The first-ever comprehensive gene sequencing of the Sars-CoV-2 virus isolated from samples in Kerala might not have thrown up anything surprising but the results could still be disturbing.
The study was done by the Institute of Genomics and Integrative Biology under Council of Scientific and Industrial Research (CSIR) and Academy of Scientific and Innovative Research with the help of Kozhikode Medical College. RNA samples were isolated from nasopharyngeal/oropharyngeal swabs of patients treated at the Government Medical College.
"We sequenced a total of 200 samples from patients but were able to properly investigate 113 of them," said Dr Chandni Radhkrishnan, head of Emergency Medicine at Kozhikode Medical College, who led the study.
Darwin at work
The study results were not surprising because almost all the samples isolated at the Kozhikode Medical College fell under a virus sub-type or variant now considered the most dominant in the world: A2a clade (group). It is the sub-type that is calling the shots in Europe and America.
The probability of the 'fittest' global variant sweeping through Kerala, too, was high, and the results just confirmed the hypothesis. It can also be said that Kerala is unlucky given that five other less aggressive sub-types have been identified in the country. The study has also found that the virus had got introduced to Kerala from Maharashtra, Odisha and Karnataka.
The disturbing part is, the 'fittest' variant is also possibly the most destructive.
The A2a group of Sars-CoV-2 is said to be the 'fittest' because of a specific mutation in its spike (S) gene. In precise terms, at the 614th amino acid position of the spike protein on the virus.
The study on Kerala samples has found that they, too, have this mutation at the 614th amino acid position. At that position, one type of amino acid (aspartic acid - D614) is converted into another kind (glycine - G614). The mutation is, therefore, called D614G.
D614G, by causing this amino acid alteration, allows the spikes or spear-like projections on the surface of the virus to have perhaps the best possible grip on an enzyme found on the surface of lung cells through which Sars-CoV-2 breaks into the human body.
With the mutation, it looks as if the virus has found the exact code word for entry into humans. It is not as if other sub-types cannot enter the human body. It is just that their break-in will not be as smooth as that of the virus type in the A2a clade.
Mild ancestor from China
Studies have already revealed that the Sars-CoV-2 virus under the sub-type A2a with D614G mutation has high infectivity, meaning it spreads fast. However, studies have still not shown whether this variant would increase the severity of the infection.
The Kerala study could also trace a growth in virus aggression as it mutated and evolved. One of the 113 samples the study could properly investigate was collected from a Wuhan returnee in January this year. This sample, unlike the others grouped under A2a, was placed under a sub-type called B, which is said to be the virus type from which all other Sars-CoV-2 sub-types have evolved.
Being the ancestral form, this virus did not have the mutation that made the subsequent variants like A2a far more effective in terms of infectivity.
This could also be why Kerala could snuff out the first wave, the Wuhan wave, in no time.
Road to Kerala
The Kerala study has also found that the virus had got introduced to Kerala from Maharashtra, Odisha and Karnataka. Nearly 95 per cent of the Kerala samples had sub-variants unique to these three states: Maharashtra - 35.4 per cent, Odisha - 37.1 per cent; and Karnataka - 22.1 per cent.
"The analysis suggests that the local spread was mostly from cases from inter-state travel and not from imported cases," Dr Chandni said. "It is an indication that foreign returnees were properly screened and isolated," she added.
However, even she admits that the analysis is based on a small sample size. "It looks likely that the A2a clade will be the most dominant in Kerala but studies on samples collected from other pars of the state can reveal the source of infections in these areas. For instance, if studies are done in Thiruvananthapuram, the sub-variants could have a Tamil Nadu connection," Dr Chandni said.
A top government source said that Thiruvananthapuram and Ernakulam medical colleges also have been asked to take up such a gene sequencing study.