SINGAPORE - The Sars-CoV-2 virus that sparked the Covid-19 pandemic has undergone more than 6,600 unique spike protein mutations, said Dr Sebastian Maurer-Stroh, executive director of the Bioinformatics Institute at the Agency for Science, Technology and Research (A*Star).
Viruses mutate whenever there is a "mistake" in the replication process. This could result from an addition, a deletion or a change to its genetic code.
If that mistake increases its survival prospects, more copies of that "wrong" replication will survive, and sometimes overwhelm the original version.
For example, the D614G mutation which started to rise sharply in February last year is now found in all samples of the virus, no matter which variant they are.
Because this variant became so pervasive, it was given a clade name - or family group - of its own, and is designated as G clade.
The World Health Organisation (WHO) says that while the G clade has increased infectivity and transmission, the illness it causes is not more severe, nor does it affect diagnostics, treatment or vaccines.
This G clade and its sub clades - which include GRY, a clade named for the UK variant B117 in July last year - have accounted for practically all Covid-19 infections since the middle of last year, totally displacing the original virus that emerged in Wuhan.
So if there are so many mutations of the virus, why does the World Health Organisation list only three of "concern" so far, and a handful that are of "interest", and practically ignore the rest?
To qualify as a variant of concern (VOC), the mutated virus has to show evidence in fulfilling at least one of these criteria: that it transmits more easily, causes more severe illness, significantly reduces neutralisation by antibodies, or reduces the effectiveness of treatment, vaccines or diagnosis.
Dr Maurer-Stroh explained that not all mutations make a difference to the disease in these ways. Hence, these mutations do not make waves.
Variants usually comprise a set of five to 15 mutations that, together, give them some added advantage.
Dr Maurer-Stroh said the terms "double mutant" or "triple mutant" variants used to describe the virus strains rampaging in India are therefore a misnomer, but broadly refer to the more significant mutations found in those variants.
Fortunately, there are only three VOCs right now.
However, there are several variants of interest (VOI) which appear to exhibit some of the characteristics of a VOC, but without sufficient evidence for the moment. That may change.
They include the two variants first detected in India that are causing the huge surge in cases over the past month.
In spite of the spiralling number of cases and deaths in India - 22 million cases and more than 235,000 deaths - the WHO has not classified them as VOCs as there is still uncertainty over how much of the spread of Covid-19 there is caused by the variants and how much is due to other factors such as poor safety measures and insufficient hospital capacity.
There have been more than 6,600 unique mutations to the coronavirus' spike protein since it emerged in December 2019, said Dr Maurer-Stroh, who is involved in collecting and analysing changes to the viral genome under the Gisaid data-sharing platform, which has enabled global sharing of more than 1.5 million virus sequences.
This works out to one unique mutation every two hours, day or night.
Are the vaccines available today of any use against these variants?
Definitely, said Professor Ooi Eng Eong of the Duke-NUS Medical School, who is himself involved in developing an mRNA vaccine. He said: "Studies among vaccinated individuals have found that the mRNA vaccines are also capable of preventing infection from the various variants of concern.
"At least four reports have shown that the rate of breakthrough symptomatic variant Sars-CoV-2 infection has been below 1 per cent among vaccinated individuals."
Antibodies produced by vaccines recognise part of the spikes on the virus. The concern is if the part that the vaccine recognises is changed, would it still be able to protect people who have been vaccinated?
Prof Ooi explained that vaccines do not just produce antibodies, but also "activate a suite of immune responses" in the body, including the production of T cells that kill both the virus and infected cells. These would not be affected by changes in the spike protein.
However, Associate Professor Hsu Liyang, an infectious diseases expert at the National University of Singapore's Saw Swee Hock School of Public Health, added a word of caution about assuming that current vaccines will remain as protective.
What applies today may not always be the case, he said. "We don't expect the virus to stay still. There will be more variants thrown up."