In my first post on a possible solution to COVID-19 I hypothesised that there would be gene deletion mutants to be found in the SARS-CoV-2 viral strains out in the world and that we would find them if we looked.
Unfortunately, when I posted there were very few full genome sequences in the public databases (under 1000) and many of these sequences were of low quality and contained gaps due to poor sequencing coverage. These gaps look like gene deletions when you try to do bioinformatic analysis.
Since then the COVID-19 Genomics UK Consortium (COG-UK) has released 10,567 complete SARS-CoV-2 genome sequences. Bioinformatic analysis of this data has revealed 69 of these genome sequences contained gene deletions. The full list can be found here, but here is a partial list.
Partial list of the gene deletions found in the COG-UK SARS-CoV-2 genome sequence data
The really interesting deletion mutations are those in the non-structural accessory genes. These are the genes that are likely to play an important role in pathogenicity and it would be expected that some of these mutations may make the virus less dangerous (attenuated).
The next step (beyond obtaining more sequences from locations other than the UK) is to go and visit the people who were infected with each of the different deletion strains and investigate what was their clinical outcome. If the patient only had a mild case of COVID-19 then we have a potential attenuated strain and we need to look for more cases caused by this mutant strain in the local area (including in the hospitals).
If we find that everyone who was infected with a particular deletion strain only had a mild case of COVID-19, then we have our candidate attenuated strain which could be used to accelerate vaccine development in a challenge trial. Finding such an attenuated strain should allow us to shave many months off the development of an effective vaccine that will protect us from this terrible pandemic. The value of this in both lives and dollars saved is immense.
Really glad that there might be a path to vaccine using “less dangerous” strain. Would you be able to correlate the strain with geography and mortality? Would there be some correlation?
Jean-Philippe there could be, but nobody has yet looked. The only way to answer these questions is to get out and look.
How do you know that a deletion strain infected enough individuals to allow a meaningful correlation between infection and symptoms. If only a few patients infected with the same deletion strain were available, then who is to say that their mild symptoms were due to the deletion rather than to a strong immune system?
You don’t for any particular deletion strain pickup in the initial screening, but part of the criteria for choosing a natural attenuated strain is it has to have infected enough people to allow you determine that it is attenuated via epidemiology. My expectation is some deletions strains will be attenuated, but they just won’t have infect many people yet, but we just put them aside and look for those that have.
That still sounds like a long, tedious process. How much effort is required to find such strains in populations? How much time do you save compared to the traditional vaccine development approach?
No it is actually a quick and easy process to find strains. Have a look at my post on how this approach would be put into practice.
As for how much time it would save at least 3 months and maybe upto 12 months.