Where do coronavirus variants come from?

Evolutionary mapping in chronic corona patients Reveals the way to the formation of a variant * In immunocompromised patients, a chronic disease of corona sometimes develops. The study found that the damaged immune system of these patients fails to eliminate the virus, which, on the other hand, develops over time mutations that confer resistance to antibodies and are more contagious

A new study by Tel Aviv University estimates that the many variants of the corona are created in chronic corona patients who suffer from severe damage to the immune system. The researchers estimate that those chronic patients suffer from little activity of the immune system in the lung area, and the variants take advantage of this to escape the weak immune system and reside in the body for a long time. However, according to the researchers, it is likely that the ability of the virus to survive and multiply in the patient's body without limitation leads to the fact that there is not necessarily an advantage to developing mutations that encourage transmission from person to person, and therefore the formation of a variant that spreads rapidly is a rare event. But, when the number of infections around the world reaches an extremely high number, that rare event becomes a reality.

The research was conducted under the leadership of Prof. Adi Stern and PhD student Shari Harari from the Shemunis School of Biomedical and Cancer Research, Faculty of Life Sciences at Tel Aviv University. The study was published in the prestigious journal "Nature Medicine".

Prof. Stern explains that since the outbreak of the corona virus, the mutation rate of the virus has created many doubts. On the one hand, in the first year of the epidemic, a relatively slow rate of mutation accumulation was observed. On the other hand, since the end of 2020, variants that are characterized by a large number of mutations, much more than expected, occasionally "jump" into our lives. Various hypotheses in the world of science about the relationship between chronic corona patients and the rate of mutation formation have arisen, but the issue has not yet been proven. In the new study, Prof. Stern and her laboratory team illuminate part of the complex puzzle and try to answer the scientific question of how variants are created.

Prof. Stern explains: "Corona is characterized by the fact that in every population there are people who, when infected, will become chronic corona patients. In these patients, the virus remains in their body for a long period of time and they are at a high risk of recurrent disease. In all the cases observed so far, these were patients with a weakened immune system, when one of the arms of the system is damaged and does not function. In evolutionary terms, these patients constitute an 'incubator' of viruses and mutations - the virus stays in their body for a long time and manages to adapt to the immune system and the treatments the patient receives by accumulating different mutations.

The study included an examination of chronic corona patients at the Ichilov Hospital, the Tel Aviv Medical Center named after Sorasky. According to Prof. Stern, the results indicate a complex picture: on the one hand, no direct connection was found between drug treatment and the development of the variants. On the other hand, it was discovered that it is the patients' defective immune system that creates pressure on the virus to change. In fact, the researchers found that there are chronic patients who showed a pattern of apparent recovery, and then the disease returned. In all those patients, the virus came back in a mutant form, meaning that the recovery was not complete, which is partially reminiscent of the mode of action of the HIV virus after poor drug treatment.

In an in-depth examination of certain patients, the researchers discovered that when there is a pattern of apparent recovery (which is based on negative swab tests sampled from the pharynx and nose), the virus actually continues to exist in the lungs. And so the researchers suggested that the virus accumulates healthy mutations, then "climbs" back to the upper respiratory areas.

At the same time, as mentioned, the picture is complex: the researchers discovered that although the chronic patients are characterized by different combinations of mutations that allow evasion of antibodies, this is not the whole picture. Precisely known mutations that allow the virus to be transmitted from person to person effectively - those mutations have never been observed in the virus that infects the chronically ill. This is a happy finding - it indicates that not every variant that is created in the bodies of chronic patients will become a variant capable of spreading in the general population.

Prof. Stern: "In deep thought, these phenomena can be explained in the following way: the variant was able to settle in a chronic patient suffering from damage to the immune system, it actually found a 'comfortable' body in which it can stay and exist for a long time. Under these conditions, the virus improves attitudes within the patient's body, and is "unmotivated" to pass to another person. It is possible that even mutations that allow transmission to other people come 'at the expense' of evading antibodies, so the virus will actually give up mutations of this type in favor of mutations to evade the immune system of the patient it infects."

Prof. Stern concludes: "The corona is revealed in its complexity and poses many challenges to the scientific community. I believe that our research was able to discover a missing layer in the big picture, and allow an opening for further research that will discover the origin of the various variants. The study emphasizes the importance of protecting those immunosuppressed patients, who are at great risk from the corona disease itself, and who may be a reservoir for the formation of the next variant."

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