Comparing COVID-19 Variants: A Real-World Look at the Effect of Mutations

Background Information for Teachers

As viruses replicate within their host, mutations arise. Every genetic change is a variant of the virus which means that over time viruses have many variants. Not all genetic changes matter though. In terms of a virus's fitness (ability to survive and replicate), mutations fall into three categories.

• Beneficial mutations: these are genetic changes which increase the virus's fitness.
• Harmful mutations: these are genetic changes which decrease the virus's fitness.
• Neutral mutations: these are genetic changes which do not alter the virus's fitness.

Scientists and public health officials are interested in tracking virus variants to determine which, if any, could have beneficial mutations that could have a profound effect on communities. In particular, scientists track whether or not the genetic changes in a variant also change the virus's transmissibility and virulence.

Transmissibility refers to how the virus spreads from person to person and includes information like:

• The latent period of the disease: the average time, usually measured in days, from when a person is infected until they are infectious.
• The infectious period of the disease: the average length of time, usually measured in days, during which an infected individual is infectious.
• The mode of transmission of the disease: diseases can be passed from one person to another in many ways, including through direct contact with bodily fluids like blood, droplet spray from coughing or sneezing, or in the case of airborne diseases, small particles that stay suspended in the air for minutes or hours, even after the infected person has left the area.

In general, mutations which increase a virus's transmissibility are beneficial to the virus and likely to propagate.

Virulence measures the likelihood that infection leads to disease and the severity of the disease, if it occurs. Measures of virulence include information like:

• The chance of being asymptomatic: some people infected with a virus, like COVID-19, are asymptomatic. Asymptomatic patients do not have any disease symptoms, but they can infect others.
• The rate of hospitalization: this is the likelihood that an infected patient will be so ill that they need to be hospitalized.
• The chance of death: this is the likelihood that an infected patient will die of the virus.

Mutations which increase a virus's virulence are bad for the human host, but could be beneficial, harmful, or neutral for the virus. A mutation that causes more symptoms for the host, like an increase in coughing, could be beneficial if it feeds back into the disease's transmissibility. But if the virus becomes so virulent that it kills the host very quickly, this may be a harmful mutation as it may mean that the host does not have enough time to come into contact with other potential hosts and spread the virus. Other mutations could alter the virulence without altering fitness and thus be neutral mutations for the virus.

The original COVID-19 virus quickly caused a pandemic largely because it was novel. Our immune systems had not seen anything like it before so there was no herd immunity nor any vaccines. The original virus was moderately transmissible. A virus's basic reproduction number or R₀ (pronounced R naught) describes its transmissibility. The original COVID-19 virus had an R₀ of 3, which meant that on average every infected individual would infect three more people. Since then, there have been a number of variants of concern (variants where data indicates that there is more virulence and/or more transmission). To date, these variants of concern (like Delta and Omicron) have had beneficial mutations resulting in increased R₀.

Students will learn all of this by using SimPandemic to model what a COVID-19 epidemic looks in a population that has not seen any strain of COVID-19. They will compare the outcomes of an outbreak of each variant and understand how genetic changes can lead to different outcomes for populations.

You will see that students obtain slightly different results, even when they have the same inputs for SimPandemic. Many events in the real world and in a simulation of the real world are based on chance. When you become infected in the real world, you often don't know when or where the infection occurred. Perhaps someone sneezed when you were randomly walking by them. A simulation cannot predict that you were going to get infected (except in special cases), but it can predict fairly well that someone would get infected. In SimPandemic there are many events where the simulation literally rolls virtual dice to determine when an infected individual will transmit the disease to another (all within the bounds specified by the input parameters). To better understand the assumptions and parameters involved, read the SimPandemic FAQ .

Important sidenote: The COVID-19 virus is an RNA virus. This means that it has an RNA genome rather than a DNA genome. Students may not be familiar with RNA genomes. For this reason, the lesson refers to the virus's "genetic material", rather than RNA, as the focus is on the genetic principles being taught and not the similarities and differences of DNA versus RNA genomes.

Additional Background Links

• SARS-CoV-2 Variant Classifications and Definitions, Centers for Disease Control and Prevention

Prep Work (15 minutes)

1. Familiarize yourself with the SimPandemic online software. Read through the SimPandemic FAQ and try out the SimPandemic Notebook associated with this lesson plan.

Engage (15 minutes)

1. Start by describing the following scenario to your students and asking them for their best scientific explanation.

   Imagine this scenario: Public health officials are tracking COVID-19 infections in a community. They take virus samples at random from infected individuals and compare the genomic sequence of the samples to the original COVID-19 virus. A new lab tech has just completed comparing the latest batch of sequences and says to a more experienced lab tech, "Oh no, we're in trouble! The virus has mutated!" The experienced lab tech responds in a calm voice, "Relax, it's probably no big deal."

   Discuss these questions as a class: Why are public health officials sequencing COVID-19 virus samples and comparing them to the original? Whose response do you think is most accurate, the new lab tech's or the experienced lab tech's? Why? Do you need any other information to decide if this mutated virus is a concern? If so, what information?

   Students may be unsure. Encourage them to give their best guesses anyway. Record all answers to revisit at the end of the lesson.

Explore (60 minutes)

1. Tell students that they'll be learning more about virus variants in general and specifically how a few of the COVID-19 variants compare to the original strain of the COVID-19 virus. Distribute a copy of the Student Worksheet to each student. Break the class into pairs if they will be collaborating on the worksheet.
2. See what students already know about this topic.

   Who can tell me what a COVID-19 variant is?

   Students may or may not know what a variant is. Listen to students' answers.

3. Show students the following video to help them understand how viruses replicate, what variants are, and that not all virus mutations matter. Explain that the video was made earlier in the COVID-19 pandemic and while does not discuss the most current variants, the basic science applies to all variants.
   

   https://www.youtube.com/watch?v=RoV-u2mcsZw

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4. Ask students to answer question 1 on their Student Worksheet. Review the correct answer as a class.
5. Set up the next part of the lesson by telling students they will be using an online tool called SimPandemic to learn about COVID-19 virus variants and how they compare to the original COVID-19 strain. Navigate to the SimPandemic Notebook that accompanies this lesson plan and review the graphic in the first section with students. In particular:
   1. Explain to students that this is what a model of the COVID-19 epidemic looks like if no interventions (no masks, no social distancing, no shutdowns, etc.) are used.
   2. Go over the For Simulated Populations of 100,000 outcomes table and how to read the accompanying graph. Make sure every student understands the type of data being presented before continuing.
   3. Emphasize that the outcomes are listed per 100,000 individuals to enable direct comparisons between simulations of different scenarios.
   4. Point out the FAQ button. If students get stuck or have questions about the program, the SimPandemic FAQ is likely to have answers.
   5. Explain that if the simulation was run twenty times, each time the results would be slightly different. This is because the simulation mimics real life in that it looks at the chance of getting infected and the chance of having symptoms or dying. In SimPandemic there are many events where the code underlying the simulation literally rolls virtual dice to determine when an infected simulant will transmit the disease to another person (all within the bounds specified by the input parameters). Just like rolling dice in a board game, the results can vary within a predictable statistical range.
6. Direct students to work independently, or in pairs, to read through the information in sections 1 and 2 of the SimPandemic Notebook and answer the questions 2-6 in the Student Worksheet. [Tip: Students will need to draw on information in the SimPandemic Notebook and from the video they saw in class to answer the questions. It may be useful for students to be able to re-watch the video.]
7. Review the answers to questions 2-6 as a class to make sure that all students have understood the material.
8. Set up the next part of the lesson by having a student read out loud section 3 of the SimPandemic Notebook. Poll your students about their hypotheses.

   What is your hypothesis? Will the epidemic progress differently if we run simulations with different COVID-19 variants? How do you think it will change? How do you think it will stay the same?

9. Tell students that they will have the opportunity to test their predictions by exploring and running their own simulations. They will use the buttons at the bottom of the Sandbox to run simulations for several COVID-19 variants. They should fill out the data tables in their Student Worksheet and use the data they gather to answer questions 7-10.
10. When all students are done, review the answers for questions 7-10 to make sure that all students have understood the material.

Reflect (15 minutes)

1. Consider whether you want to assess the students' knowledge prior to this part of the lesson.
2. Remind students of the scenario you laid out for them at the beginning of this lesson about one lab technician finding a virus mutation and being concerned, while the other lab technician was not concerned (see the Engage section for details). Read back the associated questions and the answers the class originally came up with. Ask students how they would answer those questions now.

   Why are public health officials sequencing COVID-19 virus samples and comparing them to the original?

   Whose response do you think is most accurate, the new lab tech's or the experienced lab tech's? Why?

   Do you need any other information to decide if this mutated virus is a concern? If so, what information?

   Answers are available in the Student Assessment Answer Key.

Assess

Prior to reflecting on the original scenario as a class, ask students to write their own answers out using the Student Assessment (PDF). Collect these for grading before discussing as a class.

Make Career Connections

Discussing or reading about these careers can help students make important connections between the in-class lesson and STEM job opportunities in the real world.

Epidemiologist

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Career Profile

Epidemiologists work to study, understand, and contain outbreaks. They often work in public health roles to help devise and implement procedures, like vaccination campaigns, that prevent outbreaks. When an outbreak occurs, they are on the front lines, dealing with the outbreak and communicating life-saving information to the public, as well as uncovering important information like how infectious a virus is and how it is changing over time. Read more

Physician

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Career Profile

Physicians are often the first to recognize an uptick in local cases of a disease, or the emergence of a new disease. They play a big role in sounding the alarm at the beginning of an outbreak, in addition to treating infected patients. Read more

Biological Technician

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Career Profile

Technicians process all the virus samples for sequencing as well as any other testing public health laboratories might be doing during an outbreak. They play a critical role in generating the information that epidemiologists and other researchers need to evaluate variants and may even do part of the initial analysis of the sequences to understand how the virus is evolving. Read more

Lesson Plan Variations

• Explore the other SimPandemic Notebooks and their accompanying lesson plans.
• Have students enter their own values into SimPandemic to explore how adding mitigation factors (like masking or quarantining) and vaccines change the course of the COVID-19 epidemic. This can be done with the original COVID-19 virus or any of the variants.
• Have students invent their own COVID-19 variants. They should describe the characteristic(s) unique to their variant, explain how those changes would be beneficial, harmful, or neutral to the virus, predict how the characteristics would alter the course of a COVID-19 epidemic, and test their predictions using SimPandemic.