A (Possible) Solution to COVID-19
Like nearly everyone on the planet I am worried about COVID-19. SARS-CoV-2 (the virus that causes COVID-19) appears to be killing between 1% to 3.5% of the people we know it infects (i.e the case fatality rate) and has a R0 (i.e. how many new people each person infected goes on to infect) of between 2.5 to 3.9 or even higher.
Newer reliable serology data, such as the studies done in Switzerland and China (i.e. not Santa Clara or Los Angeles), suggests the true infection fatality rate (IFR) is around 1%. Left to run wild, this virus will kill tens of millions of people worldwide.
Many governments of the world have implemented strict population isolation protocols to try and limit the spread of the virus, but the economic cost of this is extremely high. A vaccine for COVID-19 is 12 to 18 months away (at best).
We are stuck in a diabolic situation where the only way to prevent the economy sliding into a slump deeper than the Great Depression is to consign many tens of millions of people to an early grave. Is there a way out?
SARS-Cov-2 Viral Diversity
SARS-CoV-2 like all viruses mutates (changes) overtime. Many of these genetic changes are small (single nucleotides) that are not important to the replications or transmission of the virus from person to person, but they can be used to identify the origin of the virus. DeCODE genetics for example has been testing Icelanders for COVID-19 and genome sequencing the SARS-CoV-2 strains isolated. They (and others) have found two very important pieces of information:
- More than 50% of the people infected with SARS-CoV-2 are asymptomatic or have only a mild case (i.e. they have no serious illness).
- They can identify the geographical origin of the strains by the genetic differences (mutations) between the different strains.
Furthermore, researchers in China have identified a mutant strain of SARS-CoV-2 which appears to be less pathogenic than most strains infecting people. The strain (ZJ01) had single nucleotide mutations in a key functional gene that made it less able to spread through the body. A recent pre-print paper from Singapore has described a mutant strain of SARS-CoV-2 with a 382 nucleotide deletion that was found in a cluster of patients in one of their hospitals. An even more recent paper from China found 11 of strains of SARS-CoV-2 with variation in pathogenicity in cell culture.
This data suggests a simple and testable hypothesis – there are natural strains of SARS-CoV-2 in the world that have mutated to be non-pathogenic (asymptomatic or mild), but which are still infective and will provide immunity to the more pathogenic (deadly) strains.
If we can find one of these non-pathogenic viral strains out in the wild we could give it to everyone in the world and solve our diabolic problem. This non-pathogenic (attenuated) strain would act much like the live attenuated (oral) polio vaccine.
How do we find an attenuated SARS-CoV-2 strain?
This hypothesis is worthless if we have no way of finding any of these non-pathogenic SARS-CoV-2 viral strains. Luckily there is a quick and cheap way to find these strains if they exist – test asymptomatic/mild case swab samples for COVID-19 and then genome sequence the SARS-CoV-2 strain that has infected them with the aim of identifying a virus with mutation(s) in essential viral gene(s). This is what the Chinese researchers did to find their less pathogenic strains and how the Singaporean researchers found their deletion mutant strain.
This approach is cheap (a couple of hundreds of dollars per virus strain) and quick (a week or less). With little cost we could sequence a few thousand viral strains, or even tens of thousands of strains, from positive swab sample from asymptomatic and/or mild case until we find a virus strain with the right mutations to make it harmless and which could work like a vaccine to protect us from the dangerous strains. We would know from epidemiology that this strain can still reproduce in people and lead to immunity, but not make people seriously ill.
Update. I have written a step-by-step post on one way we might go about putting this proposal into action.
What viral mutations are we looking for in a good non-pathogenic viral strain?
We would ideally be looking for a virus strain with a large(ish) deletion in an essential viral gene like the strain found in Singapore (unfortunately this strain is too dangerous to use as it put people into hospital). This sort of deletion mutation is easy to spot in the SARS-CoV-2 genome data, and because the genetic information has been removed, it makes the virus unlikely to be able to mutate back into a dangerous strain. Ideally, the strain identified will have infected a large number of other people in the local area so we can know it is safe from the epidemiological data. This will be important for getting regulatory approval to use the strain.
Has this ever been done before?
Yes. The polio, measles, rubella, mumps, and chickenpox vaccines are all live attenuated viruses. Even something as dangerous as smallpox was controlled in the 18th century using a variation of this idea called Variolation. The idea was the doctor would deliberately infect you with a less harmful strain of smallpox (often at a low dose) to make you immune to the more deadly strains of smallpox. Of course, they didn’t know how this approach worked in the 18th century, but it was still very effective and millions of people were saved from dying from smallpox by it.
Some people have been calling using a low dose of the virus Variolation, this is not what we think Variolation was, but this is a complex topic. While such a low-dose approach of the dangerous strain might make the COVID-19 less dangerous to the person being deliberately infected, it doesn’t make the virus any less dangerous for those around you that you might infect later. Such an approach could also not be used on the vulnerable, leaving them exposed to the illness. There is no reason in principle that the low dose idea couldn’t be combined with the attenuated strain idea and it might even be a very good idea.
In regards Corona viruses, there was considerable work done on determining which regions of the SARS-CoV can be deleted to create an attenuated virus that provided protection from the wild type dangerous version. Jose Regla-Nava and colleagues identified that SARS strains with gene deletions in the E protein were attenuated and provided good protection from later infection with SARS-CoV. Furthermore, these researchers found the deletion strains were genetically stable when grown in cell culture. SARS-CoV-2 contains the same E protein and deletions in the E protein gene may provide the same attenuation.
What are the risks?
The major risk is a mutant virus we think is safe is not 100% safe. While we can use community spread of the identified strain to estimate how safe it will be (i.e. if it has infected 1000 people and none have got seriously ill then we should have a pretty good idea that it is safe), our knowledge will be incomplete. We can of course spend the next few years testing and trialling, but if we do this by the time any strain is shown to be 99.99% safe (not even the polio vaccine is 100% safe) we will have all got COVID-19 and the world’s economy will be a smoking ruin.
We have a choice of taking some risks now, or face the certainty of a much worse problem later. Time to accept some risk and do something now.