In humans, Omicron seems to be highly infectious, but the symptoms are not as good as other variants. Why is it like this? How does it interact with host cells and the immune system? Answering these questions will help to generate better drugs or vaccines, and provide clues to whether COVID-19 will continue to change and produce new variants. In a recent report, the British magazine Nature solved the four mysteries about Omicron. Why is the communication ability so strong? The rapid spread of Omicron is largely due to its dozens of mutations, which distinguish it from previous variants and enable it to avoid antibodies in the host, especially neutralizing antibodies that bind to the spike protein on the periphery of the virus and prevent the virus from entering the cell. This means that although many people have had extensive immunity against COVID-19's earlier version, there are more hosts for it than the delta. In addition, some characteristics of Omicron itself may also make it highly infectious. In terms of virus transmission, one view is that this variant produces a higher concentration of virus particles in the nasal cavity, so infected people will exhale more virus every time they exhale, but scientists have not reached a consensus in this regard. A study by the team of virologist Michael Chang of the University of Hong Kong on human lung and bronchial tissue supports this speculation. Their data indicate that the replication rate of the upper respiratory system is faster than that of all previous COVID-19 variants. Imperial College virologist Wendy Buckley's team found that Omicron replicated faster in cultured nasal cells than Delta. However, some studies reported that compared with previous variants, hamsters with low immunity had fewer Omicron virus particles in their lungs and were not infectious. Some human studies have shown that the concentration of infectious virus particles produced by Omicron in the upper respiratory tract is the same or lower than that of delta. Buckley believes that the transmission intensity of Omicron may be related to how it enters the cell. The early version of COVID-19 relies on the combination of cell receptor ACE2 and cells, and relies on TMPRSS2 cell enzymes to decompose its spike protein, thus enabling the virus to enter the cell. But Omicron basically gave up TMPRSS2, and the cells swallowed it all, drilling into an intracellular vesicle called endosomes. Buckley said that many cells in the nose produce ACE2 instead of TMPRSS2, which may help Omicron start to function after inhalation before reaching the lungs and other organs commonly expressing TMPRSS2, which may partly explain why Omicron has such strong transmission ability. Why are the symptoms not serious? In terms of hospitalization rate and death rate, Omicron seems to be weaker than the previous variant. But given that many people have a certain degree of immunity through vaccination or previous infection, scientists hope to find out how much of its "weakening" is because many people's immune systems can deal with the virus; To what extent is the virus itself. Scientists at Case Western Reserve University School of medicine in Cleveland, USA, distinguished these two factors by studying the first infection of children under the age of 5 (these children have not been vaccinated). In terms of emergency room visit rate, admission rate or intensive care unit and demand for ventilator, the symptoms of infection with Omicron are lighter than those of delta. In another study, South African scientists analyzed the risk of hospitalization and death in adults in the early stage of Omicron infection. 25% of the factors that reduce the severity of surface infection symptoms are due to the characteristics of the virus itself. What made Omicron's fangs blunt? Michael's team found that although the variant replicated faster in the upper respiratory system, it was less able to replicate in lung tissue. Studies in rodents have found that Omicron infection has less lung inflammation and damage. For humans, Omicron has less ability to multiply or cause damage in the lungs, less cases of severe pneumonia and dyspnea, and more cases of nasal cold. Barkley said that another reason for the decrease in the severity of the symptoms is that it can not fuse individual lung cells into larger syncytial bodies. The previous COVID-19 variant can do so. Some scientists believe that this aggregate can cause symptoms or help the virus spread. How to deal with Omicron? One of the key "weapons" of the human body against pathogens is a molecule called interferon, which is produced when cells detect the invasion of the virus. Interferon will tell infected cells to strengthen their defense and send warning signals to uninfected adjacent cells to strengthen their defense. Previous variants can avoid or inhibit many effects of interferon. Some studies have shown that although Omicron has lost some advantages, it can better resist the effects of interferon. Researchers are also studying the parts of the virus that attract the attention of T cells. Compared with previous variants, the viral proteins recognized by T cells seem to have changed little in Omicron - which is good news because although T cells respond more slowly to repeated threats than antibodies, they are very effective once they start acting, which helps prevent infection symptoms from becoming more serious. Knowing which parts of COVID-19 rarely mutate and activate T cell responses can help scientists develop new vaccines to induce T cells against current and future viral variants. What happens next? The data so far show that Omicron may be highly infectious in the early stage of infection, but when they try to spread beyond the upper respiratory tract or encounter the resistance of interferon, the number of viruses and the ability to infect other cells or people will decline rapidly. Although the severity of symptoms of Omicron infection has decreased significantly, most experts believe that it will not be the final variant. Jesse Brom, an evolutionary virologist at the Hutchinson Cancer Research Center, said that there may be two situations in the future: one is that Omicron continues to mutate to produce a worse Omicron + variant; Another scenario is the emergence of a new variant that is not related to Omicron. Lucy Thorne, a virologist at University College London, said scientists were worried about the second situation, which showed that the virus was highly adaptive and "it had more than one evolutionary choice". Due to dozens of variants, Omicron has more evolutionary space than other variants, and many of its variants are weaker, but bloom everywhere. In addition, scientists suspect that Omicron may penetrate into more species and then spread back to humans, bringing new dangers. (outlook new era)