution of viruses and focuses on those whose genomes are based on RNA. These viruses are responsible for many diseases, such as corona, influenza, rubella, measles, HIV and hepatitis C. Since the outbreak of the corona epidemic, most of its research has been diverted to the study of COVID-19 - and especially its patterns of change and the mutations it accumulates.
The purpose of Prof. Stern and her team's current research, which was awarded a grant from the National Science Foundation, and which was carried out in collaboration with the Tel Aviv Medical Center (Ichilov), is to understand how the mutations of the corona virus are created, which of them survive and which do not, and what are the appropriate conditions for its spread over time. To this end, the researchers focus on patients with a weakened immune system (for example, blood cancer patients of the leukemia or lymphoma type, AIDS patients and patients who take drugs to suppress the immune system due to an organ transplant or an autoimmune disease) who do not manage to get rid of corona (and other viruses) for a long time.
"During the corona period, many cases of patients with a weakened immune system who had chronic corona were described, some with mild or severe symptoms (for example, breathing difficulties) and some asymptomatic. In fact they carried the virus actively (and not dormant) for months and even more than a year and it was very difficult to treat them. Later they began to speculate that the variants of the corona virus (such as the alpha, beta and omicron) come from these immunosuppressed patients. This is because we found a great similarity between the variants that appeared in them and those that spread throughout the world afterwards", explains Prof. Stern.
The researchers performed genetic sequencing on samples taken from the upper respiratory tract (Bametosh) and lungs of dozens of immunosuppressed patients from Ichilov, and followed them over time. This is how they discovered that many times the virus develops mutations while it is hiding in the lungs. "At the beginning of the study, we saw that in many cases the blood test came out negative and it seemed that the patients had recovered, but after a few weeks the symptoms returned and they underwent another blood test and were found to be positive for the virus. We did not understand why this was happening and if they were reinfected. Later we examined the tests from the lungs and saw that they come out positive while the smear test comes out negative. That is, the virus is not found in the mouth and nose, but it is found in the lungs," says Prof. Stern.
Through the genetic sequencing of the samples over different periods, the researchers discovered that while the virus resides in the lungs, it develops mutations that manage to escape the weakened immune system, reproduces - and returns to the upper respiratory tract with new mutations. These mutations cause a change in its external structure, in a part called a spike (one of the proteins found on top of its envelope), so that it is difficult for antibodies to recognize it. Therefore, the patients had difficulty getting rid of the virus and recovering.
"We saw that the virus develops mutations that help it change the spike and thus escape the immune system and penetrate the cells. First we saw them in chronic corona patients, who are immunosuppressed, and then in the rest of the world," explains Prof. Stern.
It can therefore be understood that the research focuses on the chronic corona patients in order to predict the spread of variants among the general population and to develop drugs against them. "We mainly examined samples from before the micron era, so the question arises as to how much more the virus could change and escape the immune system. In the end, it changes once every six months to a year, and we perform regular monitoring to anticipate the development of a variant that includes dramatic changes (as we have seen recently) and so that we can prepare for it," Prof. Stern concludes.
Life itself:
Prof. Adi Stern, 45, married to Adam and mother of Ali (15), Omri (12) and Maya (6). I like spending time with my family, solving riddles and puzzles of all kinds ("my research is the biggest puzzle I have to solve"), reading a lot (especially at night) and eating fine chocolate.
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