It has been one year since the WHO declared COVID-19 a pandemic. As countries race to vaccinate people as quickly as possible, the virus continues to rapidly spread. While many SARS-CoV-2 variants have been identified, few were of concern until September 2020, when the first variant to make headlines emerged in the U.K. In this article, we discuss which variants cause concern, and what that can mean for manufacturers of treatments and vaccines, and for the general public.

All viruses contain genetic material, either DNA or RNA, and reproduce by infecting host cells and hijacking their cellular machinery to replicate. Coronaviruses are characterized by the presence of spike proteins protruding from their surface, which bind to receptors of a host cell in order to invade it. With SARS-CoV-2, the spike protein binds to the human ACE2 receptor. After binding to the receptor, the virus enters the cell, makes multiple copies of itself, and releases new virus particles into the blood which transports the virus throughout the body. During this replication process, mistakes can be made when copying the genetic material, although most of these mutations are inconsequential or can even harm the virus.


Occasionally, the buildup of changes, additions or deletions in the genetic code can cause substantive changes to the virus. Specifically, mutations in the portion of the RNA that encodes the virus’s spike protein are most likely to significantly impact the virus’s ability to enter human cells or render a person’s antibodies less effective at preventing infection. While different SARS-CoV-2 variants contain distinct sets of mutations, all are considered part of the same SARS-CoV-2 strain.


As a virus class, coronaviruses tend to mutate relatively slowly compared to other RNA viruses. On average, a typical SARS-CoV-2 virus, which has about 30,000 nucleotides encoding at least 29 genes, may accumulate two mutations per month. In comparison, influenza and HIV pick up mutations much quicker, with the latter having a rate of change up to four times that of SARS-CoV-2. Nonetheless, as infection rates rise, so do opportunities for mutation, increasing the likelihood that variants of concern will arise. 

Although the scientific community has identified many SARS-CoV-2 variants with different mutations, variants are of particular concern if they exhibit any of the following characteristics:

  • Higher transmissibility: Increased rate of infection from person-to-person
  • Increased virulence: Increased disease severity or mortality
  • Reduced detectability: Less detectable through current tests, which were developed to detect the SARS-CoV-2 sequence isolated early in 2020
  • Reduced prevention/treatability: Decreases effectiveness of available vaccines or treatments

At the time of writing, at least five SARS-CoV-2 variants have been identified as potentially concerning, given evidence of one or more of these characteristics.

The B.1.1.7. variant emerged in the U.K. around September 2020 and is believed to be about 50 percent more transmissible than the original wild type virus. About a month later, the B.1.351 variant was identified in South Africa and draws concern primarily due to the potential for immune escape. This happens when mutations alter the virus to the point where it can no longer be recognized by antibodies and survives the immune responseallowing the virus to escape and replicate. In January 2021, P.1 was identified in individuals traveling from Brazil to Japan and is believed to have a similar profile to B.1.351.


Historically, the rise of concerning variants for viral endemics depended heavily on both the class of the virus and the prevalence of the disease. SARS-CoV-1, which led to the 2002 SARS epidemic, was similarly considered a relatively stable viral strain. Like SARS-CoV-2, SARS-CoV-1 had a proofreading mechanism that minimized errors during the replication process. But unlike today’s virus, no SARS-CoV-1 variants affecting transmissibility, severity, detectability or treatability were identified as the virus infected only about eight thousand people. This is just a tiny fraction of the 112 million affected by the COVID-19 pandemic. While today’s virus is similarly a slowly mutating strain, widespread transmission has enabled an increasing number of concerning variants to arise.


Conversely, the 1918 influenza pandemic led to about 500 million infections globally, spreading in three waves during the spring and fall of 1918, and spring of 1919. While the mortality of the first wave was likened to the seasonal flu, the mortality of the second wave soared. Historians now believe the second wave resulted from a variant spread during wartime troop movements. The 1918 influenza illustrates the potential danger of a highly infectious virus that spreads rapidly. While the virus initially caused relatively low disease severity, the rapid spread of a fatal variant led to an estimated 50 million deaths.

Most COVID-19 vaccines and therapies were developed based on the original wild type virus sequenced in January 2020. Major changes in the genetic sequence of the virus could potentially render products to be less effective, or even completely ineffective.


Current COVID-19 vaccines authorized for emergency use train the immune system to recognize the spike protein isolated from the original wild type virus genome sequenced in early 2020. The immune system produces antibodies and activates other immune cells to fight off what is recognized as foreign, protecting against future infections from SARS-CoV-2. As the immune response elicited by the vaccine creates antibodies against several targets on the spike protein, evidence suggests current vaccines offer protection against COVID-19, albeit with observed reductions in efficacy in the face of select emerging variants of concern, particularly B.1.351. 

Conversely, monoclonal antibodies (mAbs) are laboratory-engineered antibodies that bind to a single specific target on the SARS-CoV-2 virus spike protein and can neutralize the virus. However, if the target is altered by mutations, this may result in dramatically reduced or completely eliminated neutralizing activity. As a result, several mAb manufacturers are investigating antibody cocktails that combine two or more antibodies, which may increase the potential for efficacy against current and future variants. For example, Eli Lilly’s neutralizing antibody Bamlanivimab (LY-CoV555), which had previously been authorized for emergency use, is reported to be inactive against the B.1.351 variant and standalone usage has now halted. The company has now partnered with GSK/Vir to evaluate combination treatments in COVID-19 patients to tackle new variants.  


Continued assessment of emerging variants and their impact to vaccine and treatment efficacy remains critical, as clinical development will need to evolve rapidly to combat ongoing mutations. Some manufacturers are opting to design booster vaccines against variants that cause reduced vaccine efficacy. For example, Pfizer recently announced the initiation of a study to assess the safety and immunogenicity of a third dose of its vaccine against emerging variants. Additionally, Moderna also plans to evaluate three approaches to boosters, including a variant-specific candidate and a multivalent candidate, that is a vaccine targeting multiple variants, as well as a third dose booster candidate.


However, designing additional booster shots may reduce the potential interchangeability between the vaccines. Booster doses of vaccines are normally administered as a series of shots from the same vaccine manufacturer. If new boosters target new variants, then manufacturers will likely first demonstrate efficacy in patients that received the first doses of their vaccine addressing the original wild type virus. Additionally, once an individual takes the first two doses of one vaccine, healthcare providers may feel more comfortable recommending additional booster shots from the same manufacturer, unless the manufacturers demonstrate booster doses are effective after a priming regimen from their competitors. Crossover studies analyzing the effect of mixing vaccines are already underway. Researchers in the U.K. launched a mixed vaccine trial to test participants’ immune responses to receiving one shot of the AstraZeneca vaccine and another from Pfizer-BioNTech. Others are evaluating combinations of Russia’s Sputnik V with AstraZeneca’s COVID-19 vaccine. Single dose vaccines may help establish widespread immunity faster if they prove efficacious against multiple variants. 

To date, evidence suggests that all vaccines authorized for emergency use prevent hospitalizations and death across the currently circulating variants, though overall efficacy may vary. In the long-term, the industry may consider an investment in research for universal SARS-CoV-2 products, similar to current efforts to develop a universal influenza vaccine. Researchers have already begun developing prototypes of a pancoronavirus vaccine, which yielded promising early results in animal models. Other scientists are racing to explore nanoparticle technology that generates antibodies for multiple coronaviruses, as well as other forms of a universal coronavirus vaccine that do not rely on antibodies that bind to the spike protein, but instead target another surface protein. Current efforts to develop testing capabilities, treatments and vaccines targeting all variants of SARS-CoV-2 could preclude the need to initiate separate trials for efficacy against each variant or for each new booster. In the meantime, experts are hopeful that new boosters in development for currently authorized vaccines will rapidly become available to address variants in circulation.