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OPINION
What You Need to Know About the Coronavirus Variants
BDy DR. ARMANDO PAEZ
espite leading the world in COVID-19 infec-
tions and being well-equipped with an unsur-
passed genome-sequencing infrastructure, the U.S. found itself in the unfortunate position of falling well behind other countries in sequencing coronavirus genomes and getting ahead of emerging variants.
Now back on track and identifying variants that have begun in the U.S., including in New York and California, scientists are increasing their COVID-19 sequencing efforts as many ask, “should I be worried about the variants?”
Let’s discuss some pressing questions about what role the variants are playing in the ongoing pandemic.
Q: Are the coronavirus variants that have emerged over the past few months a cause of concern for epidemiologists?
A: Any time a new variant of the novel coronavirus SARSCoV2 is discovered, there is cause for concern. The major variants reported not only in the U.S., but also in other parts of the world — B.1.1.7 (U.K.), B.1.351 (South Africa), and P.1 (Brazil) — are found to be more infectious that the original SARSCoV2 strain. More recently, home- grown variants — B.1.526 from New York City and Cali- fornia variant B.1.427/B.1.429 — have also been reported. Any of the variants can become the circulating strain in a population and can spread easily to others in a geometric fashion. This carries significant public-health importance and urgency as more people can get sick at the same time and overwhelm the healthcare system. Scientists are still studying these variants and are also on the lookout for new ones that are emerging.
More recently, the U.K. variant, thought to be just easily transmissible, is now associated with a higher risk of dying from COVID-19 based on a peer-reviewed study. Depending on the variant, the mutations (changes in the genetic code) can confer resistance to some available COVID-19 treat- ments. For example, bamlanivimab, a COVID-19 monoclo- nal antibody authorized for the treatment of mild-moderate COVID-19, is thought to be ineffective against the South Africa variant. Thus, the variants also carry clinical impor- tance for COVID-19 patients. However, not all COVID-19 treatments may be significantly impacted by the variants. For example, mutations identified in these new variants have not significantly changed the part of the virus targeted by remde- sivir, an FDA-approved drug for severe COVID-19.
Q: What do these new variants from the U.K., South Africa, and Brazil, as well as those that have originated in the U.S., share in common, and what makes them different from the original COVID-19?
A: All five of these variants mentioned above have muta- tions in the spike protein that allow them to better latch onto and infect human cells, making them more transmis- sible (up to 50% more). All these variants have now been detected in the U.S., and, according to the Centers for Disease Control and Prevention (CDC), the U.K. variant is expected to become the dominant strain in the U.S. by the end of March.
Early on, South African researchers believed their variant could evade antibodies produced by the immune system.
This can imply possible reinfection to occur as the antibod- ies cannot neutralize the variant virus. This was seen in the Brazil variant. Scientists continue to study how these vari- ants can potentially evade immunity to COVID-19.
Q: Are the new variants more deadly?
A: This is an evolving story. Initially, scientists thought there was no evidence that the infection from any of the variants is more deadly than the old strain. A recent study suggests there is an association of the U.K. variant with higher risk of dying from COVID-19. I expect that more information will be available regarding the other variants in the near future.
Q: Why did it take a while before we began to see differ- ent variants of the coronavirus?
A: Viruses such as SARSCoV2, the virus behind CO- VID-19, naturally mutate, and viral variants occur. Many variants emerge and disappear, but some persist because their accumulated mutations offer a ‘survival of the fittest’ advantage among others over time to become the dominant circulating virus.
Q: Is there a difference between a variant of the virus and a mutation, and which is more problematic?
A: A viral mutation refers to specific changes or alterations in the gene of the virus. This is a natural occurrence in the life of a virus, particularly an RNA virus like the coronavirus. Some mutations do not change how the virus behaves, but some do affect its characteristics related to its ability to at- tach to the host cell, for example. This can potentially confer higher risk of transmission of infection given a number of viral particles compared to the old strain.
A variant refers to a virus with slight changes in the genetic codes due to these mutations. Depending on the effect on how the virus behaves due to the genetic changes, whether a single mutation or a combination of mutations, it may or may not be problematic. It can be problematic to the host, but offers an advantage to the virus to survive. A variant may become the dominant strain because of its sur- vival advantage in a given environment. It is also important to remember that, if there are more viral replications oc- curring — let us say, more infections in the community — there is a greater chance for more mutations to occur. That is why interrupting the cycle of transmission can lessen the chance of variants to occur.
Q: Why are these variants more easily transmissible?
A: The variants have mutations in the spike protein en- abling them to latch on and infect human cells more easily. Many of these mutations are in the receptor binding do- main of the virus. The mutation E484K, common in these variants, can increase the affinity of viral protein with its receptor, thus explaining its ability to be easily transmitted.
Q: Since these variants are more transmissible, does that mean the recommended safety precautions will no longer work to prevent spread of the virus?
A: Currently recommended safety precautions — vacci- nation, social distancing, mask wearing, handwashing, and isolation and quarantine — should still work in preventing
infections from these variants. Again, if these variants are not given a chance to replicate, they will have less chance to further evolve and survive in the community.
Q: If the same precautions are enough, why do scien- tists say more people could become infected in the months ahead?
A: Vaccine rollout in the U.S. is now making progress, but we are not yet at the level of herd immunity, estimated to be 60-70% either by natural infection or vaccination. Since these variants are more transmissible, if the public is not compliant with recommended safety measures, more exposures and infections will easily occur. The increased number of cases will put more strain on healthcare resources, lead to more hospitalizations, and potentially cause more deaths.
Q: Will the currently available vaccines protect against the variants?
A: Based on the most recent evidence, the currently available COVID-19 vaccines can still broadly protect you, albeit at differing levels of efficacy, from the five circulating variants. The South Africa variant more significantly im- pacts efficacy of the available vaccines. The New York strain appears to have a similar effect, but much less so. Recent reports also suggest these variants may evade immunity from natural infection or escape the antibodies from previ- ous infections. Similarly, this can impact the efficacy of the COVID-19 monoclonal antibodies authorized to treat CO- VID-19. This is closely being investigated, and hopefully, more information will be available in the near future.
Q: What is not known about the variants?
A: We still do not have a complete picture of how widespread these variants are in the U.S. and around the world. The CDC is now closely monitoring this, as it has huge implications epidemiologically. As mentioned above, these can affect future decisions and interventions in order to curb the pandemic. For example, vaccine designs and booster shots are already being discussed in order to get ahead of the circulating variants.
Q: Do we expect other variants to surface?
A: Yes, expect more variants to occur in the future unless we stop the circulation of the virus in the community. As mentioned above, if there is less viral replication, there is less chance for viral mutations, hence variants, to occur.
Q: Will the new variants prolong the pandemic?
A: The new and emerging variants can potentially prolong the pandemic because of their ability to be more easily transmitted. This will also depend on other factors, such as compliance of the communities to public infection- control measures, our ability to detect these variants, the vaccination rates in the community affecting the chance
of achieving herd immunity sooner than later, the risk of reinfection, and availability of effective treatments against the new variants. -
Dr. Armando Paez is chief of the Infectious Disease Division at Baystate Health.
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