Teacher Notes for “Coronaviruses – What They Are and How They Can Make You Sick”1

This analysis and discussion activity introduces students to the novel coronavirus and the disease it causes. Students learn how coronaviruses are replicated, analyze how the respiratory and circulatory systems work together to provide oxygen to the body’s cells, and learn about the immune responses to coronavirus infection. This provides the basis for students to understand how a coronavirus infection can cause mild temporary illness or serious and even fatal illness.

NGSS Learning GoalsIn accord with the Next Generation Science Standards (NGSS)2: This activity helps students to prepare for Performance Expectation HS-LS1-2. “Develop and

use a model to illustrate the hierarchical organization of interacting systems that provide specific functions within multicellular organisms.”

This activity helps students to understand the Disciplinary Core Idea LS1.A. “Multicellular organisms have a hierarchical structural organization, in which anyone system is made up of numerous parts and is itself a component of the next level.”

Students engage in the Scientific Practice, “Constructing Explanations. Apply scientific ideas, principles and/or evidence to provide an explanation of phenomena…”

This activity helps students to understand the Crosscutting Concept, “Cause and Effect: Mechanism and Prediction. Cause and effect relationships can be suggested and predicted for complex natural… systems by examining what is known about smaller scale mechanisms within the system.”

Instructional Suggestions and Biology BackgroundIt will be helpful if students have a basic understanding of proteins, RNA, ribosomes, cells, organs, and organ systems before they begin the activity.

If your students are learning online, we recommend that they use the Google Doc version of the Student Handout available at https://serendipstudio.org/exchange/bioactivities/coronavirusprev. To answer questions 2, 4 and 8, students can either print the relevant pages, draw on those and send you pictures, or they will need to know how to modify a drawing online. They can double-click on the relevant drawing in the Google Doc, which will open a drawing window. Then, they can use the editing tools to add lines, shapes, and text boxes.3 If you are using the Word version of the Student Handout to make revisions, please check the PDF version to make sure that all figures and formatting are displayed properly in the Word version on your computer.1 By Dr. Ingrid Waldron, Department of Biology, University of Pennsylvania, 2020. These Teacher Notes and the related Student Handout are available at https://serendipstudio.org/exchange/bioactivities/coronavirusintro . 2 Quotations are from http://www.nextgenscience.org/sites/default/files/HS%20LS%20topics%20combined%206.13.13.pdf 3To draw a line

1. At the top of the page, find Select line and pick the type of line you want.2. Place the line on your drawing:

Line, Elbow Connector, Curved Connector or Arrow: Click to start, then drag across the canvas. Curve or Polyline: Click to start, then click at each point you want the line to bend. Double-click or complete

the shape to finish. Scribble: Click to start, then drag across the canvas.

To draw a shape1. At the top of the page, find and click Shape.2. Choose the shape you want to use.3. Click and drag on the canvas to draw your shape.

To insert text1. At the top of the page, click Insert.

To place text inside a box or confined area, click Text Box and drag it to where you want it.2. Type your text.3. You can select, resize and format the word art or text box, or apply styles like bold or italics to the text.

When you are done, click Save and Close.1

A key is available upon request to Ingrid Waldron (iwaldron@upenn.edu). The following paragraphs provide additional instructional suggestions and background information – some for inclusion in your class discussions and some to provide you with relevant background that may be useful for your understanding and/or for responding to student questions.

To maximize student participation and learning, I suggest that you have your students work individually or in pairs to complete each group of related questions and then have a class discussion after each group of questions. In each discussion, you can probe student thinking and help them develop a sound understanding of the concepts and information covered before moving on to the next group of related questions.

A class discussion of student answers to question 1 will help you to understand your students’ current knowledge, including any misconceptions they may have. You may want to mention famous people who have had coronavirus infection (particularly younger adults; https://www.nytimes.com/2020/05/29/sports/coronavirus-survivors-athletes.html; https://www.wonderwall.com/celebrity/photos/famous-people-who-have-tested-positive-coronavirus-covid-19-3022493.gallery; https://www.today.com/health/pink-details-her-her-son-s-terrifying-coronavirus-battles-t178058).

Introduction to CoronavirusThe novel coronavirus that is causing the current global pandemic is called SARS-Cov-2 because of its similarity to SARS-Cov, a coronavirus that caused an epidemic of Severe Acute Respiratory Syndrome in 2002-2004, mainly in Asia. The disease caused by SARS-Cov-2 is called COVID-19. CO stands for corona, VI stands for virus and D stands for disease; 19 stands for 2019, the year in which this disease was first identified. As of September 30, the estimated number of COVID-19 deaths was 206,000 in the US and 1.01 million in the world (https://www.google.com/search?q=Estimated+deaths+worldwide+Covid+19&rlz=1C1GCEA_enUS862US862&oq=Estimated+deaths+worldwide+Covid+19&aqs=chrome..69i5

7.4118j0j7&sourceid=chrome&ie=UTF-8).

This three-dimensional view of a coronavirus may be helpful for some students.4 In addition to the proteins and RNA mentioned on page 1 of the Student Handout, the coronavirus has an envelope (similar to a cell membrane). The diameter of a coronavirus is roughly 100 nm, whereas the diameter of a human epithelial cell is roughly 50 µm or roughly 500 times bigger. As briefly mentioned in the recommended video, most biologists consider viruses to be intermediate between living organisms and things that are not alive. Viruses cannot reproduce or use energy on their own, but they do evolve (which is almost certainly how this new coronavirus originated; see “Where did the new coronavirus come from?”, https://serendipstudio.org/exchange/bioactivities/coronavirusOrigin). Students should be aware of the difference between

4 This figure is from https://callisto.ggsrv.com/imgsrv/FastFetch/UBER1/ZI-1300-2003-MAY30-IDSI-4-1.2

viruses and bacteria. Bacteria are prokaryotic cells which can reproduce and use energy. Antibiotics can kill bacteria, but not viruses.

Page 1 of the Student Handout recommends the video, “What actually happens if you get coronavirus?” (https://www.youtube.com/watch?v=OTYfke545vI). This video provides a good introduction, but the second half contains some inaccuracies because it was made early in the pandemic and we have learned a lot since that time. Obviously, the number of deaths has increased exponentially since then. At about 4 minutes, the narrator refers to the Wuhan virus, which properly should be called the SARS-Cov-2 virus. The part of the video after 4 minutes and 45 seconds is not recommended because recent research has revealed that several points included in this section are not accurate. The narrator says that the main defense is antibodies, but T cells appear to be at least as important. Pages 4-7 of these Teacher Notes provide a more up-to-date description of the pathophysiology of COVID-19.

This video (2 minutes to 3 minutes and 30 seconds) provides a concise, accurate description of coronavirus replication. The coronavirus spike protein binds to a receptor on the surface of cells in the nose, lungs and multiple other parts of the body. This binding causes the viral envelope to merge with the cell membrane, and this allows the viral RNA to enter the cell (illustrated in https://www.scientificamerican.com/interactive/inside-the-coronavirus/). Coronavirus RNA serves as mRNA. The cell’s ribosomes translate viral mRNA to make viral proteins. The viral RNA is copied by a viral enzyme, RNA-dependent RNA polymerase (replicase in the figure below). One of the approved treatments for coronavirus infection is Remdesivir, which interferes with this enzyme. The membrane that will become the viral envelope is derived from the Golgi apparatus. The viral envelope, proteins and RNA assemble to form multiple new viruses that are released from the infected cell, which typically dies. The released viruses can infect other body cells, can be inactivated by the immune system, or can be spread to infect other people by coughing, sneezing, shouting, singing, or breathing.

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(https://www.nature.com/articles/nrmicro2090?proof=trueJul; to be completely accurate, this figure should show each ACE2 molecule on the surface of the human cell binding to a single coronavirus spike protein.)

How can something so tiny make a person so sick?This section of the activity provides a good opportunity to review levels of organization in biology with your students. For example, the figure on the top of page 2 of the Student Handout can be used to review the importance of understanding biological structure and function at the levels of molecule, cell, organ and organ system. Question 5 will reinforce student understanding that interacting organ systems are needed to accomplish functions such as supplying all the body’s cells with oxygen.

To help your students understand the structure and function of the lungs and how pneumonia can develop, you may want to show them the section beginning at 2 minutes and 43 seconds and ending at 5 minutes from the video, “What Happens If You Get Coronavirus” (https://www.youtube.com/watch?v=5DGwOJXSxqg). This section of the video includes an explanation of how the lungs help to rid the body of carbon dioxide, a point which is not

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included in the Student Handout. (In the earlier part of this video, the description and image of the proteins protecting the RNA is inaccurate.)

Coronavirus infection may result in no noticeable symptoms, a few nonspecific symptoms (e.g. fever), or severe infection and even death. Scientists do not yet know why coronavirus infection results in different symptoms and different severity in different people, although they do know some factors that contribute. Immunocompromised individuals and elderly people have a much greater risk of severe infections and death. (Elderly people have decreased immune function.) Another possibility is that a person who has inhaled more coronaviruses may tend to develop a more severe case of COVID-19. It is believed that a minimum dose of a few hundred or several thousand viruses is needed to start an infection (https://www.ashclinicalnews.org/online-exclusives/much-coronavirus-must-present-get-sick/).5

The figure below summarizes scientists’ understanding of how the coronavirus can affect multiple parts of the body (as of April, 2020). Notice that the coronavirus appears to move from the alveoli to infect capillary cells and spread to other organs in the body. You and/or your students may want to explore “Could my symptoms be COVID-19?” (https://www.nytimes.com/interactive/2020/08/05/well/covid-19-symptoms.html) or “Organ-by-organ, see how the coronavirus can attack the body” (https://www.inquirer.com/health/coronavirus/inq/coronavirus-symptoms-affects-organs-human-body-20200821.html).

(https://science.sciencemag.org/content/sci/368/6489/356/F1.large.jpg)

5 People who have heart disease, diabetes or obesity are also more likely to develop a severe coronavirus infection (https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/evidence-table.html).

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The figure below shows a more detailed view of the effects of a severe coronavirus infection on an alveolus. “Pulmonary edema” shows the fluid that accumulates in the alveoli. The “hyaline membrane” includes molecular debris and dead cells. Both pulmonary edema and the hyaline membrane interfere with diffusion of oxygen from the air in the alveolus to the blood in the capillaries. The “pulmonary thrombus” represents the growing awareness that blood clots that block or reduce the circulation of blood contribute significantly to the pathophysiology of coronavirus infections (https://elemental.medium.com/coronavirus-may-be-a-blood-vessel-disease-which-explains-everything-2c4032481ab2). The importance of blood clots is reinforced by the finding that treatment with anticoagulant drugs significantly increased survival of hospitalized COVID-19 patients (https://www.medscape.com/viewarticle/936601?nlid=137129_5402&src=wnl_dne_200901_mscpedit&uac=49468FT&impID=2539459&faf=1).

(https://jamanetwork.com/journals/jama/fullarticle/2768391)

The immune system can have both beneficial and harmful effects in coronavirus infection. As described in the Student Handout, immune defenses are often sufficient to rid the body of coronavirus with only mild symptoms or none. However, the novel coronavirus has one or more genes that allow it to block a helpful early immune response (interferons). Also, later in a severe coronavirus infection, the immune system often stimulates a harmful over-response that damages multiple organs in the body (called sepsis). This harmful over-response is triggered by a “cytokine storm”, which is the overproduction of chemical messengers that stimulate excessive immune system activity. Dexamethasone (a corticosteroid) can reduce these harmful immune responses and has been shown to significantly increase survival in critically ill COVID-19 patients (https://www.medscape.com/viewarticle/936813). However, dexamethasone can also inhibit helpful immune responses, so it should only be given to appropriate patients.

If you want your students to understand the function of the immune system, I recommend an 8-minute video, “Why fully recovering from the coronavirus might take longer than expected” (https://www.wsj.com/articles/covid-long-term-effects-sports-athletes-nba-bubble-11593161922). For a more complete description of the immune responses to coronavirus infection, I recommend “Immunology Is Where Intuition Goes to Die” (https://www.theatlantic.com/health/archive/2020/08/covid-19-immunity-is-the-pandemics-

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central-mystery/614956/). This article includes the following quote as part of its discussion of the widespread failure to understand how complex the immune system is.

“Even the word immunity creates confusion. When immunologists use it, they simply mean that the immune system has responded to a pathogen—for example, by producing antibodies or mustering defensive cells. When everyone else uses the term, they mean (and hope) that they are protected from infection—that they are immune. But, annoyingly, an immune response doesn’t necessarily provide immunity in this colloquial sense. It all depends on how effective, numerous, and durable those antibodies and cells are.”

To answer question 9, students should integrate and organize relevant information presented in the Student Handout. After your students complete their flowcharts, I suggest that you give them prompt feedback so they can improve the accuracy and completeness of their answers. One way to accomplish this is to have pairs of students collaborate to answer question 9; then you can display several of their flowcharts for the student creators to explain and the class to discuss.6 This type of active recall with feedback helps to consolidate student understanding and retention of the concepts learned during the activity.7

You may want to relate the steps in student flowcharts to current treatments for severe coronavirus infections (https://www.covid19treatmentguidelines.nih.gov/). These Teacher Notes have already discussed Remdesivir (page 3) and dexamethasone (page 6). Air is only 21% oxygen, so patients who are having trouble breathing can be helped by adding oxygen to the air they inhale. A ventilator can help when a patient becomes so sick that he/she has trouble breathing.

Follow-Up Activities Changing Recommendations about How to Reduce Your Risk of Coronavirus Infection – What is the evidence?https://serendipstudio.org/exchange/bioactivities/coronavirusprevIn this analysis and discussion activity, students learn about the scientific basis of recommendations to reduce the spread of coronavirus infections. They analyze how changes in the recommendations resulted from new research findings about the behaviors and situations that increase or decrease the risk of coronavirus infection.

Where did the new coronavirus come from?https://serendipstudio.org/exchange/bioactivities/coronavirusOrigin

6 If your class is meeting in person, you can have small groups of students collaborate to draw their flowcharts on whiteboards. For information about how to make inexpensive whiteboards and use them in your teaching, see "The $2 interactive whiteboard" and "Resources for whiteboarding" in https://fnoschese.wordpress.com/2010/08/06/the-2-interactive-whiteboard/. You can go to Home Depot and ask them to cut a 8' x 4' whiteboard (e.g. EUCATILE Hardboard Thrifty White Tile Board) into six pieces with the dimension 32" x 24". They should have a power saw rig that allows their employees to cut the pieces very easily. They should not charge to cut them and the product cost is reasonable. Some additional tips are:– Coat the white boards with Endust (or similar product) before using. Every once in a while wipe them clean and reapply Endust.– Do not use markers that are old or almost empty. The ink from these are more difficult to erase.– Black markers erase easiest.– Best if boards are erased immediately after use.– Teacher and/or students can take a picture of the information on the board if they want to save it.7 Evidence for the benefits of active recall with prompt feedback is described in http://www.scientificamerican.com/article/researchers-find-that-frequent-tests-can-boost-learning/.

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In this analysis and discussion activity, students explore the main hypotheses about the origins of the new coronavirus that is causing the current pandemic. Students learn how mutations, natural selection, and contact between species can work together to produce a spillover infection. They analyze how a previous coronavirus spillover infection caused an earlier outbreak of human infectious disease. Molecular evidence is presented for students to evaluate the hypothesis that genetic engineering produced the new coronavirus. In addition, students explore possible strategies for preventing new spillover infections.

How Genes Can Cause Disease – Understanding Transcription and Translationhttps://serendipstudio.org/exchange/bioactivities#molecbioAfter students learn about the processes of transcription and translation, students use their understanding of translation to develop a partial explanation of how the coronavirus replicates inside our cells.

COVID-19 Curriculum Materialshttps://epiclearning.web.unc.edu/covid/In the most relevant of the three activities, students use a mathematical model, programmed within a spreadsheet (Google Sheets), to explore viral transmission and exponential growth. It enables comparisons of viruses with different reproduction numbers (R0) numerically and graphically. This activity challenges students to think through various implications of the model and to consider strategies for reducing R0 for a virus and the associated impacts and viral transmission. Another suggested activity is designed to improve media literacy.

If your students have additional questions about the novel coronavirus and the COVID-19 pandemic, you may want to encourage them to research these questions using the following sources of reliable information.

the Sources of Information section of Resources for Teaching about Coronavirus (https://serendipstudio.org/exchange/bioactivities/coronavirus)

the CDC website (https://www.cdc.gov/coronavirus/2019-ncov/index.html), Science (https://www.sciencenews.org/editors-picks/2019-novel-coronavirus-outbreak) New York Times (https://www.nytimes.com/news-event/coronavirus).

Sources for Student Handout Figures Figure of coronavirus structure, adapted from

https://web.mit.edu/fnl/volume/324/king_etal.html Figure of respiratory system and alveolus, adapted from https://teachmeanatomy.info/wp-

content/uploads/The-Bronchial-Tree.jpg and https://images.slideplayer.com/15/4628344/slides/slide_23.jpg

Figure of circulatory system, adapted from https://s4.thingpic.com/images/85/zNiMHr2r5NxXEiuCcWJ5avYp.png

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