Merck Manual

Please confirm that you are not located inside the Russian Federation

honeypot link

Commentary: Coronavirus Variants and the COVID-19 Pandemic

06/29/2021 Matthew E. Levison, MD, Drexel University College of Medicine|Drexel University;

When a virus replicates, mistakes, called mutations, sometimes occur in the sequence of nucleotides (the building blocks of genes). Mutations occur by chance, so the more viruses that are replicating, the higher the chance of a mutation. Many of the mutations are inconsequentialthey neither help nor hurt the virus; some mutations weaken the virus; but a very few mutations give the virus a survival advantage, such as by enhancing transmission. Mutants with a survival advantage eventually become the dominant version of the virus. Over time, a virus accumulates multiple mutations. A group of viruses that share the same inherited set of distinctive mutations is called a variant.


Variants of SARS-CoV-2, the coronavirus that causes COVID-19, have been given different names by various organizations, but the World Health Organization (WHO) has recently resolved this problem by naming variants with letters of the Greek alphabet. The alpha variant was first detected in the UK. The beta variant was first detected in South Africa. Gamma was first detected in Brazil, delta was first detected in India, and epsilon was first detected in California in the United States (1).


Variants of concern (VOC) are those variants that have public health consequences, typically because they have one or more of the following properties:

  • More transmissible
  • Cause more severe disease
  • Not as easily neutralized by antibodies (including natural antibodies generated in the body by previous infection or vaccination, and monoclonal antibodies created in a lab to use for treatment)
  • Not as easily detected by diagnostic tests, such as a PCR (polymerase chain reaction) test (2)

The alpha, beta, gamma, delta, and epsilon variants have been designated as VOC in the United States (1).


Many VOCs involve one or more mutations in the SARS-CoV-2 's spike protein. Spike protein mutations can be of concern because the spike protein is the part of the virus that interacts with receptors on the surface of the host cell, allowing the virus to bind to and then enter the host cell. Parts of the spike protein are also common targets of antibodies produced by the body’s immune system to defend against the virus. That means that mutations that affect the spike protein could make it easier for the virus to attack a host cell and/or harder for the immune system to attack the virus. This could increase virus infectivity, and possibly disease severity. Although it is not yet known how many particles of SARS-CoV-2 have to be inhaled to cause infection, that number would likely be lower for a virus that is better at binding to the spike protein. Furthermore, because the genes that encode the spike protein also are one of the main SARS-CoV-2 viral components looked for by common diagnostic viral tests (such as PCR tests), mutations in the spike protein may make it harder for certain tests to identify the virus.


Because of their increased transmissibility, the alpha, beta, gamma, and delta variants have spread worldwide (3).


Alpha Variant


The alpha variant was first detected in Kent, a county in South East England, and in London in September 2020 (4). Over the next several months, this variant, which was transmitted faster than other variants circulating at the time, rapidly became dominant in the UK (only to be later overtaken by the even more transmissible delta variant). The alpha variant arrived in the United States late in November 2020. By January 2021, it had spread to at least 30 U.S. states and became the dominant variant in many U.S. states by March 2021 (5). On May 8, the alpha variant peaked at about 70% of new infections in the U. S. and now accounts for about 52% of new infections as it is being replaced by the delta variant (6).


In the UK, the alpha variant is thought to be associated with an increased risk of death (7), but more studies are needed to confirm this. Some versions of the alpha variant are also better at evading the body’s immune system than other alpha variants (8).


Two doses of the Pfizer-BioNTech vaccine are about 90% effective in preventing any infection with the alpha variant and over 97% effective at preventing severe, critical, or fatal disease (9).


Beta, Gamma, and Epsilon Variants


The beta variant was first detected in South Africa in December 2020 and remains dominant there. This variant was first detected in the U. S. at the end of January 2021, but currently accounts for less than 1% of infections in the U.S. In Qatar, 2 doses of the Pfizer-BioNTech vaccine were about 75% effective at preventing any infection with the beta variant, and over 97% effective at preventing severe, critical, or fatal disease.


The epsilon variants were first identified in California in February 2021. There are 2 main epsilon variants and they currently account for less than 1% of infections in the U.S. (6).


The gamma variant was first detected in travelers from Brazil, who were tested during routine screening at an airport in Japan, in early January 2021. This variant is dominant in Brazil and is spreading throughout South America (10). As of mid-June 2021, it accounted for over 16% of infections in the U.S., having almost doubled during the previous month (6). This emerging variant must be watched closely.


Delta Variant


The delta variant, which is dominant in India, has about a 40% higher transmission rate than the alpha variant, which itself is 50% more transmissible than the original strain of the virus. In the UK, the delta variant has now displaced other variants and currently accounts for 96% of all new cases.


Symptoms of infection with the delta variant differ from those of the original virus strain. Headache, sore throat, and a runny nose are common, rather than the classic symptoms of COVID-19 (such as cough, fever, and loss of smell or taste).


The delta variant is more likely to lead to hospitalizations than the alpha variant, despite spreading primarily among younger people. In England, the delta variant is spreading mostly in unvaccinated groups, but about 6% of new cases were in fully vaccinated people and 26% of new cases occurred in people who had received 1 dose of vaccine (11). The delta variant also appears to be dangerous. In England, a study looked at 42 deaths in people with the delta variant and found that 23 of those were unvaccinated, 7 had received only one dose of vaccine, and 12 had been fully vaccinated . Because of the spread of the delta variant, England’s planned removal of all remaining public-health restrictions on June 21, 2021, has been delayed.


The situation in the UK may portend what will happen in the United States as the delta variant replaces the alpha variant as a cause of new cases; the delta variant went from 0.1% of new cases in early April 2021 to 10% of new cases on June 5, 2021, and over 20% on June 19 (6).


Nevertheless, there is evidence that 2 doses of the Pfizer-BioNTech and AstraZeneca vaccines retain similar effectiveness against the delta variant as against the alpha variant. In a recent press release, Public Health England said that 2 doses of the Pfizer-BioNTech vaccine are 96% effective in preventing hospitalization and 88% effective in preventing symptomatic disease, and 2 doses of the AstraZeneca vaccine are 92% effective in preventing hospitalization and 67% effective in preventing symptomatic disease (12).


Although the full vaccine regimens appear to provide excellent protection against the delta variant, one dose of these 2-dose vaccines gives only limited protection — one dose of either the Pfizer-BioNTech or the AztraZeneca vaccine was just 33% effective against symptomatic disease caused by the delta variant compared with about 50% effectiveness against the alpha variant. This finding prompted the governments of the UK and France to reduce the period between the 2 doses.


A recent study analyzed antibody levels in the blood of 250 healthy people up to 3 months after the first of either one or two doses of the Pfizer-BioNTech Covid-19 vaccine (13). People fully vaccinated with 2 doses of the vaccine had levels of neutralizing antibodies that were more than 5 times lower against the delta variant when compared to the original strain. The antibody response was even lower in people who had only received one dose. Levels of neutralizing antibodies are lower with increasing age, and levels decline over time, suggesting a booster dose may be needed in vulnerable people. In addition, partial vaccination may enable the emergence of new variants that more easily escape immune control.



Prevention of COVID-19 becomes particularly important at this time because more highly transmissible variants are emerging. The more a virus circulates in the human population, the more opportunities it has to mutate. Slowing transmission slows the emergence of mutations. However, nonpharmaceutical interventions to reduce transmission, including wearing masks, physical distancing, improving indoor ventilation, avoiding crowded places, and restricting travel are being rolled back in many locations, increasing the risk of transmission. Also, there are no antiviral drugs currently available that can be easily taken to prevent or treat early SARS-CoV-2 infection. 


Nevertheless, we are extremely fortunate to have several vaccines that are about 90% effective at preventing symptomatic infection and even more effective at preventing hospitalizations and death from COVID-19 caused by the more easily transmissible and virulent SARS-CoV-2 variants, but only when fully vaccinated with 2 doses. Partial vaccination with one dose of these vaccines has not been shown to be effective and may be deleterious. Even after 2 doses with these vaccines, a booster dose may subsequently be required as neutralizing antibody levels wane over time. The SARS-CoV-2 variants are dangerous, but manageable by fully vaccinating populations everywhere as quickly as possible.




1. Centers for Disease Control and Prevention: SARS-CoV-2 variants classifications and definitions. June 23, 2021.

2. World Health Organization (WHO): Tracking SARS-CoV-2 variants. May 31, 2021.

3. Centers for Disease Control and Prevention: COVID data tracker: Global variants report. Accessed June 23, 2021.

4. Rambaut A, Loman N, Pybus O, et al: Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. December 9, 2020.

5. Washington NL, Gangavarapu K, Zeller M, et al: Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States. [PREPRINT] MedRxiv February 7, 2021

6. Centers for Disease Control and Prevention: COVID data tracker. Variant proportions. Accessed June 23, 2021.

7. Iacobucci G: Covid-19: New UK variant may be linked to increased death rate, early data indicate, BMJ 372:n230, 2021 doi:10.1136/bmj.n230.

8. Wise J: Covid-19: The E484K mutation and the risks it poses. BMJ 372:n359, 2021. Doi:10.1136/bmj.n359. https//

9. Abu-Raddad LJ, Chemaitelly H Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med May 5: NEJMc2104974, 2021.

10. Taylor L: Covid-19: How the Brazil variant took hold of south America. BMJ 373:n1227, 2021.

11. Davis N: Delta variant causes more than 90% of new Covid cases in UK. The Guardian June 11, 2021.

12. Public Health England: Vaccines highly effective against hospitalisation from delta variant. [press release] June 14, 2021

13. Haas EJ, Angulo FJ, McLaughlin JM, et al: Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: An observational study using national surveillance data. Lancet 397: P1819-P1829, 2021.
Matthew Levison, MD

Test your knowledge

Motion Sickness
Motion sickness includes symptoms, particularly nausea, that affect people while they ride in a moving object. The object can be a transport vehicle such as a car, boat, train, or airplane, or an amusement park ride. A contributing factor is over-stimulation of a part of the body involved in balance control. Which of the following is that body part?