Seema Pavgi Upadhye
Viruses constantly change through mutation, and new variants of a virus are expected to occur over time. Sometimes new variants emerge and disappear. Other times, new variants emerge and persist. In 2019 when SARS-CoV-2 burst upon the world, scientists knew that it was bad but thought it was stable as Corona Virus don’t mutate as readily as few other viruses like hepatitis, flu or AIDS.
Coronaviruses are named for the crown-like spikes on their surfaces. They have a molecular “proof reading “ system that SARS-CoV-2 and its generation use to prevent damaging genetic errors when replicating. But virus was indeed bad and was not so stable. This virus after jumping from animals to humans, is acquiring minor random mutations. These mutations can occur as deletion or insertions in genetic code. If this occur, most mutations either kill the virus or cause no change in its structure or behaviour.
But within few months, new variants of original virus or wild type have been seen to cause major changes in the way the pathogen behaves including alterations to its contagious behaviour. Coronavirus scientists monitor changes in the virus, including changes to the spikes on the surface of the virus. These studies, including genetic analyses of the virus, are helping scientists understand how changes to the virus might affect how it spreads and what happens to people who are infected with it.
Multiple variants of the virus that causes COVID-19 have been documented in the United States, South Africa, Brazil and in other countries. These variants seem to spread more easily and quickly than other variants, which may lead to more cases of COVID-19. The mutations are not random and they helped virus to transmit faster and attach the immune system. The people who recovered from COVID 19 were reinfected with the mutant virus.
Here are five of the most prominent variants, listed in the order that researchers first spotted them. This roster identifies where each variant was first seen and gives the technical name or names scientists use to identify it. (Naming variants has caused some confusion because different research teams employ different systems. This list uses one based on the ancestral lineage of each variant, but some variants still have more than one name. The entries also highlight important mutations in each variant—denoted by letters and numbers that indicate their position in the sequence of the viral genome—and describe what scientists know or suspect about what those changes do.
1- The 20A.EU1 variant, first identified in Spain, contains a mutation called A222V on the viral spike protein. The spike is a component of SARS-CoV-2 that binds to a receptor on human cells called ACE2, and this attachment helps the virus get inside those cells and infect them. The spike protein is also the part of the pathogen that is targeted by human antibodies when they fight back against the infection. In lab tests, human antibodies were slightly less effective at neutralizing viruses with the A222V mutation. Over the course of several months, the 20A.EU1 variant became the dominant one in Europe. Epidemiologists never saw any evidence that it was more transmissible than the original. Researchers believe that when Europe began lifting travel restrictions last summer, the variant that was dominant in Spain, spread across the continent.
2-Scientists in the U.K. had been watching the B.1.1.7 variant for some time before announcing in December that it might be at least 50 percent more transmissible than the original form. That announcement was based on epidemiological data that showed the virus rapidly spreading throughout the nation. And it led to international travel bans and stronger lockdown measures in the U.K.The B.1.1.7 variant contains 17 mutations, including several in the spike protein. One of them, N501Y, has been found to help the virus bind more tightly to the ACE2 cellular receptor.It is unclear, however, whether the variant’s enhanced contagiousness comes from N501Y alone or also involves some combination of other spike protein mutations.Despite initial concerns, there has been no real evidence that the variant is more infectious in children than the original, says University of Cambridge microbiologist Sharon Peacock, who is executive director of the COVID-19 Genomics UK (COG-UK) Consortium, a group that analyzes genetic changes to the virus. Recent data from the U.K hint that the variant may be more lethal than the original, but the analyses are preliminary.
3- The B.1.351 variant appeared around the same time as B.1.1.7, and it spread quickly in South Africa to become the dominant version in that country. Like its European counterpart, B.1.351 contains the N501Y mutation, although evidence seems to suggest the two variants arose independently. But scientists are more concerned about another mutation called E484K that appears in the South African version. The genetic change may help the virus evade the immune system and vaccines. It was found that E484K—as well as similar mutations at that particular spot in the protein—made it as much as 10 times more difficult for antibodies to bind to the spike in some people. Late this month researchers in South Africa released a preprint study (research that has not yet been peer-reviewed) showing that an antibody-containing serum from COVID patients was considerably less effective at neutralising this variant.
4 and 5- In January researchers reported they had detected two new variants in Brazil, both descendants of a somewhat older common ancestor variant. Although they share mutations with other newly discovered versions, they appear to have arisen independently of those variants.
Of the two, researchers are currently more concerned about P.1. That variant contains more mutations than P.2 (though both have E484K), and it has already been seen in Japan and other countries. Although it is possible that P.1 accumulated its mutations in an immunocompromised individual. both Brazil and South Africa had large COVID outbreaks in 2020. With so many infected people creating antibodies against the virus, a version that could evade the immune system and reinfect a person who had recovered might have a strong advantage and then become more widespread in a population.
Alarmed by the local outbreaks of B.1.1.7, the variant first discovered in the United Kingdom, the government formed a multi-laboratory network named the Indian SARS-CoV-2 Genomic Consortium (INSACOG) to monitor the evolution of SARS-CoV-2, the virus that causes COVID-19. On March 24, after sequencing less than one percent of coronavirus samples collected by its member laboratories across the country, INSACOG announced it had found “a new double mutant variant.” What alarmed scientists was that the variant carried features from two worrisome lineages; the variants first identified in California (B.1.427 and B.1.429), and those discovered in South Africa (B.1.351) and Brazil (P.1). Although it wasn’t noticed at the time, the mutant had in fact been sequenced and its genetic code deposited in the global database as early as in October 2020, This new variant has spread fast, causing more than 60 percent of all coronavirus infections in the Indian state of Maharashtra alone, which reported the largest number of all COVID-19 cases in India.
The emergence of more transmissible variants highlights limitations in the current state of global surveillance of not only SARS-CoV-2 but of all emerging diseases in far-flung areas. INSACOG was expected to sequence five percent of the positive samples from all states but managed far fewer: only 13,614 by April 15. Certainly, the world has lots and lots of genomic surveillance, and India needs to be doing a much higher proportion. Often people ask how much? The U.K. is the gold standard on genomic surveillance and maybe between five and 10 percent. India does far less than one percent.
Viruses frequently mutate and these mutations occur randomly. In fact, SARS-CoV-2, HIV, and influenza viruses, all of which encode their genetic instructions using the molecule RNA, mutate more frequently than other types of viruses due to copying errors introduced as viruses replicate in their host cells.
More than a million distinct sequences of SARS-CoV-2 have been reported to GISAID, the global public database. Many inconsequential mutations go unnoticed. But some mutations can change the amino acids, which are the building blocks of viral proteins, “which may change their characteristic,”.When one or more mutations persist, they create new variants distinct from the ones already in circulation and are then given new names.
The new variant, now designated as B.1.617 , carries two known mutations; the first at position 452 of the spike protein and the second at 484. It shouldn’t be called double mutation, because that is just a misnomer. Actually, B.1.617 carries 11 other mutations—13 in total, of which seven are in the spike protein that punctuate the surface of SARS-CoV-2 and endow the virus with its signature “crown” structure. The virus uses spike proteins to anchor to the ACE2 receptor protein on the surface of lung and other human cells, and infect them. An eighth mutation in B.1.617 located at the midpoint of the immature spike protein—and also found in some New York variants—can increase the transmission of the virus, giving it an adaptive advantage.
The mutations in the B.1.617 have been studied independently, but not in combination. there’s a lot of mutations coming up in the spike protein. Surface proteins evolve more rapidly, especially with a new virus, as it wants to evolve to bind cells better. Because the spike protein coats the surface of the SARS-CoV-2 virus, it is the primary target for immune system. Immune cells make antibodies that recognize and bind to the virus and “neutralize” it. That is why, all current COVID-19 vaccines also use the spike protein to train the body for immunity.
While random, the mutations in the spike protein that change its appearance and structure can help the virus evade the antibodies. These adaptations increase the ability of the virus to survive and replicate. Any mutations in spike protein have potential to impact the neutralization phenotype of the virus and its infectivity, its transmissibility, and potentially pathogenesis. He has shown that the California variants with L452R mutations are two to three times less susceptible to antibodies from vaccines and convalescent serum samples.
Similar studies suggest that L452R mutation can increase the number of viruses that can infect a single cell, potentially promote viral replication, and help the virus bind more tightly to the ACE2 receptor on the surface of cells. However its not sure whether that mutant can be more dangerous for human population.
Just a mutation at the E484 site alone, which is the case in the B.1.351 and P.1 variants, can help the virus escape neutralizing antibodies . Coupled with the L452R mutation, which is also likely responsible for helping the virus evade antibodies, the B.1.617 can be a very troublesome variant and need to characterize this.
B.1.617 has spread worldwide. On April 3, the B.1.617 variant was identified in a U.S. patient. Could the variant have arisen independently in the United States? No but rather were through global spreads. B.1.617 variant has now been identified in 16 countries on all continents, except Africa.
Since B.1.617 brings so many ominous mutations together, the additive effects seem to be evidenced by the rapid increase in India at present. It should also be noted that the number of viral sequences analyzed in India [about 100 sequence per day] is much smaller than the number of infected people in India [about 300,000 per day]. Therefore, still not sure the current huge surge of COVID in India is due to B.1.617.The so-called fast spreading variant still in the country is about 10 percent so that means 90 percent of the cases in the current sense are something else, not double mutant,” said Rakesh Mishra of the Indian Centre for Cellular and Molecular Biology.
While genomic surveillance of the variants is critical, that alone cannot prevent new outbreaks, super spreader events, or stop the pandemic. Genomic surveillance can only help scientists track where infections are going, and how and where the virus is spreading.
Early in the pandemic there was struggle to test people having COVID, otherwise we cannot know the number of people having COVID and how fast it spreads and the involved risks. Now the next step is genetic sequencing which decodes the genome of SARS-CoV-2 virus in samples from patients. Knowing the genome sequence helps researchers understand two important things – how the virus is mutating into variants and how it’s traveling from person to person. Before the COVID-19 pandemic, this kind of genomic surveillance was reserved mainly for conducting small studies of antibiotic-resistant bacteria, investigating outbreaks and monitoring influenza strains.
Particularly now, as new coronavirus variants of concern continue to emerge, genomic surveillance has an important role to play in helping bring the pandemic under control.
Genome sequencing involves deciphering the order of the nucleotide molecules that spell out a particular virus’s genetic code. For the coronavirus, that genome contains a string of around 30,000 nucleotides. Each time the virus replicates, errors are made. These mistakes in the genetic code are called mutations. Most mutations do not significantly change the function of the virus. Others may be important, particularly when they encode vital elements , such as the coronavirus spike proteins that acts as a key to enter human cells and cause infection. Spike mutations may influence how infectious the virus is, how severe the infection may become, and how well current vaccines protect against it. Researchers are particularly on the lookout for any mutations that distinguish virus specimens from others or match known variants.
Scientists can use the genetic sequences to track how the virus is being transmitted in the community and in health care facilities. For example, if two people have viral sequences with zero or very few differences between them, it suggests the virus was transmitted from one to the other, or from a common source. On the other hand, if there are a lot of differences between the sequences, these two individuals did not catch the virus from each other.
This kind of information lets public health officials tailor interventions and recommendations for the public. Genomic surveillance can also be important in health care settings.
But how do researchers know if variants are emerging and if people should be concerned?
Take the B.1.1.7 variant, first detected in the United Kingdom, which has strong genomic surveillance in place. Public health investigators discovered that a certain sequence with multiple changes, including the spike protein, was on the rise in the U.K. Even amid a national shutdown, this version of the virus was spreading rapidly, more so than its predecessors.
Scientists looked further into this variant’s genome to determine how it was overcoming the distancing recommendations and other public health interventions. They found particular mutations in the spike protein – with names like ∆69-70 and N501Y – that made it easier for the virus to infect human cells. Preliminary research suggests these mutations translated into a higher rate of transmission, meaning that they spread much more easily from person to person than prior strains.
Vaccine developers and other scientists then used this genetic information to test whether the new variants change how well the vaccines work. Fortunately, preliminary research that has not yet been peer-reviewed found that the B.1.1.7 variant remains susceptible to current vaccines. . More worrisome are other variants such as P.1. and B.1.351, first discovered in Brazil and South Africa, respectively, that can evade some antibodies produced by the vaccines.
Detecting variants of concern and developing a public health response to them requires a robust genomic surveillance program. That translates to scientists sequencing virus samples from about 5% of the total number of COVID-19 patients, selected to be representative of the populations most at risk from the disease. Without this genomic information, new variants may spread rampantly and undetected through the country and globally.
Laboratories must collect the samples, often from different sources: public health labs, hospitals, clinics, private testing labs. Once the sequencing test is performed, bioinformaticians use advanced programs to identify important mutations. Next, public health professionals merge the genomic data with the epidemiological data to determine how the virus is spreading. All of this requires investment in training people to perform these tasks as a team.
Ultimately, to be useful, a successful genomic surveillance program must be fast and the data needs to be made publicly available immediately to inform real-time decision-making by public health officials and vaccine manufacturers. Such a program is one of the public health tools that will help bring the current pandemic under control and make a set up to be able to respond to future pandemics.
References
Alexander Sundermann, Understanding Genomic Surveillance: What Is It?5/4/2021The Conversation
SANJAY MISHRA. This ‘double mutant’ variant is adding fuel to India’s COVID-19 crisis. Science coronavirus coverage. 28/4/2021,
Sara Reardon. The Most Worrying Mutations in Five Emerging Coronavirus Variants. Scientific American 29/1/2021
Stuart Ray and Robert Bollinger New Variants of coronavirus: what you should know. John Hopkins COVID 19 updates-2021
