What is behind the rapid disappearance of the delta variant of Covid-19 in Japan? Maybe it’s self destruct

(ORDO NEWS) — Why did the fifth and largest wave of the coronavirus pandemic in Japan, caused by the super-infectious delta version, end abruptly after a seemingly steady rise in new infections? And how does Japan differ from other developed countries, which are now seeing a new surge in new cases?

According to one group of researchers, the unexpected answer may be that the delta variant took care of itself by performing an act of “self-destruction”.

Three months after the delta variant led to a record daily number of cases nationwide of nearly 26,000, the number of new COVID-19 cases in Japan has dropped sharply, falling below 200 in recent weeks. The decline underscores the fact that No fatalities were reported on November 7, the first time in 15 months.

Many scientists point to various possibilities, among which one of the highest vaccination rates in developed countries: as of Wednesday, 75.7% of residents were fully vaccinated. Other potential factors are social distancing measures and the wearing of masks, which are now deeply ingrained in Japanese society.

But the main reason may be related to the genetic changes that the coronavirus undergoes during the reproduction process, at a rate of about two mutations per month. According to a potentially revolutionary theory proposed by Ituro Inoue, a professor at the National Institute of Genetics, the delta variant in Japan has accumulated too many mutations in the non-structural protein nsp14, which corrects the virus’s errors. As a result, the virus did not have time to correct errors, which ultimately led to “self-destruction”.

Research has shown that more people in Asia have a protective enzyme called APOBEC3A that attacks RNA viruses, including the SARS-CoV-2 virus that causes COVID-19, compared to people in Europe and Africa.

Therefore, researchers from the National Institute of Genetics and Niigata University set out to find out how the APOBEC3A protein affects the nsp14 protein and whether it can suppress the activity of the coronavirus. The team analyzed data on the genetic diversity of alpha and delta variants obtained from infected clinical samples in Japan from June to October.

They then visualized the connections between the DNA sequences of the SARS-CoV-2 virus to show genetic diversity in a diagram called a haplotype network. In general, the larger the network, the more positive cases it presents.

The alpha variant network, which was the main driving force behind the fourth wave in Japan from March to June, consisted of five main groups with many mutations branching in different directions, which confirms the high level of genetic diversity. The researchers also believed that the delta variant, which, according to the US Centers for Disease Control and Prevention, is more than twice as infectious as previous variants and could cause more severe disease in unvaccinated people, would have much more striking genetic diversity.

Surprisingly, they found the opposite. The haplotype network consisted of only two main groups, and mutations seemed to suddenly stop in the middle of the evolutionary development process. When the researchers moved on to study the error-correcting enzyme nsp14 of the virus, they found that the vast majority of nsp14 samples in Japan had undergone many genetic changes at mutation sites called A394V.

” We were literally shocked by the results of the study ,” Inoue said in an interview with The Japan Times.

“The delta variant in Japan was highly transmissible and did not allow for other variants. But as mutations accumulated, we believe that eventually the virus became defective and could not make copies of itself.” Given that the number of cases of the disease did not increase, we believe that at some point during these mutations, he headed straight for his natural extinction . ”

Inoue’s theory, while innovative, confirms the mysterious disappearance of the spread of the delta variant in Japan . At that time most of the rest of the world with the same high level of vaccination, including South Korea and some Western countries, suffers from a record wave of new infections, Japan seems to be an unusual case because COVID-19 disease cases remain restrained, despite the trains fill and restaurants since the end of the last state of emergency.

“If the virus were alive and well, the incidence would surely be more frequent, since camouflage and vaccinations do not prevent breakthrough infections in some cases,” Inoue said.

According to Takeshi Urano, a professor at Shimane University School of Medicine who was not involved in Inoue’s study, the unexpected spike in new cases following the summer surge has been the subject of heated debate among many experts, including those who have not done coronavirus research.

“Nsp14 works with other proteins in the virus and has a critical function of protecting the virus’s RNA from decay,” he said, when asked about Inoue’s findings. “Research has shown that a virus with damaged nsp14 has a significantly reduced ability to replicate, so this could be one factor in the rapid decline in new cases.” nsp14 is a virus derivative, and a chemical to inhibit this protein could be a promising drug under development. ”

Japan appears to be an anomaly, as by the end of August, the delta option has largely supplanted the alpha and other options. On the other hand, other countries, including India and Indonesia, which are particularly hard hit by the delta variant, report mixed alpha and delta strains among those affected.

Inoue says that a similar natural disappearance of the coronavirus could be observed abroad, adding that it will be difficult to detect this, since no other country seems to have accumulated as many mutations in the nsp14 virus as in Japan, although similar mutations in the A394V region have been found in at least 24 countries.

But Inoue’s theory may also help explain why the outbreak of severe acute respiratory syndrome (SARS) ended abruptly in 2003. An in vitro experiment, in which the researchers caused mutations in nsp14 in the virus that causes SARS, concluded that the virus ultimately could not replicate as mutations accumulated.

“No genomic data exists, so this is just a hypothesis, but since it disappeared, it will never see the light of day,” he said.

What are the chances that we will see a similar natural disappearance of the COVID-19 virus that causes SARS-CoV-2 abroad?

“The chances are not zero, but so far it seems too optimistic, since we have not been able to obtain any such evidence, although we have studied various data from other countries ,” he said.

After peaking in mid-August, daily COVID-19 cases in Japan continued to decline, falling below 5,000 by mid-September and below 200 by the end of October. According to Inoue, the country has had one of the lowest levels for some time infection among all developed countries, but it is not immune to the next wave of the pandemic.
“Obviously there is a threat,” he said.

“We were fine, because there was a delta option. Other options penetrated gradually, but the Japanese delta held them back. But since nothing is holding them back now, there is an opportunity for new ones to penetrate, since vaccines alone cannot solve the problem . I think that quarantine measures to control immigration are very important, because we never know what gets into the country from other countries. ”

Some people may wonder if the self-destruction of the delta variant in Japan is caused by something special in the genetic makeup of the Japanese, but Inoue disagrees.

“I don’t think so,” he said. “People in East Asia like Koreans are ethnically the same as Japanese. But I don’t know why this observation was made in Japan.”

Inoue said a team of researchers from the National Institute of Genetics and Niigata University plans to compile a study of their findings by the end of November.

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