A variant of the SARS-CoV-2 virus with two key mutations has been recently identified in California. The existence of this particular variant was first reported from India and is believed to be responsible for the recent surge in COVID-19 cases in Maharashtra, after months of declining cases. The existence of the ‘double mutant’ was first confirmed by India’s Ministry of Health and Family Welfare on March 24, 2021, and a day later researchers at Stanford University identified its presence in a coronavirus sample taken from a patient in San Francisco bay area. Since then, experts have identified a total of five cases of infections due to this variant in California.
The ‘double mutant’ exhibits two separate spike protein substitutions on its gene, at the E484Q and L452R positions. (For a non-expert’s guide to what these alpha-numerical terms mean, see here.) The resulting changes in the spike protein’s structure confer improved infectivity, virulence, and/or the ability to escape neutralizing antibodies in the human body. There is sufficient evidence of how these mutations behave separately – but what we know about how they work together is limited.
In previously identified variants of concern (20C/S:452R and 20C/S:452R), the L452R mutation has been known to exhibit improved binding of the virus to host cells and increased ability to escape from antibodies. Scientists have found that the mutations E484K, E484Q, and E484P (identified in the 20I/501Y.V1 and 20J/501Y.V3 variants) were related to reduced serum-antibody binding and greatly reduced viral neutralization.
These mutations have also significantly mitigated neutralization by some, but not all, emergency-use monoclonal antibody drugs. For example, given the widespread emergence of variant strains across the US, the country’s Department of Health and Human Services and Eli Lilly and Co. released an emergency update on March 24 urging medical workers to stop distributing a monoclonal antibody called bamlanivimab as treatment of COVID-19.
So it is reasonable to expect that the presence of these two mutations together could confer increased virulence and infectivity to the virus. There are also concerns about how effective existing vaccines may be in protecting against the new variant, even if it is too soon to predict the course of the variant through the population. Scientists need to undertake more epidemiological studies to identify the outcomes of these and other coexistent mutations.
The emergence of new strains of the novel coronavirus is a matter of concern and should prompt public health agencies to pick up the pace in tackling the pandemic. Both scientists and government officials must continue efforts to fight pandemic fatigue, improve public health precautions and expand global immunization efforts inequitable fashion. Every missed chance to vaccinate the community is an opportunity for the virus to transmit, replicate and mutate.
India’s Ministry of Health and Family Welfare in India hasn’t yet acknowledged the epidemiological linkage of this ‘double mutant’ variant to the rising number of COVID-19 cases. A ministry statement only said, “Though [variants of concern] and a new ‘double mutant’ variant have been found in India, these have not been detected in numbers sufficient to either establish or direct relationship or explain the rapid increase in cases in some states.”
This may be reasonably provided the limitations in genomic sequencing and epidemiological investigations available. But the virus’s intercontinental migration means we need to double down on efforts to identify and study the hand of new variants in India’s newly skyrocketing caseload. This would mean improving the national capacity for genomic sequencing, epidemiological surveillance, health informatics, equitable vaccination efforts, and public health preparedness.
Lekshmi Rita Venugopal is an epidemiologist and public health professional from the University of California, Berkeley.
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