Study on Gujarat’s population: Two mutations in two genes linked with mortality in Covid patients

One of the researchers of the study explained that this study is only a preliminary analysis aimed at “live-tracking” the virus as the pandemic evolves and the mutations observed at this point is only pertaining to the virus’s genome. The way forward from here, as the researchers mentioned, would then include studying the host genome, followed by the interaction of the virus genome with the host genome and subsequently understanding how novel coronavirus proteins interact with the target, that is the human body and its organs.

While the researchers remain cautious of drawing any correlation of genomic mutations with mortality, as one of them said, it “would only be an exaggeration at this point,” the study has identified that the mutations were statistically significant with the mortality rate in the age group of 41-60 years, with respect to Gujarat.

“The Gujarat-specific mutations become significant in terms of how we may have to focus our diagnostic intervention or treatment intervention, or even how the vaccine may be rendered defunct, if these mutations are not accounted for. The mutations prevalent worldwide or even all over India, will get taken care of otherwise,” said one of the researchers.

The study noted that the two mutations were present in two genes – Orf3a and N. The former involves the protein affecting regulation of inflammation, antiviral responses and cellular changes or death. These two mutations were also found to be significantly associated in the samples of the 43 deceased Gujarat patients. The N-gene mutation is forming a distinct sub-cluster in Gujarat, India and globally, in the sample size studied, the study noted.

Published as a pre-print and yet to be peer reviewed, the study has been authored by 15 researchers – 13 from GBRC, including its director professor Chaitanya Joshi, one from the Gujarat State Biotechnology Mission and one from IIT Guwahati. The study was funded by the Department of Science and Technology of the Gujarat government, while no competing interests were declared in the paper.

Samples were collected on the basis of Covid-19 incidence rate from across the state from 13 originating labs representing a total of 38 geographical locations from 18 districts in the state. At least 243 of these were taken from the three districts of Ahmedabad, Surat, and Vadodara, while 64 other samples were taken from the districts of Sabarkantha, Rajkot and Gandhinagar.

The primary focus was on missense mutations as these kinds of mutations change the protein structure, affect the functionality and how the disease may manifest in the body. Identifying dominant and statistically significant mutations prevalent in the Gujarat patient genomes, these missense mutations were observed in the spike protein of the coronavirus genome, which attaches itself to the ACE-2 receptor in the lungs.

While the effect of mutations can be studied better through cell culture (In-vitro), in a biosafety level -3 laboratory, there is no such facility in Gujarat. A second option remains to study it in live patients (in-viva), but that remains unfeasible amidst the pandemic. The third best option then remains analysing the genomic sequences with the metadata of patients such as age, sex, treatment status etc. and looking at plausible correlation, one of the researchers said while explaining why the particular method was chosen.