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How dangerous is India’s ‘double mutant’ COVID-19 variant?

It is beginning to feel as though not a week can go by without scientists identifying a new variant of the coronavirus. Each time a new strain is announced, I feel myself becoming increasingly numb to the shock factor that the headline is supposed to trigger.

I have written extensively about variants originating in the United Kingdom, Brazil, South Africa and New York; this week, it is the turn of India.

In late March, India’s National Centre for Disease Control (NCDC), a division of the Ministry of Health and Family Welfare, announced that a new variant – dubbed a “double mutant” – had been identified in samples of saliva taken from people in Maharashtra, Delhi and Punjab. This comes on the back of a month that has seen a surge in cases of COVID-19 across India, with many states re-imposing curfews, restrictions and lockdown measures.

The Ministry of Health and Family Welfare says this new “double mutant” variant has not been found in sufficient numbers to account for the increase in COVID-19 cases across the country. That, rather, is thought to be due to large public gatherings such as weddings, the opening of cinema halls and gyms, as well as large political rallies in West Bengal where elections are due to be held soon.

Nevertheless, it is a “variant of concern” (VOC) and is being closely monitored. The genome sequencing carried out by a consortium of 10 labs in India, called the Indian SARS-CoV-2 Consortium on Genomics (INSACOG), has identified two important mutations in the new variant, giving it the unfortunate title of “double mutant”.

First, the E484Q mutation, which is similar to the E484K mutation identified on the Brazilian and South African variants, can change parts of the coronavirus spike protein. The spike protein forms part of the coronavirus outer layer and is what the virus uses to make contact with human cells, bind to them, then enter and infect them.

The vaccines have been designed to create antibodies which target the spike protein of the virus specifically. The worry is that if a mutation changes the shape of the spike protein significantly then the antibodies may not be able to recognise and neutralise the virus effectively. Scientists are investigating whether this may be the case for the E484Q mutation.

The second is the L452R mutation, which has also been found in a variant thought to be responsible for outbreaks in California. Scientists believe this mutation increases the spike protein’s ability to bind to human host cells, thereby increasing its infectivity. The study also suggests this mutation may aid the virus in evading the neutralising antibodies that both the vaccine and previous infection can produce, though this is still being investigated.

The combination of these two mutations would indeed make the variant a concern if it was to become the dominant variant across India.

Right now, however, all eyes are on the UK B117 variant, which possesses the N501Y mutation making it up to 60 percent more infective, and which has been found extensively in India as well. It has been identified in 125 countries worldwide and is now the dominant variant in the UK.

The NCDC said 81 percent of 401 samples sent for genome sequencing from Punjab were found to have the UK variant and there is real concern among scientists that this variant may not only become the dominant variant in India, but may be contributing to the increasing number of infections.

They are urging the Indian authorities to scale up genome sequencing to quickly identify new variants that can potentially be more dangerous, and then isolate individuals who are known to be infected as well as their close contacts. Although the situation in India’s hospitals is much better now, memories of the intensity of the first wave loom large among healthcare workers. The country is at an important point in the pandemic – one that will require decisive action by the government and a willingness by the Indian population to prevent a national surge in new cases.

While it is important that we keep analysing the virus for new mutations, especially those that may allow it to evade the vaccines, it is also important to know that mutations are common during viral replication and new variants are to be expected.

It is also good to know that the companies which make the vaccines will be able to “tweak” their vaccines to adjust for new variants, a process that will take a relatively short amount of time.

In fact, the UK has already announced potential booster shots for the autumn using vaccines that have been tweaked to be more effective against new variants, and this is likely to happen worldwide. We do it for the flu vaccine every year; it may become customary to do the same for the COVID-19 vaccine.

Pregnant and lactating women were not included as a group in the trials for any of the vaccines (although some women became pregnant after the trials commenced). However, since vaccination programmes have begun, scientists have been able to determine that the vaccines are most likely safe for both pregnant and lactating women. The general advice to pregnant women is to take up the vaccine, especially if they work in a role that is public-facing or have an underlying health condition that puts them at risk of developing complications should they contract the coronavirus.

There has been some debate about how a pregnant woman’s body might respond to having the vaccine at a time when their immune systems may be suppressed to stop it “rejecting” the baby.

A study by Harvard University, published in the American Journal of Obstetrics and Gynaecology, examined responses to vaccines in 131 women (84 pregnant, 31 lactating and 16 non-pregnant). They were given the full two doses of either the Pfizer or Moderna COVID-19 vaccines and antibody levels were checked in maternal blood and breast milk before the study, at the time of the second dose and then again two to six weeks after the second dose.

In those women who were pregnant, baby umbilical cord blood was also tested after delivery for the presence of maternal antibodies triggered by the vaccine. The study also compared these antibody levels with a group of women who had previously been infected by COVID-19.

The results showed that women – whether they were pregnant, breastfeeding or neither – had similar levels of antibodies after the two vaccine doses.

Vaccine-generated antibodies were present in all umbilical cord blood and breast milk samples. The second dose increased specific antibodies, called immunoglobulin G (IgG). These form the basis of long-term protection against the virus; they are retained and reproduce rapidly when exposed to the real virus, neutralising it before it has a chance to take hold and cause a full-blown infection. Importantly, side effects from the vaccines were rare and equally reported in all three groups of women.

When vaccine-induced antibody levels were compared with those of women who had antibodies because of a previous infection of COVID-19, they were found to be higher. This means the vaccines are more likely to provide more robust and longer-lasting protection against coronavirus in the future compared with any protection gained through a previous infection.

The study does provide some reassurance to women who are pregnant or breastfeeding and worried about getting the vaccine. The sample size is relatively small and more research will be needed to back this study up, but it adds to the growing data proving the safety of the vaccines.

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