A new strain of Omicron has been detected in India and Singapore. Can we still take off our masks?

The immune barrier of the population has been strengthened, and most people do not need to be afraid of the current new strains, but everyone should take appropriate epidemic prevention measures based on their actual situation.

Written by Zhou Yebin

1

A new member of the Omicron family?

Recently, the COVID-19 outbreak has resurfaced in Singapore, India and other places[1]. Monitoring agencies have discovered a new strain of the novel coronavirus spreading in these places. The name of this strain is quite strange: Arcturus, which is a star located in the constellation Bootes and the third brightest star in the sky.

The Arcturus strain has an obscure real name: XBB.1.16. The World Health Organization (WHO) has stated that it is concerned about this new strain of the virus. [2]

We already know that the new coronavirus, like all viruses, will continue to accumulate various mutations during the process of transmission. Over time, the virus may change in its ability to spread, pathogenicity, and immune escape characteristics. Therefore, it is very important to track the variants of the virus and give them names to distinguish them. The scientific community has adopted the Pangolin nomenclature to name the variants of the new coronavirus, which is based on the genome sequence of the virus and is named according to the evolutionary relationship between different variants. [3]

For example, the first alpha variant that had a significant impact on the epidemic was named B.1.1.7 by Pangolin, which means it is the seventh named branch under the B.1.1 virus strain, and B.1.1 is a sub-branch of the B.1 virus strain. However, as the new coronavirus continues to spread, the branches of the virus strains continue to be inherited. If the naming method is only to add decimal points and numbers, then the names of the popular virus strains will be too long to be used in daily communication, and it is also easy to make mistakes.

Therefore, when the Pangolin name reaches 4 decimal points, the previous letters will be changed so that the virus still has a relatively concise name. For example, the subclade of Omicron becomes BA.1, BA.2, BA.5, etc. From the end of 2022 to the beginning of 2023, during the first wave of Omicron epidemic in China, there was a major virus strain called BF.7, which is actually the BA.5 strain, which is a simplified Pangolin strain name of BA.5.2.1.7.

However, in addition to accumulating mutations through generations similar to "reproduction of offspring" to form new virus strains, the new coronavirus sometimes also undergoes recombination of different virus strains, thus producing new variants. In the Pangolin system, the initials X are specifically used to describe variants formed by such recombination, and the name XBB.1.16 also represents that it was originally derived from the recombination of two virus strains.

Referring to the principles mentioned above, Arcturus XBB.1.16 is the sixteenth independently named sub-lineage virus strain of the XBB.1 substrain, and XBB.1 is a recombination of the two virus strains BA.2.10.1 and BA.2.75 [4] . Since the first XBB case was detected in late September 2022, Singapore has formed a round of epidemics mainly caused by XBB and XBB.1 in October and November [4] . At the beginning of this year, XBB.1.5 became the most mainstream virus strain in the United States, and after March, it accounted for more than 80% of the new crown infection cases in the United States [5]. Therefore, Arcturus XBB.1.16 is not the first XBB strain to attract human attention.

Pangolin naming can help us determine the evolutionary relationship between different virus strains, but it is obscure and difficult to understand for the public. For this reason, the World Health Organization named some of the more influential virus strains with Greek letters, such as Alpha, Delta, Omicron, etc. However, this system became very embarrassing after the emergence of Omicron, because there are too many branches of Omicron, and none of them has a great impact alone and needs to be named separately, but putting them all together ignores the situation where different substrains have different immune escape characteristics and cause repeated epidemics.

Therefore, nicknames have become names that many media outlets are happy to use. For example, XBB.1.5 is called Kraken, a sea monster in Norse mythology, and Arcturus is also the nickname of XBB.1.16. With these strange nicknames from mythology or constellations, newly emerging virus strains can easily attract widespread attention. But you must know that the nickname itself has nothing to do with the pathogenicity, transmission ability, and immune escape of the virus strain, nor does it reflect the actual number of accumulated mutations or how different it is from previous virus strains. Therefore, we don't have to panic when we see a scary or strange nickname for a virus strain.

Now we need to note that both Kraken and Arcturus are still substrains of Omicron, and are similar to other Omicron substrains in many characteristics.

2

XBB.1.16 is not a big change

Although the nickname of Arcturus makes XBB.1.16 look extremely special, this mutant strain does not have any earth-shaking changes compared to other Omicron substrains that have been popular recently.

As a branch of XBB, XBB.1.16 is very similar to the current mainstream virus strain XBB.1.5 in the United States, and is not much different from the XBB that first attracted everyone's attention in Singapore. The biggest feature of the Omicron virus strain is that there are a large number of mutations in the spike protein (S protein), which leads to serious immune escape. The various substrains under Omicron have also formed extremely high diversity in the mutation of the S protein, and often a few amino acid changes can be used to obtain immune escape from the mainstream Omicron substrains in the past. Therefore, for any newly emerging Omicron substrain, we will pay close attention to whether it has new mutations in the S protein.

Analyzing the amino acid sequences of the S proteins of the three virus strains XBB, XBB.1.5, and XBB.1.16, we found that XBB.1.16 had a new mutation, E180V. Unlike the T478K mutation at amino acid position 478 of the first two strains, XBB.1.6 had a T478R mutation. At amino acid position 486, XBB.1.16 had the same F486P mutation as XBB.1.5, which was different from the F486S mutation of XBB[6].

Figure 1. Comparison of amino acid mutations in the S protein of three XBB virus strains [6]

The full-length S protein has thousands of amino acids, and even a single ACE2 receptor binding domain has more than 200 amino acids [7]. In terms of the number of mutations, XBB.1.16 is very different from the known XBB virus strains. It should be noted that when Omicron emerged, it relied on the fact that the S protein had as many as 32 amino acid mutations compared to the original strain, which allowed it to escape the immune system and cause a global epidemic.

Of course, if only a few amino acid mutations occur at some key positions, it may also cause the virus strain to undergo major changes in immune escape, cell invasion, and other aspects. However, over the past three years, scientists have accumulated a large amount of research and can better judge the impact of the new coronavirus mutation. Researchers have found that although there are many branches of Omicron today, quite a few branches have actually undergone convergent evolution in order to break through the common immune barrier of the population. That is, similar mutations have appeared on the S protein [8]. The XBB strain is no exception. Although it originated from the recombination of two virus strains and is not a close relative of BF.7, BQ.1 and other direct descendants of BA.5, it shares many mutation locations and even specific mutations on the S protein.

Figure 2. XBB and other recombinant SARS-CoV-2 variants have the same S protein mutations as other Omicron substrains, indicating convergent evolution[8]

Even when it comes to the competitive advantages that a specific mutation can bring, scientists can quickly give answers. For example, XBB has only become the mainstream virus strain in a few regions such as Singapore, with limited "spillover", while XBB.1.5 has "stood out" in the United States and defeated other strains such as BQ.1 and XBB. What is the reason behind this? It turns out that the F486S mutation of XBB is not conducive to the virus binding to the ACE2 receptor, while the F486P mutation of XBB.1.5 (the same as XBB.1.16) reverses this disadvantage, making the virus no longer weaker than other virus strains in utilizing the ACE2 receptor, that is, it has a transmission advantage, so XBB.1.5 can win in the competition among multiple virus strains [9]. Scientists discovered this reason when XBB.1.5 just entered its rising period in the United States.

The World Health Organization has also pointed out that the "T478R" mutation on XBB.1.16 is different from the mutations of the main XBB branch in the past. In the laboratory, it has been shown to increase the transmissibility and pathogenicity of the virus, so it is listed as a "strain of concern" [10] . At present, the media has widely reported that the number of cases in India and Singapore has increased. However, we should note that the number of cases in these two countries was extremely low before, and the number of cases after the surge is still lower than the previous peak of the epidemic, and there has been no significant fluctuation in severe cases and deaths.

3

Will the new variant bring us back to the peak of the epidemic?

Seeing terms such as "Kraken" and "Arcturus" appear frequently in media reports, it is inevitable to worry that the new mutant strain will bring us back to the peak of the epidemic.

This kind of vigilance is not an overreaction. After all, over the past three years, the emergence of new mutant strains has determined most of the fluctuations in the epidemic. When the epidemic caused by the original strain of the new coronavirus eased slightly, the Alpha, Beta, Gamma and other virus strains that appeared at the end of 2020 caused a more serious epidemic around the world. By the summer of 2021, just when everyone was full of hope for the new crown vaccine, the emergence of the Delta strain caused the epidemic to rebound rapidly. At the end of 2021, the Omicron strain brought an unprecedented peak of global infection.

However, we should note that after the emergence of the Omicron strain, with the improvement of the population's immune base brought about by global vaccination and natural infection, the current COVID-19 epidemic is very different from the past.

We can refer to the changes in infection cases in Singapore[11]:

Figure 3. Changes in new infections during periods when different virus strains dominated in Singapore [11]

When Singapore encountered the first wave of Omicron, BA.1/2 caused a large number of infections in a short period of time due to its strong immune escape and transmission speed. However, since then, although substrains such as BA.5 and XBB have made further progress in immune escape and their transmission speed is no less than BA.1/2, the severity of the epidemics they caused has been declining. This is because the immune foundation formed by vaccination and past infections has limited the impact of subsequent Omicron mutants .

Of course, newly emerged Omicron substrains such as XBB.1.16 tend to have stronger immune escape capabilities, especially against past Omicron virus strains. However, this immune escape is not complete, so the newly emerged Omicron substrains are still limited by past immune foundations. As can be seen in the figure below, after Singapore experienced several rounds of epidemics, the number of deaths in each round declined significantly:

Figure 4. Changes in the number of new deaths in Singapore during periods when different virus strains dominated the country[11]

As time goes by, the immunity level of the population will decline, and new mutants may also impact the immune barriers brought by past vaccination and natural infection through stronger immune escape. However, even a mutant strain like Omicron, which has emerged out of nowhere and can be said to belong to a completely different serotype from the original virus strain, still does not completely escape immunity. Therefore, we can be a little more assured that the newly emerged virus strains, whether XBB.1.5 or XBB.1.16, may only cause a small rebound in infection cases in some places, and will not cause a large number of severe cases or deaths.

As for the online rumor that Arcturus can cause conjunctivitis, or pink eye, it is certain that XBB.1.16 and other XBB virus strains are very similar in genome, and from a biological point of view, it is impossible for them to suddenly cause new symptoms. It is rare for the new coronavirus to cause eye symptoms, but there are also reports of conjunctivitis in infected people in the past. The so-called special cause of conjunctivitis is probably based on a few cases, just like the previous online rumor that XBB causes diarrhea, which caused some antidiarrheal drugs to be out of stock.

Some people are also concerned that the vaccines used in China are different from those used in Singapore. Will this affect our immune system? According to a study by researchers in Shanghai, after two doses of inactivated vaccine, neutralizing antibodies against XBB, XBB.1.5 and other virus strains were still detected six months after a breakthrough infection with BA.2 [12].

Figure 5. Neutralizing antibodies against various novel Omicron substrains were still detectable in inactivated vaccine recipients 6 months after breakthrough infection with BA.2 [12]

Of course, for new virus strains with stronger immune escape, such as XBB, the neutralizing antibody titer has dropped significantly. However, the existence of neutralization reaction itself proves that these new virus strains have not completely escaped immune in humoral immunity. Coupled with the cellular immunity that is more resistant to "mutation", we can also speculate that even if China has a second wave of epidemics due to a new Omicron substrain, the severity will be less than or even far less than the first wave of epidemics.

In recent months, China has not failed to detect new variants such as XBB. According to the national COVID-19 infection status released by the CDC on April 16, a total of 15 cases of Arcturus XBB.1.16 have been detected in the country [13], but the domestic epidemic is still at a low level.

4

Do I need to continue wearing the mask or put it on again?

Masks have protected most Chinese people, and they are also the symbol of public health measures most closely associated with the COVID-19 pandemic. Now it is the end of April, and the temperature is rising. Everyone is looking forward to taking off their masks and breathing freely. Now that a new virus strain has emerged, can the masks still be taken off?

As mentioned above, the immune basis of the population is significantly different from that before the Omicron outbreak. Even if mutant strains such as XBB.1.16 trigger a second wave of the epidemic, it will not be as severe as the first wave. It is also due to the blessing of the immune basis that for most healthy young people, even if the new mutant strains can bring a higher risk of secondary infection, the risk of severe illness is still very low.

In this case, we need to consider the benefits and necessity of various protective measures. Large-scale mask orders can reduce the spread of the new crown, but now with the rising temperature, it is becoming more and more inconvenient to wear masks for a long time. When the harm of the epidemic decreases, it is more reasonable to return the choice of wearing masks as a protective measure to individuals. This is why we see that Singapore, Hong Kong and other places have made lifting mask orders as a policy when they are determined to get out of the new crown emergency after the new crown threat decreases.

Some news about Arcturus XBB.1.16 claimed that India had reinstated the mask mandate, but in reality, only a few states in India have temporarily reinstated the requirement to wear masks in public places. Moreover, after the tragic experience of Delta, the Indian Ministry of Health also ordered hospitals to conduct large-scale infection response drills last week[14]. These policies are more out of caution and do not mean that India has encountered a serious epidemic again.

However, when we say that most people have a "low risk of severe illness", it does not mean that the new coronavirus has become milder for everyone. High-risk groups such as the elderly and immunosuppressed people are likely to be in a situation where "once infected, it is very dangerous" for a long time. For them, protective measures such as masks may be necessary.

The three-year global COVID-19 pandemic has passed, but the virus has not left human society. Faced with the emergence of new virus strains, a more reasonable response is to actively track the evolution of virus strains, and promptly determine which new virus strains may become mainstream and what impact they will have. At the same time, we must also pay attention to changes in the immune level of the population, and when necessary, introduce booster shots and other means to maintain the immune basis of the population. Finally, differentiated responses should be made according to the risks of different populations. High-risk groups not only need specific vaccination and treatment drug use plans, but also need differentiated recommendations on physical epidemic prevention measures such as masks.

References

[1] https://www.coronaheadsup.com/science/variants/recombinants/xbb-1-16/singapore-big-jump-in-xbb-1-16-suddenly-outcompetes-xbb-1-9-1/

[2] https://www.cnn.com/2023/04/06/health/coronavirus-omicron-xbb/index.html

[3] https://www.pango.network/the-pango-nomenclature-system/statement-of-nomenclature-rules/

[4] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00390-2/fulltext

[5] https://covid.cdc.gov/covid-data-tracker/#variant-proportions

[6] https://outbreak.info/compare-lineages?pango=XBB.1.5&pango=XBB.1.16&pango=XBB&gene=S&gene=ORF1b&gene=ORF1a&threshold=75&dark=false

[7] https://www.nature.com/articles/s41423-020-0400-4

[8] https://www.nature.com/articles/s41586-022-05644-7

[9] https://www.sciencedirect.com/science/article/pii/S1473309923000105?via%3Dihub

[10] https://www.who.int/multi-media/details/who-press-conference-on-covid-19-and-other-global-health-issues-29-march-2023

[11] https://covid19.who.int/region/wpro/country/sg

[12] https://www.biorxiv.org/content/10.1101/2023.02.07.527406v2.full

[13] https://www.chinacdc.cn/jkzt/crb/zl/szkb_11803/jszl_13141/202304/t20230415_265355.html

[14] https://www.independent.co.uk/news/health/arcturus-new-covid-variant-india-uk-b2319005.html

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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