Three months after the delta variant spurred record daily nationwide caseloads of nearly 26,000, new COVID-19 infections in Japan have plummeted, dropping below 200 in recent weeks. Highlighting that drop was the fact that no deaths were reported on Nov. 7 — the first time that had happened in about 15 months.
Many scholars point to a variety of possibilities, which include one of the highest vaccination rates among advanced countries with 75.7% of residents fully vaccinated as of Wednesday. Other potential factors are the social distancing and mask-wearing measures that are now deeply embedded in Japanese society.
But the chief reason may be related to the genetic changes that the coronavirus undergoes during reproduction, at a pace of around 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 accumulated too many mutations to the virus’s error-correcting, non-structural protein called nsp14. As a result, the virus struggled to repair the errors in time, ultimately leading to “self-destruction.”
When the researchers went on to examine the virus’s error-correcting enzyme nsp14, they discovered that the vast majority of nsp14 specimens in Japan seemed to have undergone many genetic changes in mutation sites called A394V.
“We were literally shocked to see the findings,” Inoue told The Japan Times. “The delta variant in Japan was highly transmissible and keeping other variants out. But as the mutations piled up, we believe it eventually became a faulty virus and it was unable to make copies of itself. Considering that the cases haven’t been increasing, we think that at some point during such mutations it headed straight toward its natural extinction.”
Inoue’s theory, while innovative, would lend support to the mysterious disappearance of the delta variant’s spread in Japan. While much of the rest of the world with similarly high vaccination rates, including South Korea and some Western countries, are suffering from record waves of new infections, Japan appears to be a peculiar case in that COVID-19 cases have remained subdued despite trains and restaurants filling up following the end of the most recent state of emergency.
“If the virus were alive and well, cases for sure would increase as masking and vaccination do not prevent breakthrough infections in some cases,” Inoue said.
“Nsp14 works with other virus proteins and has a critical function to protect the virus RNA from breaking apart,” he said when asked about Inoue’s findings. “Studies have shown that a virus with a crippled nsp14 has a significantly reduced ability to replicate, so this can be one factor behind the rapid decline in new cases. The nsp14 is virus-derived, and the chemical agent to curb this protein could become a promising medicine, with development already underway.”
Japan seems to be an anomaly in that the delta variant was virtually shutting out alpha and other variants by late August. On the other hand, other countries — including India and Indonesia, both of which were hit particularly hard by the delta variant — have reported a mix of alpha and delta strains among cases.
A similar natural extinction of the coronavirus could possibly be observed overseas, Inoue says, adding that detecting that would be difficult as no other country seems to have accumulated as many mutations in the virus’s nsp14 as in Japan, though similar mutations at the A394V site have been discovered 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 led to findings that the virus eventually could not replicate itself as mutations piled up.