What is India going through?

Did the double mutant help set a world record?

Photo by Aakanksha Panwar on Unsplash

ndia ranked highest in the world with its daily cases reaching as high as 3,14,835 last Thursday(22/04/2021). As the second wave mercilessly crashes through the country breaking the healthcare system and eating up the crematoriums, the people let out their loudest cry for help. Several questions are unclear as the data are not disclosed publicly, although several doctors and scientists report that they observe a different trend in the cases during the second wave. Several youngsters seem to be infected, doctors in Delhi report that unlike the first wave most people getting hospitalised are in their 30s, and more deaths were seen in people without any comorbidities.

India had 10 lakh active cases during the last peak but now the reports show 14 lakh active cases. Although many hospitals and doctors say that children are showing serious infections there are no connections yet showing that the rate of infection (no. of children being infected) is higher now than before. Many doctors say that there is a possibility that the number of children who tested positive in the first wave were overlooked because most of them were asymptomatic.

Children are definitely more symptomatic now than what we saw in the first wave,” Tanu Singhal, a pediatrician and infectious disease specialist at Mumbai’s Kokilaben Dhirubhai Ambani Hospital, told the Hindustan Times. “The severity of their illness has gone up.”

Some children had to be hospitalised in Mumbai for gastrointestinal infections, breathlessness, and fever — all linked to the virus. “Those with gastrointestinal infections had to be put on intravenous fluids,” paediatrician Bakul Parekh told Hindustan Times. “The patients who were breathless required steroids and oxygen support.”

What is the reason for the surge?

There is no one particular reason for the surge, there are many. The number one reason being the complete negligence in following social distancing guidelines and protective measures once there was a decrease in the cases. Another reason is that India, despite manufacturing huge proportions of the world’s vaccine supply, failed to vaccinate its population when there was a decrease in cases and the hospitals and nurses had time to spare to safely administer the vaccine.

The double mutant strain of the virus definitely has an important impact on the cases, but taking in to consideration the aforementioned reasons, and the general lack of statistics related to the strain, there is no surety that the mutant virus is the number one cause of the surge.

To add to this trying situation, India now has another mutant strain derived from the Β.1.617 strain called the triple mutant or B.1.618. This strain is found in samples from Bengal, Maharashtra and New Delhi, even little data is available on this virus, all we have so far are speculations.

What do we know about the mutant strain?

The strain of virus that is of concern in India is called B.1.617, this strain, however, is not a new mutant, it was first entered into the global genome database as early as Oct 2020. India reported having sequenced the highest number of this viral genome, followed by the UK and then by the US. There might be a small bias in the data based simply on the fact that the country that has performed higher sequencing would have detected a higher number of the B.1.617 strain.

How worrying are the constant mutations in the virus?

The nature of any virus is to mutate. The reason behind this is evolution through natural selection, just as any living being evolves by natural selection, viruses do too.

The aim of the human immune system is to defend the body from pathogens, similarly the aim of the pathogen is to come up with new ways to evade the immune system, reproduce and infect more hosts. In order to meet this aim, every time the virus replicates the characteristics that help evade the immune system are restored, and the characteristics that negatively affect their spread and evasion are left behind. It is also interesting to note that the aim of the virus is never to kill the host (as they require a host to reproduce and spread), if the host is dead then the virus has no means of transmission, hence ideally as the virus evolves it would aim to increase its infectiousness and decrease its fatality rates.

During replication, all cells that have DNA as the genetic material have a special proofreading tool that prevents mistakes from happening while the genetic code is copied from the parent genome to the daughter. Whereas cells with RNA as the genetic material lack the proofreading tool, which leads to many mistakes during copying of the parent genome. These changes result in the formation of different proteins, thereby altering the characteristics of the virus, making it more or less infectious.

Photo by CDC on Unsplash

Mutations to be noted in the two variants.

The B.1.617 strain has 13 mutations as compared to the original strain (hence calling it double mutant isn’t very accurate), the most notable mutation in this is the E494Q and L452R.

The E494Q mutation also called the escape mutation occurs in the 484th position of the genome, the UK, South African and the Brazil variant also have a similar mutation in the 484th position their mutation is E484K instead.This mutation is known to help the virus slip past the human immune response

Despite having the escape functionality, not much statisitc information is available on the E494Q mutation except for few studies that show a reduction of neutralization (inactivation of the virus by antibodies) by some but not all convalescent plasma taken from people who were tested positive naturally for SARS-CoV-2.

The other major mutation found in the B.1.617 strain — L452R, is also found in few other variants like B.1.429 (California strain). It is predicted to increase the viral infectivity and its host immune evasion potency. Experts report weaker neutralization of the virus by convalescent plasma and also by monoclonal antibodies in lab experiments.

The P681R or P681H which is found in various strains like B.1.617, B.1.318 B.1.1.7 is found next to the furin cleavage sites on the spike protein (which is said to be responsible for the virus’s relatively high infectivity). This mutation could lead to a change in the spike protein processing or other activities of the virus, although more information is essential to understand for sure the changes brought by this combination of mutations.

The major mutations in the B.1.618 or the triple mutant are:

  1. A deletion and two changes in spike protein
  2. Deletion of H146 and Y145
  3. Mutation in E484K and D614G in spike protein

Is B.1.617 a variant of concern?

The criteria for a mutant strain to be considered a variant of concern(VoC) is if it has:

1)increased transmissibility or virulence

2) a decrease in the effectiveness of vaccines, treatments, diagnostic assays, or other public health measures.

3) escaped from immunity derived from natural infection.

This variant is currently classified as a variant under investigation by the Public health England, this means the virus has highly certain predictable data that it has undergone mutations that cause adverse effects, but still doesn’t meet the definition of a variant of concern.

Despite having several qualities of a VoC, there hasn't been much time to investigate the viral capabilities in a lab. It also takes some more time to study evidence from real-world vaccination reports. which is why we can’t be certainly sure if this strain is the cause of the surge or if it is merely co-incidental that the surge and the spread of the strain happened at the same time. It is essential to confirm if there was indeed a cause and effect relationship before declaring the strain as a VoC, which is difficult to do currently as there has been only 1000 sequences submitted by India, out of 4 million cases. Also this strain was detected back in 2020, therefore if it is just catching momentum now, then chances are that it isn’t as transmissible as the other variants of concern.

Immunology graduate

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