Coronavirus: In Maharashtra, mutation raises infectivity concerns

The findings of the study, if established, could explain the surge of cases in the western state, not just in capital Mumbai , but in other cities such as Pune and Nagpur as well.

One of the two mutations feared to have spread rapidly in Maharashtra may have the ability to make the Sars-Cov-2 more adept at infecting humans, improve its ability to multiply within a host and possibly escape a more complex part of the human immune response, a new study awaiting peer review suggests.

A heath worker conducts Covid-19 testing of a man at Dadar market, amid a surge in coronavirus cases across Maharashtra, in Mumbai. (HT file photo)

The findings, if established, could explain the surge of cases in the western state, not just in capital Mumbai , but in other cities such as Pune and Nagpur as well.

The findings relate to the mutation known as L452R, which is one of the two “double mutations” the Indian government said was detected in large numbers in parts of Maharashtra. The state is by far the worst-hit region in India, with an exponential rise in infections that has forced authorities to bring back lockdown-like curbs.

Till now, little has been known about this mutation in particular, although it is part of the variant that has triggered a similarly serious wave of infections in California.

Now, a team led by researchers from Japan has found the L452R mutation can “potentially increase viral infectivity” and escape from what is known as HLA-A24-restricted immunity, which refers to action by adaptive immunity in the human body.

“Frankly speaking, these two findings mean the L452R can be more dangerous than prototype (the predominant Sars-Cov-2 variant), particularly for people harbouring HLA-A24 type,” said Kei Sato, one of the authors and professor, Institute of Medical Science, University of Tokyo, in an e-mail exchange.

HLA-A24 refers to a particular gene that some people carry, and the authors note that it is most commonly found in populations in East and Southeast Asian countries. It tends to influence how cellular immunity works in some people, which in this case appears to be hindered in the context of a Sars-Cov-2 infection.

The study, based on laboratory experiments, showed L452R conferred multiple properties: it appeared to make the S protein (which the virus uses to latch on to human cells) more stable, it enhanced affinity to ACE2 (the receptor or doorway the virus uses to enter cells), and it seemed to enhance how the virus multiplied.

Immune response to a pathogen such as Sars-Cov-2 typically has multiple levels, including antibodies that bind to the virus and stop it from infecting people and killer T cells that destroy infected cells.

The HLA-restricted immunity influences the mechanism of killer T cells, which may be crucial since research has separately established a link between the timing and nature of immune response with how severe the disease becomes for someone: often, those with serious or fatal Covid-19 have a delayed immune response.

“Therefore, it is conceivable to assume that the HLA-restricted CTLs (cytotoxic T cells, or killer T cells) play crucial roles in controlling SARS-CoV-2 infections and Covid-19 disorders,” the authors note in their study.

This is not the first time a particular Sars-Cov-2 mutation is shown to be evading some component of the cellular immunity, but it is the first time a widely spreading mutation has been shown to demonstrate that characteristic.

Sato said the team will next evaluate how this mutation could influence immunity conferred by vaccines.

To be sure, how the variant in Maharashtra behaves will require tests and epidemiological analysis involving that variant itself. A variant also includes multiple mutation, and these can combine to add or remove particular characteristics to the Sars-Cov-2.