Coronavirus: Fact-check - did mutations or ivermectin help stamp out Delta in Japan?

Just how Japan managed to crush its outbreak of the Delta variant has sparked a range of new theories, but one expert says it's down to nothing more exciting than boring old vaccines and public health measures. 

Three months ago the Asian nation of 126 million people was recording more than 24,000 cases and close to 90 deaths a day, experiencing a massive wave of infection in the wake of the Olympic Games. 

But in the space of three weeks the daily case numbers dropped more than 70 percent, by October they were below 2000 a day and right now - in late November - their rolling average is lower than New Zealand's. 

A popular UK health YouTuber John Campbell dubbed it the "Miracle in Japan", citing two potential reasons. The first is that the virus mutated itself into a state where it couldn't reproduce effectively - a new theory put forward by a top Japanese genetic researcher earlier this week; the second, that old staple of conspiracy theorists and fake news peddlers - the anti-parasitic medicine ivermectin, which is has yet to be shown to be effective against COVID-19 in any reputable medical trial

Misinformation websites also picked up on the claims 

Both theories have significant problems however. 

Ivermectin

In late October, a white supremacist radio broadcaster in the US who's served prison time falsely claimed Japan's success came after the nation cancelled its vaccine rollout and started using ivermectin instead.

The claim was picked up on social media and spread like, well, Delta - many noting the decline in cases began two weeks after a top Japanese doctor recommended the use of ivermectin.

Problem is, it's not true. Japan's vaccine rollout - after a sluggish start - was ticking along quite nicely in August, about 1 percent of the country getting a dose each day according to Japanese health authorities. It's trailed off a bit since then, as vaccine rollouts do once most people have been jabbed, reaching an impressive 79 percent of the total population as of late November. 

There was a temporary halt on the use of the Moderna vaccine after a contamination scare, but it's still being used.

Japan also never approved the use of ivermectin for use against COVID-19. The doctor who suggested in August it might be an option -  if further research found it to be effective - was chair of the Tokyo Medical Association (TMA), which is not a governmental agency and has no authority to make such a decree. Nor is ivermectin listed as an approved treatment by the Japanese government

Meaghan Kall, head of COVID-19 epidemiology at the UK Health Security Agency, said the entirety of the evidence that ivermectin is behind Japan's success is a coincidence - that the decline began two weeks after the TMA doctor's suggestion. 

"The video's primary argument is a classic case of correlation ≠ causation," she tweeted of Dr Campbell's claims, saying there was no evidence ivermectin was even being prescribed in large amounts for off-label use, or by people self-treating themselves with product - usually intended for livestock - off the internet. 

"There is none. Zip zero nada," she said. "It appears this is based on anecdata on social media driving wildly damaging misinformation."

Studies which have found ivermectin works against COVID-19 have routinely been retracted or widely criticised as flawed or outright fraudulent. Even companies that manufacture it - and stand to profit from sales - have warned people not to use it for treating or preventing COVID-19.

Mutation

Earlier this week Ituro Inoue, a professor at the National Institute of Genetics, floated the idea that the Delta virus spreading in Japan accumulated too many mutations and rendered itself unable to make copies.

"We were literally shocked to see the findings," he 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."

There was little genetic variation in samples of the virus collected by his team, and combined with a gene common in Asian people that has strong antiviral properties, Dr Inoue said this might have been behind the outbreak's collapse. 

Dr Campbell picked up on this, suggesting thousands of years without much "genetic interbreeding" has resulted in mutations in their DNA which has given them a unique ability to fight off the virus. Dr Inoue preempted this kind of talk by pointing out South Koreans are genetically similar to Japanese but haven't had the same success at quelling their recent Delta outbreak. 

But there's an obvious problem the theory has to overcome - not every copy of a virus mutates in the same way at the same time - like it does popular game Plague Inc, for example - making it unlikely a widespread outbreak can be ended this way.

"This has never happened to an RNA virus in the wild, only proven in controlled laboratory conditions," wrote Dr Kall.

"This can only naturally happen where transmission [is] low enough to allow for a transmission bottleneck AND no healthy virus is circulating for recombination."

Recombination is when two viruses infect a host cell at the same time, and the resulting 'copies' inherit genes from both - viruses with faulty genes would have theirs overridden by working copies. Without recombination, outbreaks are susceptible to a phenomenon called 'Muller's ratchet' - an accumulation of disadvantageous mutations, as described by Dr Inoue.

"In a setting of active transmission the mutations would be of such harm to the virus that it has no evolutionary advantage and the healthier viruses would win out & continue to evolve," said Dr Kall. "Further, even if this phenomenon was occurring in a captive population, then even one incursion or recombination with a healthy virus could scupper the whole thing."

Dr Kall said now that case numbers are low, it's possible Muller's ratchet could be keeping the outbreak in check - but unless the virus is eliminated from Japan completely, it's only a temporary reprieve.

"Once travel restrictions are lifted & international movement is resumed, and as long as COVID-19 is in an endemic or epidemic phase anywhere, the conditions do not allow the virus to mutate into extinction in this way - naturally at least."

The likely real cause

Dr Kall notes there was a massive influx into Japan in July for the Olympics, and "substantial increases in mobility". Cases peaked soon afterwards. 

Japan's vaccine rollout peaked in early August, and maintained a good rate through to October - almost doubling coverage in just two months. The jabs take a few weeks to really kick in, so this lines up with the fall in cases too. 

And Dr Kall notes Japan was in a state of emergency from April until October, when restrictions were lifted as case numbers began plummeting - so the outbreak likely sparked by the Olympic Games was snuffed out before it could spiral completely out of control. 

"The combination of these events and prevention measures make for a much more compelling argument," she wrote.