In the past few months, senior public health officials in the US, including CDC (Centers for Disease Control and Prevention) director Rochelle Walensky and head of the National Institute of Allergy and Infectious Diseases Anthony Fauci, have warned of “disturbing," “tenuous,” and “precarious” new trends in the COVID-19 pandemic. 

They caution that premature relaxation of restrictions could have devastating consequences because multiple emergent variants of SARS-CoV-2 virus still have the possibility to drive new surges of infection. These statements may at first seem counterintuitive or overly pessimistic. Many national mass vaccination campaigns are well underway (at least in wealthy countries), and recent research shows up to 90 percent effectiveness in real world settings for the Pfizer/BioNTech mRNA vaccine. So why should there still be so much concern?

Though enormous progress has been made in science and policy since the SARS-CoV-2 virus was first detected in late 2019, there remain valid warnings about emergence of viral variants. Global technology and human society are not the only things that have changed since December 2019. The virus itself has also evolved during this time, and with over 140 million global infections to date, there have been many opportunities for viral mutation. After over a year of the pandemic, people are tired. But as much as people wish to finally be done with this virus, we remain in something like a “race” between getting people vaccinated and new variant-driven surges.

It is not possible to know exactly how many variants there are out there, but there are many organizations working to sequence and catalogue them as fast as they can. Variants can now be tracked geographically, through evolutionary history, by particular mutation, and as reported in the world over time. Out of the many, the CDC has identified five variants of concern, which include B.1.351 (first identified in South Africa), B.1.1.7 (first identified in the UK), P.1 (first identified in Brazil and Japan), and B.1.427/B.1.429 (both first identified in California, USA). In order to reach this level of concern, a variant must show evidence of increased transmissibility, increased disease severity, or evidence of impact on diagnostics, treatments, and vaccines. 

The most salient form of genetic mutation found in these variants involves changes to the spike protein (S protein), which is important because S proteins are the main protein type used as a target in COVID-19 vaccines currently being used, regardless of underlying technology, including vaccines based on mRNA (BioNTech/Pfizer, Moderna/NIAID), DNA and viral vectors (AstraZeneca/Oxford, Johnson & Johnson), or protein subunits (Novavax, others under development).

The most alarming variant may be the B.1.351 (S.501Y.V2), which was first identified in South Africa. A recent study reported on the preprint server medRxiv suggests that vaccinated people in Israel who were infected at least a week after the second dose were disproportionally infected with B.1.351 versus the more common B.1.1.7 variant. 

This isn't a reason to panic; these results have not yet been peer reviewed, and only 1 percent of the study population was infected with the B.1.351 variant, which the authors describe as their “main caveat.” Nevertheless, there is also additional evidence to note, including a research finding that two doses of the AstraZeneca/Oxford vaccine are ineffective against mild-to-moderate infections with the B.1.351 variant, and real-world observations of the same phenomenon. More research is necessary to determine the extent to which this variant may evade current vaccines.

These troubling trends are associated with the particular combination of mutations found in B.1.351. The N501Y and K417 mutations are thought to help the virus latch on tighter to human cells, and one or both of these mutations appear in many different viral variants. The E484K mutation is also particularly concerning, because it is thought to help the virus evade the body’s immune defenses, which is likely to increase the risk of reinfection. This mutation might also explain an important mechanism of vaccine evasion, and it is also found in the P.1 variant, which was first identified in travelers from Brazil.

The news for the B.1.1.7 variant is more encouraging because there is increasing evidence that the mRNA vaccines are effective at inducing neutralizing antibodies against this strain. B.1.1.7 moved rapidly through the UK and beyond, suggesting it is more infectious than the original strain, and it has multiple mutations to the spike protein including N501Y, though it lacks the E484K mutation. 

The B.1.427/B.1.429 variants, first identified in California, are eliciting increasing concern from scientists. Another preprint study reports that these variants are more transmissible and cause increased viral shedding (how much virus a person expels from their body) compared to early strains of SARS-CoV-2. The study also finds that they may interfere with vaccine efficacy and are behind multiple outbreaks in California. In these variants, a different spike protein mutation (L452R) may weaken the binding of antibodies to viral spike proteins.

With ongoing uncertainty about viral variants and their potential to lessen the impact of mass vaccination campaigns, public health officials still recommend precautions such as wearing masks and limiting the size of indoor gatherings, even for those already vaccinated. The potential for unexpected developments, such as the recent “pause” in the use of the Johnson & Johnson vaccine in the US, only increases the level of uncertainty. 

Finally, it is important to remember that the virus is still evolving, and new variants may emerge at any time. New variants can proliferate in under-vaccinated groups including children, disabled people, and in the many countries that lack sufficient resources, where there is often little or no access to any vaccine. Possible plans to delay second doses in order to more rapidly vaccinate others with a first dose could have the unintended consequence of fostering the conditions in which viral evolution is favored, potentially leading to new variants of concern.

Based on the current situation, the eventual need for booster vaccines appears likely, though it is unclear if a booster would be required only occasionally, or if it would become a yearly routine. Moderna has already started work on a booster based on the B.1.351 variant, and the Pfizer CEO recently said he expects that boosters will be needed within 12 months of being fully vaccinated. 

In a few years, coronavirus variant boosters may become routine, and eventually the virus may become endemic, and the future global population may merely have to endure a new type of common cold.