India is currently experiencing a very high rate of infections across the country, resulting in record hospitalizations, ICU admissions, and now a severe shortage of oxygen. How did this happen?

COVID 19 Mutations: an update

India is currently experiencing a very high rate of infections across the country, resulting in record hospitalisations, ICU admissions and now a severe shortage of oxygen. How did this happen? As with all things, it is likely multifactorial, and blame cannot be associated with one single issue. Socioeconomic issues preventing effective lockdown, stretched healthcare resources, poor communication and maintenance of social distancing and mask use. And of course, viral variants, something we will be discussing below.

GENETIC MUTATIONS

Mutations are integrated deeply into the backbone of genetics. When DNA replicates, its two strands split apart and are used as blueprints to create two new strands, each containing half the original DNA. Mutation’s sneak into the replication phase, and can change the proteins the DNA encodes. If these mutations are compatible with life, they survive and may be passed down the generations. If the mutations provide an evolutionary benefit that improves the survival of the organism and allows it to outcompete other organisms, its descendants will survive, and the mutation will flourish.

Complex organisms such as plants and animals have inherent DNA repair mechanisms that reduce the rate of mutations. This is because most mutations are incompatible with life, as they destroy critical proteins required for the most basic functions of cell function and life. Cancer is evidence of what happens when these repair mechanisms fail. Viruses do not have such protection; when the high mutation rate is combined with the high replication rate, viral variants are inevitable.  

 

COVID MUTATIONS

Scientists have been tracking mutations of the SARS-CoV-2 virus closely. Countries across the world are basing the re-opening and recovery of their societies on reducing infection rates and preventing re-infections through vaccination programmes. If the virus mutates, it can result in increased infectivity, mortality, and potentially the ability to escape from natural immunity offered by antibodies.

Indian genome scientists first detected the “double variant” of the novel coronavirus in October 2020, and in the UK in Feb 2021. It has been on the rise, and B.1.617 accounts for almost 70% of genomes submitted by India to the global database GISAID. It has a total of 13 mutations, which in turn lead to the change in multiple amino acids. B.1.617 has multiple mutations and describing it as a “double mutant” virus is therefore inaccurate.

 

L452R

B1617 s more contagious because of a mutation in the spike protein known as L452R.This mutation has been studied as it has also been found in variants identified in California (including apes in San Diego Zoo).  It is thought this improves the binding to the ACE2 receptors in the lung and may also have some ability to escape from neutralising antibodies.

 

E484Q

The second mutation is E484Q, which also affects the spike protein to make it less susceptible to pre-existing antibodies, though there is limited evidence for this. Looking at convalescent plasma donated by people it appears to have weaker neutralisation of B.1.617 in some people, though this isn’t a consistent finding.

Mutations at position 484 have also been found in other global variants, though these E484K mutations lead to different functions. One study looking at the UK B.1.1.7 variant looked at how this E484K mutation affected viral interactions in vaccinated patients. Patients who have been vaccinated produce antibodies with a wide range of actions targeting multiple sections of the spike protein. When these patient serums were exposed to the B.1.1.7 mutation, it was found to have decreased neutralisation. This raised the risk of reduced vaccine efficacy and threatened the vaccine programme. Currently, public health officials are confident our vaccine programmes cover the emerging variants. 

 

CONCERNS

Whilst B.1.617 is concerning, it currently accounts for about 20% of cases in Maharashtra, and likely a low percentage of total infections in the country. There is not yet enough evidence to classify it as a “variant of concern”, and further research is required. Though it has increased potential for spreading, currently the UK variant B.1.1.7 may be on the rise, and more concerning. It has over 50% increased transmissibility and 60% lethality and contributed to the UK’s most recent wave of infections. Genomic studies have shown it is now the dominant form of the virus in the Indian state of Punjab.

What is most concerning, however, is the risk of more variants emerging. As the infection spreads unimpeded through the population, viral replication remains at an all-time high, which in turn increases the risk of mutations. Current mutations are covered by vaccines, future mutations may not be. This is why we need to lower infection rates as soon as possible.

Social distancing, use of masks, vaccinations, lockdowns, and quarantine when expressing symptoms.  We have to follow public health advice, to prevent our infection rates from spiralling further out of control