The '4 Major Mysteries' of Omicron... Humanity Still Knows Very Little [Reading Science]

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[Asia Economy Reporter Kim Bong-su] Why does the Omicron variant of the COVID-19 virus have such high transmissibility while its fatality rate remains low? What are the perfect ways to block it, and what kind of variant will strike next? On the 25th, the international academic journal Nature reported that scientists worldwide are engrossed in finding answers to these questions about the Omicron variant. Having been discovered only about three months ago, the Omicron variant exhibits very unusual characteristics, and humanity knows very little about it. It is pointed out that these mysteries must be solved for the future development of vaccines and treatments.

◇ Tremendous Transmissibility, Why?

Discovered last November and becoming the dominant strain worldwide in just over three months, the Omicron variant has tremendous transmissibility compared to the existing Delta variant. According to current research results, the Omicron variant has far more mutations in the spike protein that binds to human cells than the Delta variant. This suggests that the virus has evolved to evade antibodies formed through infection or vaccination. However, scientists are focusing their research on the possibility that Omicron may possess something unique that ecologically allows it to have high infectivity while ignoring the human immune system. For example, unlike previous variants, Omicron primarily infects the upper respiratory tract, specifically the nose, where it is widely distributed and releases large amounts of virus with each breath. In fact, research by a team at the University of Hong Kong confirmed that Omicron replicates much faster in the upper respiratory tract than all previous COVID-19 variants.

The research team at Imperial College London also reported that Omicron replicates much faster in nasal cells than the Delta variant. Regarding this, Professor Wendy Barclay of Imperial College London explained, "Previous variants used TMPRSS2 (transmembrane serine protease 2) to cleave their spike proteins to bind to the human cell receptor ACE2 (angiotensin-converting enzyme 2), but Omicron hardly uses TMPRSS2 and instead directly invades vesicles inside the cells." She added, "Since ACE2 is much more abundant than TMPRSS2 in nasal cells, Omicron variants that rapidly replicate in the nose immediately upon inhalation without reaching the lungs or other tissues likely became the dominant strain."

Nasal Epithelial Cells - Mechanism of Coronavirus Infection Elucidated

◇ Is It Really a Weak Strain?

Although the fatality rate has decreased since Omicron became the dominant strain, it has not been clearly established whether it is truly a 'weak strain' or the reasons behind it. This is mainly because most infections occur in individuals who already have antibodies formed from previous infections or vaccinations. However, some experiments conducted on people who had not been previously infected by earlier variants have confirmed the lower fatality rate. A research team at Cleveland Clinic in Ohio investigated symptoms in Omicron-infected patients under five years old who had never been vaccinated and found significantly fewer severe cases requiring emergency room visits, hospitalization, ICU transfer, or mechanical ventilation compared to Delta infections. In South Africa, research results released earlier this year indicated that 25% of the reduction in severe cases and mortality after the spread of Omicron was due to the virus's intrinsic characteristics.

This decrease in fatality rate is analyzed to be because Omicron mainly infects the upper respiratory tract such as the throat and nose, while it is less active in the lower respiratory tract, which can cause pneumonia or breathing difficulties. On the other hand, the proportion of patients complaining of headaches has increased. Additionally, Omicron is also noted for its inability to induce syncytia, a cell fusion that causes pneumonia, unlike other variants.

◇ Find a Treatment

Most monoclonal antibody treatments developed so far have been found to be practically ineffective against Omicron variant viruses. Consequently, scientists are struggling to discover effective treatments for Omicron. In this context, when pathogens such as viruses invade, an enzyme called interferon acts as a 'signal messenger.' Previous variants were able to evade or neutralize the effects of interferon to a considerable extent, but Omicron is presumed to have lost this ability. Scientists are also focusing on T-cells, the body's natural immune cells. Compared to previous variants, Omicron has many more mutations in the spike protein, making it easier to infect human cells, but its ability to evade T-cell surveillance appears to be weakened. Therefore, scientists are trying to identify which parts of Omicron the T-cells recognize and respond to, aiming to utilize this knowledge in vaccine and treatment development.

◇ What Is the Next Variant?

Many scientists do not believe that Omicron is the final variant of the COVID-19 virus. The current Omicron lineage variants may continue to evolve and generate new descendant lineages, or entirely new variants from different lineages may emerge. Especially if the latter occurs, it would demonstrate the virus's tremendous mutability and make response efforts more difficult. Accordingly, experts are studying how the COVID-19 viruses behave and evolve by culturing them in controlled laboratory environments. In fact, a research team at the University of Alabama confirmed that the original COVID-19 virus can increase transmissibility by binding not only to the ACE2 enzyme but also to heparan sulfate, which is present on the surface of all cells. This ability could potentially allow the virus to infect animals and humans more easily through mutations at any time. Professor Jason Kindrachuk of the University of Manitoba in Canada said, "Until recently, researchers were studying the Delta variant, which was the dominant strain before Omicron spread. We only became aware of Omicron at the end of last November, and we still know very little."