Fighting against Omicron: Understand your opponent and prepare actively

Why is Omicron so contagious?

Since it was first reported in November 2021, the Omicron variant has rapidly swept the world with its super strong transmission ability. In January 2022, it replaced the Delta variant and became the dominant variant raging around the world, becoming a new starting point for the epidemic.

As the fifth variant of concern (VOCs) announced by the WHO after Alpha, Beta, Gamma and Delta, the Omicron variant has significant differences in genomic, biological and epidemiological characteristics from previous variants. It has an amazing ability to spread and super antibody escape ability , which is also an important reason why most of us cannot escape Omicron infection.

1 Amazing Mutation Ability

As we all know, the new coronavirus is an RNA virus, and RNA viruses usually adapt to the ever-changing living environment with a high mutation rate . Combined with its frequent genetic recombination, the new coronavirus has evolved into thousands of variants since the outbreak. The Omicron variant and its subspecies are "unique", and their super evolutionary advantages are fully demonstrated in genomics, biology, and epidemiological characteristics.

Compared with the Wuhan-Hu-1, the first coronavirus genome isolated in 2019, Omicron has a large number of mutations in the spike protein. Studies have shown that the original Omicron variant (BA.1) has 30 amino acid substitutions, 3 in-frame deletions, and 3 amino acid insertions (ins214EPE) in the spike protein S, far exceeding the 6 amino acid substitutions of the Delta variant. Fifteen of these mutations are located in the receptor binding domain (RBD) of the spike protein, which is the region where the virus binds to receptors on host cells and neutralizing antibodies, and has great biological significance for the spread of the virus and immune escape.

Figure 1 Mutation regions of two novel coronavirus variants (red) Left: Delta Right: Omicron

Image source: COVID-19 Genomics UK Consortium

Mutations may enhance the virus's ability to bind to receptors or escape and bind to neutralizing antibodies, thereby gaining an evolutionary advantage.

According to the artificial intelligence model, the affinity of the S protein of the Omicron variant for binding to the receptor is 13 times that of the original strain and 2.8 times that of the Delta variant.

Structural analysis of the S protein shows that the enhanced antibody escape ability caused by the mutation while maintaining strong binding ability to the receptor is the molecular basis for Omicron to spread rapidly around the world.

Furthermore, Omicron did not develop from earlier VOCs but evolved in parallel in the dark and spread rapidly around the world in a divergent and diverse lineage.

BA.1 BA.2 BA.3 BA.4 BA.5

As of November 6, 2022, the WHO's analysis of the genetic sequences of the coronavirus worldwide showed that the BA.5 variant dominates the world, with a prevalence rate of 72.1%.

Phylogenetic analysis (Figure 2) shows that the rate of evolution and mutation of Omicron has far exceeded that of the original strain. The evolution and mutation of Omicron is still continuing, and new dominant mutants will continue to replace it.

Figure 2 Time-scale phylogenetic tree of global SARS-CoV-2 genomes, produced by Nextstrain software

2. Super strong antibody escape ability

In addition to its enhanced ability to bind to receptors, another important reason why Omicron has extremely strong transmission ability is its ability to escape the immune barriers established by vaccines and previous infections.

Studies have shown that the protection provided by previous infection history with other variants against Omicron is relatively limited. The protection provided by previous infection history against Alpha, Beta and Delta variants is 90.2%, 85.7% and 92.0% respectively, while against Omicron variant it is only 56.0%.

This is because the new coronavirus vaccine we are currently using mainly targets the S protein, which has a corolla structure and binds to host cells in the form of a trimer. Each trimer has a receptor binding domain, like a small open "hand", grabbing human angiotensin-converting enzyme 2 (ACE2) and anchoring the virus to the host cells.

In March 2022, a study published in Molecular Cell found that mutations caused the shape of the "hand" of the Omicron spike protein to change. The "hand" is no longer open, but binds to the receptor in a "curled" posture, hiding the area recognized by antibodies. As mentioned earlier, the large number of mutations in the S protein of Omicron makes part of the S protein unrecognizable by antibodies, which makes Omicron have a strong ability to escape humoral immunity.

However, the cellular immune memory established by the vaccine can still respond to Omicron, playing an important role in reducing severe illness and death . In addition, more and more data suggest that boosting immunization is important for further reducing severe illness and mortality associated with Omicron infection .

Data from Hong Kong, China show that although the inactivated vaccine widely used in my country provides lower protection than the mRNA vaccine for high-risk people over 60 years old after two doses, after three doses, the overall effectiveness of the two vaccines in preventing severe illness or death can reach more than 97%.

Therefore, although Omicron's powerful immune escape ability can break through the immune barriers established by previous infections and vaccines, the cellular immune memory established by the vaccine can still respond to Omicron and will be strengthened by enhanced immunity. Therefore, vigorously promoting enhanced immunity for high-risk groups will play an important role in controlling the severity and mortality caused by Omicron.

Are there any related sequelae of infection with the Omicron variant?

Faced with soaring body temperature, "Baojuan"'s hoarseness, and flocks of "sheep", people can't help but worry about whether they will suffer from "new crown sequelae."

So what is "post-COVID sequelae"?

The WHO calls those symptoms that appear three months after infection with the new coronavirus, last for at least two months , and cannot be explained by other diagnoses " post-COVID-19 symptoms ," or " COVID-19 sequelae ."

For sequelae associated with infection with the original strain and other VOCs, the most common were fatigue, pain or discomfort, shortness of breath, cognitive impairment, and mental health problems.

A recent study published in JAMA divides COVID-19 sequelae into three symptom groups:

①Persistent fatigue accompanied by body pain (muscle pain) or mood swings;

② Cognitive problems (forgetfulness or difficulty concentrating, i.e. brain fog);

③Persistent respiratory problems (mainly shortness of breath and persistent cough).

The study's analysis of follow-up data from 1.2 million confirmed COVID-19 patients showed that only 6.2% still had at least one sequelae symptom three months after symptomatic infection.

In addition, the severity of infection is closely related to the occurrence of sequelae. The proportions of ICU patients, hospitalized patients, and non-hospitalized patients who still had sequelae three months after infection were 43.1%, 27.5%, and 5.7%, respectively.

As for the sequelae associated with Omicron infection, since it requires a long period of observation, there is currently only partial evidence that the incidence of sequelae associated with Omicron infection is lower than that of Delta. For example, a study recently published by Lancet compared 56,003 cases of Omicron infection during the epidemic and 41,361 cases of Delta infection during the epidemic and found that 10.8% of Delta infections developed sequelae, while the proportion of Omicron infection sequelae was 4.5%. Compared with Delta, the incidence of sequelae in Omicron was reduced by 24% to 50%.

Therefore, existing research only suggests that the occurrence of COVID-19 sequelae is highly correlated with the severity of the infection, and asymptomatic infected people will hardly suffer from sequelae. The results of long-term observations still need to be further studied.

Could it be influenza if it is not positive?

How do you view Omicron infection and seasonal influenza?

Perhaps you have also experienced high fever, cough, sore throat, and fatigue , but the results of repeated self-tests for antigens are always " negative ", and you can't help but worry: Could it be seasonal flu ?

Indeed, not only is Omicron's extremely strong transmission ability and significantly lower mortality rate becoming more and more similar to the seasonal influenza that the public is familiar with, but Omicron's invasion site has also shifted from the lower respiratory tract to the upper respiratory tract compared to previous variants, so its infection-related symptoms are also similar to those of the influenza virus.

Most young and middle-aged patients who have been vaccinated and have no underlying diseases will usually experience symptoms of dry throat and fatigue on the first day after being infected with the Omicron variant; they will start to have a fever and worsen sore throat symptoms on the second day; high fever symptoms will appear on the third day and sore throat will worsen, and then the symptoms will be very similar to those of influenza, and usually the symptoms will be significantly relieved on the fifth or sixth day .

In terms of disease severity, epidemiological data from seasonal influenza were used to compare with the COVID-19 pandemic as early as the early stages of the outbreak. Studies have shown that the mortality rate caused by infection with the original strain was higher than that of influenza virus in the early stages of the outbreak. During the Omicron epidemic, researchers used mathematical model analysis to show that the mortality rate of Omicron was lower than that of seasonal influenza and the 2009 H1N1 influenza.

In fact, since influenza is not screened on a large scale like COVID-19, it is very difficult to scientifically and systematically compare the mortality rates of the two. However, combined with the epidemic data of various countries, a rough comparison shows that the severity and mortality rates related to Omicron infection have dropped to a level similar to that of seasonal influenza, but its transmission ability far exceeds that of seasonal influenza. The number of deaths caused by Omicron infection (especially for the elderly) cannot be underestimated.

More importantly, with the relaxation of epidemic prevention policies, we will face a dual epidemic of Omicron and influenza in the future, which will be a major threat to high-risk groups.

Therefore, in the face of the current epidemic of Omicron, which has a low mortality rate and high infection rate, no matter whether you have tested positive or not, please do not worry too much, let alone be "fearful of positive" or "illusion of positive". The key is to deal with it correctly and properly and alleviate the current symptoms. Especially for special groups such as the elderly and the weak, they should be more vigilant, actively get vaccinated, and intervene reasonably to avoid the dual epidemic of Omicron and influenza .

Last words

The COVID-19 pandemic is about to enter its fourth year. From the original strain to the fifth generation VOC that has swept the world, Omicron has undergone significant changes in its genome and biological characteristics. Its strong transmission ability is accompanied by a decrease in the pathogenicity of the virus itself. Combined with the immune barrier of the population established by previous infections and vaccines, compared with other variants, Omicron has shown strong transmission ability, low severity and mortality, opening a new starting point for the COVID-19 pandemic. Human society's understanding and response to the COVID-19 pandemic should also reach a new stage.

Omicron's strong ability to spread and escape immunity makes previous infection and vaccines have very limited ability to prevent repeated infection. For China, as Omicron continues to break through the barriers of epidemic prevention and the loss of epidemic prevention resources continues to increase, whether it can coexist with the virus is no longer a question, but when to coexist with the virus at the lowest cost.

Unlike other countries in the world that have "fallen flat" one after another, China has a special national condition. In the early stage of the epidemic, China's epidemic prevention policy protected people's livelihood and economy to a great extent, but to a certain extent, it also led to the lack of mixed immune barriers established by previous infections and vaccines. Of course, this was also achieved at a great cost by other countries.

Vaccines provide limited protection against Omicron. Currently, the proportion of high-risk populations in China who have received enhanced immunization is low. Although the mortality rate caused by Omicron infection has been significantly reduced, Omicron's strong ability to spread means that we must not underestimate the death toll and the medical run that may occur after coexistence. Omicron is also constantly evolving. No one knows the future epidemic trends and the impact of dominant variants on humans and society. How China adjusts its epidemic prevention policies to achieve a "soft landing" is a test.

At present, the most important thing is to increase the booster vaccination rate for high-risk groups, mainly the elderly. Booster immunization plays an important role in preventing severe illness and death caused by Omicron infection. An article estimates through modeling that if all people over 60 years old complete booster vaccination, China's mortality rate will be reduced by 61%. However, the current booster vaccination rate for people over 60 years old in mainland China is 69%, and the booster vaccination rate for people over 80 years old is only 40%. Improving the booster vaccination level of high-risk groups is the primary condition for gradual relaxation.

Secondly, we encourage heterologous vaccination of different types of vaccines and the fourth dose of vaccination. In addition, we must be prepared for possible medical runs, increase publicity and popularization efforts to eliminate public panic and reduce blind medical treatment and run on medical resources. At the same time, hospitals should also strengthen tiered diagnosis and treatment to ensure that severe and critical illnesses are treated in a timely manner, and use small molecule antiviral drugs in the early stages of high-risk patients to reduce the possibility of disease progression.

In summary, the 2022 Omicron pandemic has opened a new starting point for the COVID-19 pandemic, and my country's epidemic prevention and control is facing new situations and new tasks. On the basis of vigorously promoting the strengthening of immunity for high-risk groups, we will gradually relax epidemic prevention and control, prevent medical rush, protect high-risk groups, and gradually adjust the epidemic prevention strategy to shift the focus of epidemic prevention to the prevention and control of severe illness and death, while insisting on epidemiological monitoring to prepare for the possible emergence of new variants.

▌The popular science theme of this article comes from the review article "New Challenges of the COVID-19 Pandemic: Characteristics of Omicron Variants and the New Stage of Scientific Epidemic Prevention" in the "Journal of Peking Union Medical College"

Original author: Li Yi, Xu Yingchun

Editor: Liu Yang and Zhao Na

Proofread by Li Na, Li Yule, and Dong Zhe

Producer: Wu Wenming

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