The Coronavirus Pandemic – Answering Your Questions
Students may have questions related to the coronavirus pandemic or you may be teaching about it. This page provides information about some of the questions that have been pressing during the course of the pandemic. If you would like to see other questions addressed, you can email questions to email@example.com. We also have a dedicated page on the VEC website. Go to COVIDVaccineAnswers.org for even more information.
What are the side effects of the COVID-19 mRNA vaccines?
- Side effect: An effect that occurs after receipt of a medication or vaccine. Even though these are unwanted, they can be expected based on previous experience (e.g., clinical trials) and result despite proper use of the medication or vaccine.
- Adverse effect: An unexpected effect that occurs after receipt of a medication or vaccine, which may or may not be caused by the medication or vaccine.
Watch this short video to learn more about the differences between side effects and adverse effects.
Side effects after COVID-19 mRNA vaccines
People are sometimes surprised when they have a side effect following a vaccine or medication, and they may perceive these effects as problematic. But, side effects do not mean there is a problem. For example, the two new mRNA COVID-19 vaccines have resulted in side effects, such as:
- sore arm (at injection site)
- muscle or joint aches
- fever or chills
These side effects typically occur in the first few days after receiving the vaccine, and in the case of both new mRNA COVID-19 vaccines, the side effects were more likely after the second dose. Further, younger people were more likely to experience side effects than older people. So, why does this happen and what does it mean related to the COVID-19 mRNA vaccines?
- In some cases, side effects indicate that your immune system is working to defend against the vaccine. Side effects are often part of the immune response generated by our bodies. For example, aches and pains result from changes that we can’t see, like swelling, as immune system cells move into the area where a “foreign invader” has been identified. Redness can result from increased blood flow to the area of the immune response, and fever is the body “turning up the temperature” to increase the effectiveness of the immune system and decrease the effectiveness of a perceived pathogen. As you might have realized, many side effects are things we describe as symptoms when we are sick, but in that case, too, it is our immune system responding to a “foreign invader.”
- Side effects occur in the first day or two after the vaccine because the immune system is working. After a vaccine is administered, it takes several hours for the immune response to “ramp up” and respond to what it perceives as a “foreign invader.” Often, the first effects will be closest to the injection site, like pain and redness at the site of the injection, with later effects being further from the injection site or widespread, like fever.
- The greater number of side effects after the second dose and among younger recipients suggest that mRNA vaccines invoke strong immune responses. So, even though side effects might make you “feel sick,” you aren’t actually infected. Your immune system is just responding to the vaccine. Like a fire drill, the COVID-19 vaccine trains your body to protect you from SARS-CoV-2 if you are exposed to it in the future.
Adverse events after COVID-19 mRNA vaccines
So far, one adverse event following COVID-19 mRNA vaccines has been identified. Specifically, a small number of people have had severe allergic reactions, called anaphylaxis. Currently, it is estimated that this severe allergic reaction has occurred in about 11 of every 1 million people who got the vaccine. Because these types of allergic reactions tend to occur very quickly after someone gets the vaccine, people are being advised to stay at the site where the injection was given for 15 to 30 minutes after getting vaccinated. No one has died from this reaction. Likewise, scientists and public health experts have systems in place to learn more about these reactions as well as monitor for other adverse events on an ongoing basis.
Think about it:
- Do you think some people might confuse side effects with actual illness? Why or why not?
- Why do you think some people experience side effects, but others do not?
- If a person experienced a physical condition in the days after receiving a vaccine, like indigestion or a racing heart, do you think they might believe the vaccine was the cause even if the evidence proved otherwise? Why or why not?
Unit 1, Lesson 2 – The Innate Immune Response
What to Expect after Getting a COVID-19 Vaccine, CDC
Side Effects and COVID-19 Vaccines: What to Expect, John Hopkins Bloomberg School of Public Health
How do we know COVID-19 vaccines are safe?
Even though COVID-19 vaccines were created faster than other vaccines, their safety has not been compromised. So, how do we know?
To start, let’s look at this short video from the Centers for Disease Control and Prevention, The Journey of Your Child’s Vaccine, to see how vaccines are normally made.
- This infographic summarizes the points made in the video and can be used as a reference for reading the rest of this article.
So, now, let’s take a look at how COVID-19 vaccines were made using the 3 parts of the journey described in the video.
Part 1: Development, approval, and manufacture of a vaccine (purple part of the infographic)
For COVID-19 vaccines, a few changes were made to shorten the process of making the vaccines. Importantly, these changes did not sacrifice measures of vaccine safety.
- Change #1: Phases 1 and 2 of clinical trials were combined, so that the timeline could be shorter.
- Change #2: Vaccine batches (lots) were made and tested while phases 1, 2 and 3 of clinical trials were being completed. Normally, this work would not happen until after the Food and Drug Administration (FDA) licensed the vaccine. But, by doing these steps in parallel for COVID-19 vaccines, as soon as the FDA approved a vaccine, doses were ready to ship. If the vaccine was not approved by the FDA, these doses would have been thrown away.
One important thing that did not change was the size of the phase 3 trials for COVID-19 vaccines, which included tens of thousands of participants. For example, the Pfizer phase 3 trial included about 38,000 people, and the Moderna phase 3 trial included more than 30,000 people. Trials of this size may not reveal rare adverse effects, but they are large enough to find major safety issues.
Another important thing that did not change during COVID-19 vaccine development was the review process. When the data are submitted to the FDA, a special committee, called the Vaccine and Related Biologics Product Advisory Committee (VRBPAC), a group of independent experts, study the data to understand how safe and effective the vaccine is. They share this understanding with the FDA to help the FDA make their decision about whether to accept or reject the vaccine.
Part 2: Adding a vaccine to the immunization schedule (orange part of the infographic)
COVID-19 vaccines are not being added to the childhood immunization schedule, but they still go through this part of the process after the FDA’s approval process is finished. During this phase, another group of experts reviews the data. They are part of the Advisory Committee on Immunization Practices (ACIP). This committee offers guidance to the Centers for Disease Control and Prevention (CDC). They review the data and make recommendations about who should or should not get the vaccine. Even for a vaccine that will only be given to adults at first, like the COVID-19 vaccine, this committee still considers questions like:
- How safe is the vaccine for people of different ages?
- How well does the vaccine work in different age groups of people?
- How serious is the disease in different groups of people?
- How many people would get sick without the vaccine?
The CDC considers the insights offered by the ACIP to create “recommendations,” which are the rules that doctors and other healthcare providers use to decide who should or should not get the vaccine.
Since COVID-19 vaccines will eventually also be given to children, this committee will meet again to make rules related to the use of these vaccines in children.
The ACIP usually meets three times per year, and new vaccines are added to the agenda at that time. For COVID-19, as soon as the FDA approved each vaccine, the CDC held emergency meetings a few days later to review the data and make recommendations. In this way, the timeline was also shortened because the companies did not need to wait until the next scheduled meeting. (For more information about the CDC’s part of the process during COVID-19, check the “Related Resources” section for a link to the video, How CDC is making COVID-19 vaccine recommendations.)
Part 3: Continuing to monitor vaccine safety (green part of the infographic)
By the time a vaccine can be given to the public, the data from phase 3 trials have been reviewed by dozens of independent experts, but that does not mean that the FDA and the CDC are done monitoring the vaccine. As described in the video and shown on the infographic, several different systems monitor vaccine safety:
- Vaccine Adverse Events Reporting System (VAERS)
- Vaccine Safety Datalink (VSD)
- Post-licensure Rapid Immunization Monitoring System (PRISM)
- Clinical Immunization Safety Assessment Project (CISA)
These systems work in different ways, so that the FDA and the CDC have many chances to look for vaccine safety concerns.
For COVID-19 vaccines, the CDC will use two extra monitoring systems:
- V-safe – This new smartphone-based monitoring system allows the CDC to communicate with people who recently got the COVID-19 vaccine through texts and web surveys to see how they are feeling.
- National Healthcare Safety Network (NHSN) – This system is not new, but it will help monitor COVID-19 vaccinations at long-term care facilities, like nursing homes.
- Changes to part 1 made the process shorter, but did not delete any part of the process.
- The same was true for part 2.
- Part 3 is always ongoing for any vaccine, but extra monitoring has been added for COVID-19 vaccines.
Think about it:
- After learning about the changes for COVID-19 vaccines, which changes do you think were most helpful for quickly creating a vaccine?
- Were there changes that you feel should not have been made?
- As a class, discuss the ethics of vaccine development during a pandemic. On one hand, a vaccine is needed as soon as possible so fewer people die from the disease. But, on the other hand, vaccine safety is even more important because the vaccine will be given to millions of people in a short period of time.
- Many people are concerned about the safety of COVID-19 vaccines because of the short amount of time in which they were made. What do you think is the most important thing for these people to know? If you worked at the CDC, how would you get this information to people? For example, what message would you create and where would you share it?
The Journey of Your Child’s Vaccine (Video), CDC
The Journey of Your Child’s Vaccine (Infographic), CDC
Ensuring the Safety of COVID-19 Vaccines in the United States, CDC
COVID-19 Vaccines, FDA
Emergency Use Authorization for Vaccines Explained, FDA
How CDC is Making COVID-19 Vaccine Recommendations (Video), CDC
Can you explain how mRNA vaccines work?
Messenger RNA, or mRNA, is a nucleic acid that is common in our bodies. It is the link between DNA, our genetic code, and our body’s ability to make proteins. In short, mRNA is made from DNA in the nucleus of cells. The mRNA is then transported to the cytoplasm, where it serves as the blueprint during protein manufacture. So, how can it be used to help us make a vaccine?
With mRNA vaccines, instead of introducing a weakened or inactivated pathogen, like other vaccines, mRNA is introduced as the vaccine. The mRNA that is chosen represents a part of the virus to which the body would make an immune response during an infection. In the case of COVID-19, the mRNA is against the SARS-CoV-2 spike protein. As cells generate and release the protein, the immune system recognizes the protein as “foreign” and works to get rid of it, generating an immune response.
mRNA vaccine technology has been studied in animals for many years, but COVID-19 mRNA vaccines are the first to be approved for use in people.
Watch a short video in which Dr. Offit discusses how mRNA vaccines work.
From DNA to Protein (Animation), Wellcome Genome Campus for yourgenome.org
Understanding mRNA COVID-19 Vaccines, CDC
Why do we need to wear masks, and what do we need to know about them?
SARS CoV-2, the virus that causes COVID-19 disease, is a respiratory disease, so it can easily spread from one person to another through the air by coughing, sneezing, or even talking. Since the virus particles are in the secretions from our noses and mouths, masks that cover both the nose and mouth serve as a physical barrier to the spread of the virus particles. In fact, a number of scientific studies have proven that masks can help decrease the spread of SARS CoV-2 virus when worn properly.
- Watch the short video on this page that shows the difference between how droplets spread with and without a mask.
Masks are most likely to reduce the spread of COVID-19 when most people in public settings use them. The Centers for Disease Control and Prevention (CDC) recommends that people wear a mask in public and whenever they are around people who do not live in their household. People taking care of someone in their home who is ill with COVID-19 should also wear a mask. Masks help in two ways:
- If you are infected, even without symptoms, you have a lower chance of spreading the virus to others.
- If virus particles are in the air, because someone near you is infected, you have a lower chance for virus particles to enter your nose or mouth as you breathe.
These measures are particularly important because SARS-CoV-2 can spread even when people do not have symptoms of COVID-19. Scientists estimate that up to 4 of every 10 people infected with SARS-CoV-2 do not have any symptoms, so they can spread the virus and never know that they did it.
Think about it:
Can you name any other viruses that might be stopped by masks? Why do you think masks are not recommended to stop those viruses?
Proper mask wearing
Did you know there are steps to follow when you are putting on a mask or taking one off?
Putting on protective equipment, like a mask, is called “donning.” Proper mask donning involves these steps:
- Wash your hands or use hand sanitizer that contains at least 70% alcohol to make sure your hands are clean before you touch the mask.
- Put the mask over both your mouth and nose, and make sure it is secure under your chin without any gaps.
- Make sure the mask fits snugly around your nose. If it has a metal band at the top, shape it so that air is not escaping through the top of your mask.
- Check to see that the mask fits snugly on both sides of your face without any gaps.
- Make sure you can breathe and talk easily with the mask in place.
While wearing your mask:
- Try not to touch the mask while you are wearing it. If you do touch the mask, either wash your hands with soap and water or use hand sanitizer containing at least 70% alcohol to disinfect your hands.
- Be sure to wear your mask properly. Look at the examples below to see correct and incorrect ways to wear your mask:
Taking off protective equipment, like a mask, is called “doffing.” Proper mask doffing involves these steps:
- Whenever you are removing or handling your mask, be careful not to touch your mouth, eyes, or nose.
- Only touch the mask by the ear loops or the tie behind your head. This is to avoid any germs that are on the mask itself.
- Loosen the band around the ears or untie the band behind your head.
- If you will be discarding the mask: Fold the outside corners of the mask together, so the part that was facing “the world” is on the inside. That helps keep any virus particles that could be on the mask away from your hands.
- If you will need to use the mask again: Sometimes if you are at school or at a restaurant, you will need to take your mask off for a short time and then use it again. In these cases, fold the outside corners of the mask together, so that the part that was touching your face is on the inside. That way, when you put the mask on again, the “inside” of your mask will not have touched any surface that could be contaminated with the virus. Try to place your mask on a clean surface or in a place where it will not be disturbed until you need it again.
- If the mask is disposable, throw it in a trash receptacle. If it is washable, put it in the laundry. When it is washed, soap and hot water should be used, and it should be dried in the dryer.
- Wash your hands immediately after you remove the mask and place it in the trash or laundry receptacle.
Doctors, nurses, and other healthcare providers are used to donning and doffing protective equipment because they have to do it all the time to protect themselves and their patients.
Types of masks
Masks should be worn when interacting with others, especially anyone who does not live in your home, and masks should not be shared with others. Everyone should have their own. Children under 2 years of age and people who have trouble breathing with a mask or who could not remove the mask without help should not wear masks. In these situations other precautions, like hand washing and social distancing, are even more important, as is the need for those around these individuals to wear masks.
Several types of masks are effective against COVID-19. A study conducted at Duke University showed that the best masks include three-layer surgical masks as well as those with 2 layers of cotton material. Homemade masks are effective as long as they are made of 2 layers of cotton. Another study from the University of Arizona showed that masks made from tea towels, cotton-blended fabrics, and antimicrobial pillowcases were protective. The authors reported that the more densely that the fibers are packed in a material, the better it is at filtering, and, therefore, the better it will be as a mask. So, for example, materials with higher thread counts are more protective.
Several types of masks have been found not to work very well. For example, handkerchiefs or bandanas, neck gaiters, and knitted masks provided little protection against the virus in the Duke University study. The materials that were least effective at blocking the virus in the University of Arizona study were scarves and those made from cotton t-shirts.
Other masks, including N-95 and N-99 masks, are very effective against the virus, but due to their short supply, they are reserved for health care personnel.
- Check out the types of masks tested in the study from Duke University.
- Check out the types of masks tested in the study from the University of Arizona.
Think about it:
These two studies both aimed to learn about what types of masks are most effective, but they were conducted in different ways. After reviewing them, think about whether one method seems better than the other. Why? Why do you think it might be important for studies answering similar questions to be done in different ways? What benefits might this provide? What drawbacks might there be?
How to Wear a Mask, CDC
Coronavirus Face Masks & Protection FAQs, Johns Hopkins
Q&A: Masks and COVID-19, World Health Organization (WHO)
WHO’s recommended fabric mask materials and composition, WHO
What is "contact tracing?"
Contact tracing is a pillar of infectious disease control in public health. It is a well-tested technique for controlling diseases that spread from person-to-person. In fact, contact tracing was central to the eradication of smallpox. Public health officials used exhaustive contact tracing to find all infected individuals. By isolating infected persons and immunizing contacts, and members of the surrounding community, the spread of smallpox was completely stopped.
So, how does contact tracing work?
The basics of contact tracing
When public health officials identify infected people, they interview them about whom they had recently contacted. For COVID-19, this means identifying who people had contacted 2 days before symptoms started through the time when they started isolating.
Knowing these people, called “contacts,” may have been exposed to the disease, officials reach out to alert them of possible exposure and collect information from them. In this manner, contacts can be tested, isolated, and treated if infected. Likewise, their contacts can also be identified – essentially, the second generation of contacts.
Goals and timing of contact tracing
Contact tracing can reduce the spread of infections in a community by:
- Interrupting person-to-person transmission
- Offering diagnosis, counseling and treatment to individuals who are already infected
- Alerting contacts that they might have been infected and providing counseling or care to decrease the chance of becoming sick
- Learning more about how the disease moves through communities
In contact tracing, time is of the essence. The longer it takes to identify contacts, the more people they will be in contact with. Ensuring that contacts do not interact with others is critical to protecting communities from further spread. Whereas people with influenza infect an average of two additional people, those infected with COVID-19 are estimated to infect about six additional people when doing day-to-day activities in the community. If communities are not able to effectively isolate infected patients and ensure that contacts can separate themselves from others, diseases can rapidly spread.
Contact tracing and COVID-19
Contact tracing is an important part of the current COVID-19 pandemic for a few reasons:
- Almost everyone is susceptible to infection.
- We don’t yet have effective prevention measures (e.g., vaccines).
- We are still learning what testing results mean.
- We don’t have many effective treatments yet.
A person is identified as a contact of a COVID-19-infected person if they have been within 6 feet of that person for a period of at least 15 minutes without wearing personal protective equipment.
Based on what we know about the virus at this point, contacts of people infected with COVID-19 are encouraged to stay home for 14 days after their last interaction with the infected person and maintain social distance — at least 6 feet — from others.
Identified contacts are also instructed to:
- Monitor themselves for symptoms, like cough or shortness of breath
- Check their temperature twice daily
Sometimes public health staff will check in with identified contacts to make sure they are self-monitoring and have not developed symptoms. Typically, once contacts have been identified, they will be given information about how to get in touch with the health department. If a contact develops symptoms, they will be evaluated for infection and need for medical care.
Because contact tracing is one of the best tools we have to stop the spread of COVID-19 at this point, it is critical that anyone identified as infected, or a contact of someone who is infected, follow the instructions they are provided.
What is a "cytokine storm?"
Some patients with COVID-19 have been reported as experiencing an overreaction of their immune system, referred to as a “cytokine storm.”
Cytokines are chemical signals that enable communication between parts of the immune system, triggering specific cells to respond to a pathogen.
Cytokine storms are not unique to COVID-19; they can occur during other infections as well.
Find out more:
- Cytokines – See “Preparing for battle” in the “Adaptive immune system” section of this page.
- General information about cytokine storm – See bottom of the section titled, “Unnecessary or overzealous immune responses” on this page.
- COVID-19 cytokine storm and research occurring at CHOP – “Multidisciplinary Team Studies Cytokine Storms Brewing in COVID-19,” by Jillian Rose Lim, CHOP Research Institute Cornerstone Blog.
Can you explain COVID-19 testing?
We have been hearing a lot about testing during the coronavirus pandemic, so let’s take a closer look. Discussion about testing related to COVID-19 refer to two different types of testing – infection testing and antibody testing. Infection testing measures the presence of virus in a person’s respiratory secretions. In contrast, antibody testing, as it sounds, measures the immune response after an infection by testing for antibodies that a person has against the virus. Antibody tests require blood samples instead of respiratory secretions.
This is the first kind of test we heard about when the pandemic started, and it continues to be important. Infection testing tells whether a person is currently infected with the virus. Most of these tests involve swabbing the nasal cavity to collect respiratory secretions that may contain the virus.
These samples are processed using a lab technique called reverse transcriptase polymerase chain reaction, or RT-PCR. Lab technicians isolate coronavirus RNA from the nasal sample and using the enzyme, reverse transcriptase, they create “complementary DNA,” or cDNA. The cDNA is like a model, or pattern, that can be used to make copies of DNA that mimic a portion of the coronavirus RNA. To do this, technicians add a few other reagents to the sample before placing it in a piece of lab equipment, called a PCR machine, which is programmed to the conditions needed to build DNA. The other reagents include:
- A piece of DNA that matches the part of the cDNA that they wish to amplify, or copy. This is called a primer.
- Deoxyribonucleotide triphosphates or dNTPs, which are the building blocks to make more DNA. These are more specifically known as dATP (adenine), dGTP (guanine), dTTP (thymine) and dCTP (cytosine).
- An enzyme that will allow for more DNA to be produced, called DNA polymerase.
- One other important agent that is added to the PCR sample is a fluorescent marker that enables scientists to determine whether the sample is positive or negative.
If the patient sample had coronavirus RNA, at the end of the PCR process, the sample will have many copies of DNA that contain the fluorescent markers. If the sample did not have coronavirus RNA, the sample will not have new copies of DNA, and, therefore, will not fluoresce. Fluorescent markers can be detected in a few ways:
- In some labs, the PCR machine is connected to a computer and includes a component that can detect fluorescence. This is called “real-time RT-PCR” because scientists can monitor fluorescence as the PCR reaction occurs. This approach results in safer and faster processing of samples.
- However, in many cases, the PCR samples are subjected to a second assay, called an enzyme-linked immunoassay or ELISA. In this method, rather than using fluorescent markers, other molecules will be used as markers. During the ELISA, the molecular markers will be detected by specially labeled antibodies that bind to them. Through a series of additional steps, the labeled antibodies will be detectable by a color-based reaction that is analyzed using a special piece of equipment made for reading these color changes in ELISA samples.
In the case of the current pandemic, the important result is qualitative, meaning knowing whether the sample was positive or negative. However, in other situations RT-PCR can be used to generate quantitative information, meaning that scientists can measure differences between the amount of RNA or DNA in the starting samples.
Infection testing will remain important for determining when individuals are infected with COVID-19, so this type of testing will continue to be used to diagnose patients.
Watch this short video to hear how scientists and clinicians at CHOP developed a COVID-19 infection test.
More recently, we have been hearing about antibody testing. Antibody tests are important for a few reasons:
- They can determine who was infected previously, including people who did not feel sick or have symptoms, called asymptomatic.
- They can be used to determine who can be a plasma donor for the treatment approach currently being tested to help coronavirus patients recover.
- They will be critical for learning more about who is protected from infection, particularly during vaccine trials.
While this testing is essential, it is important to realize that right now, we are still learning about this new virus, so it will take time for scientists to understand exactly what antibody test results mean. Specifically, we need to understand:
- When was someone infected, and how long will their antibodies last? Right now, we do not know how long antibodies will remain after coronavirus infection. Typically, when someone has an infection, antibody levels increase in the first week or two after exposure, and after recovery, the levels decrease over time. For most infections, even if antibodies are not detectable with a clinical test, the person still has immunologic memory. With immunologic memory, if the person is exposed again, their immune system can respond more quickly. Likewise, the antibodies generated from memory cells are more adept at stopping infection than those generated during primary, or first, infection. Based on historical studies with human coronaviruses, it is expected that immunologic memory generated after infection will protect people from having moderate or severe disease, even if they are infected again, but this needs to be confirmed for COVID-19 virus.
- What type and quantity of antibodies are needed to prevent infection? Right now, we also do not know what type of antibodies (See “Adaptive immune system” on this page of the VEC website for a description of antibody types) will be most effective at preventing infection and how high the level of antibodies needs to be for protection. In addition to better understanding the different types of antibodies, it is also important to make sure that the antibodies are capable of neutralizing the virus, not just binding to it. This means scientists need to understand how the antibodies function. Typically, when making a vaccine, scientists want a “marker for efficacy,” meaning some measurement that indicates the vaccine works well enough to prevent people from getting sick if they are exposed to the virus (i.e., generates sufficient quantities of antibodies as well as antibodies capable of neutralizing the virus). Because COVID-19 is a new virus, scientists do not have enough experience yet to have defined this type of marker.
Two additional challenges to the current antibody testing situation involve the development of early tests. First, because of the emergent nature of the situation, the Food and Drug Administration (FDA) is allowing some tests to be used before the typical FDA reviews have been completed. So, some tests will ultimately not meet with FDA standards. Antibody tests need to be both sensitive and specific:
- Sensitivity means the test needs to accurately detect positives, or, said another way, it needs to accurately detect who had disease.
- Specificity means that the test should not result in false positives; that is, it should not give a positive result when the person does not have coronavirus antibodies.
Scientists aim for tests that accurately measure sensitivity and specificity about 99 of 100 times, essentially only missing 1 positive person and only falsely identifying 1 person as positive, when they are actually negative. Because the tests are not all reviewed before being available, we do not know the sensitivity and specificity of all tests. A small study of several tests found a wide range of sensitivities and specificities (Lassaunière, 2020).
Second, scientists still need to figure out the timeline related to infection and development of the immune response to understand the best time to use antibody tests. For example, someone may have detectable antibodies, suggesting that they had an infection, but they may also still be infectious. In other words, they could have both a positive infection test and a positive antibody test. The relative timing related to the presence of virus in a person’s secretions and the detection of antibodies in their blood still needs to be better understood, especially if politicians aim to use antibody testing data as a means for deciding when to reopen communities.
Two types of antibody tests are being developed – lab-processed and point-of-care tests:
- Lab-processed tests require sending the blood sample to a clinical laboratory, where the samples are subjected to an ELISA assay. These blood samples are collected by insertion of a needle into the patient’s arm. The ELISA assays used to process blood samples are similar to those mentioned as part of the PCR process in the “infection testing” section (above) in that they employ antibodies and color-change-based reactions. However, they use different reagents, so that the results measure COVID-19-specific antibodies in a person’s blood (rather than the DNA generated during PCR). Some of the lab-processed tests being developed measure any COVID-19 antibodies, but others measure specific sub-groups of antibodies, like IgG or IgA. (See “Adaptive immune system” on this page of the VEC website for a description of antibody types.)
- Point-of-care tests are processed at the time the blood is taken from the patient. These are the type that have been shown being used at drive-through testing sites on the news. Samples are typically obtained by a prick of the finger, and the blood wicks into a narrow tube before immediately being added to a small cassette, which is about the size of a microscope slide. Within 10-15 minutes, the results show whether a person has COVID-19 antibodies. Typically, these tests measure IgM or IgG antibodies.
While point-of-care tests are faster and easier to process, they can only determine positive or negative results (qualitative) and may prove to be less accurate.
The conundrum that we currently face is that to develop policy, large portions of the population will need to be tested, so a faster antibody test that requires less blood, such as the point-of-care tests offer, would be much more conducive to getting a large amount of information quickly. However, results from these tests need to interpreted with caution until scientists can determine their accuracy and limitations. Likewise, since several different point-of-care tests are available, and since their quality is likely to vary, comparing data generated from areas using different tests is also likely to be problematic.
Both infection and antibody tests will continue to be necessary in controlling COVID-19.
Selected references and resources
- Daly, J. 2020 Mar 27. Here’s how coronavirus tests work – and who offers them. Scientific American. https://www.scientificamerican.com/article/heres-how-coronavirus-tests-work-and-who-offers-them/
- Lassaunière R, Frische A, Harboe ZB, et. al. 2020. Evaluation of nine commercial SARS-CoV-2 immunoassays. MedRxiv preprint doi: https://doi.org/10.1101/2020.04.09.20056325.
- Mallapaty, S. 2020 April 18. Will antibody tests for the coronavirus really change everything? Nature. https://www.nature.com/articles/d41586-020-01115-z
What are the similarities and differences between influenza and novel coronavirus?
There have been some questions about whether influenza and coronavirus are similar. So, let’s take a closer look.
While influenza and COVID-19 are both enveloped viruses that contain RNA, they are not related. Influenza viruses are from the family Orthomyxoviridae, whereas coronaviruses are from the family Coronaviridae. See more details:
- Both have envelopes. Viral envelopes are made of lipids, which are a type of fat molecule that cannot dissolve in water. However, these molecules are easily damaged by disinfectants, which is why soaps, alcohol-based hand sanitizers, and many cleaning agents can reduce the chance of infection with both.
- Both have protein spikes that help them attach to cells. Influenza viruses have two surface proteins, called hemagglutinin and neuraminidase. These two spike proteins are commonly used to distinguish among different influenza viruses (e.g., H1N1, H2N3, etc.) The protein that causes the spikes on COVID-19 (and other coronaviruses) is generally referred to as “S protein.”
These spike proteins determine what parts of the cell surface the viruses attach to when they infect people. Influenza viruses bind to sialic acid, whereas coronaviruses bind to an enzyme receptor, commonly referred to as ACE-2. Preventing binding of the virus to the cell surface is one way to prevent infection, so this information is important for the development of treatments and vaccines.
- Both contain RNA. Influenza viruses and coronaviruses have nucleic acids that are single-strands of RNA. In contrast, human cells contain double-stranded DNA. Like individual strands of DNA, RNA is labelled as “positive” or “negative.” These labels relate to how the strands are used during replication. Positive strands of RNA can be used as a roadmap during protein production (translation), but negative strands must first be made into a template (transcription) before proteins can be produced. Coronaviruses contain positive strand RNA, whereas influenza viruses have negative strand RNA.
Another difference between the RNA contained in these two types of viruses is how it is contained in the cell. The RNA in coronaviruses is one long strand; this is called a non-segmented genome. In contrast, the RNA in influenza viruses is segmented, meaning it is in several pieces. Influenza type A, which is the type that can cause pandemics, contains eight segments of RNA, as do influenza type B viruses. Other types of influenza viruses, called type C and type D, have seven RNA segments.
- Both can infect animals and people. One of the reasons viruses from both of these families can cause pandemics is because they can change rapidly when they “jump” from animals to people. Typically, the types of a virus that infect people are less capable of infecting animals and vice versa. So, for example, a human influenza virus would not typically infect a chicken. However, on occasion, genetic changes enhance the ability of an animal virus to infect people. If this genetically altered virus can also replicate efficiently and be easily transmitted from person to person, it has the ability to spread throughout the population. This is what happened with the novel coronavirus.
Although these lists may not be exhaustive, they offer a glimpse of how many different types of animals both of these families of viruses can infect:
- Influenza viruses can infect birds, aquatic birds, pigs, horses, dogs, cats and sea mammals.
- Coronaviruses can infect bats, pigs, cats (domesticated and non-domesticated), dogs, rabbits, mice, rats, cows, chickens, turkeys and pangolins.
Transmission and Illness
Some of the confusion about whether these viruses are related might have come from the similar ways they are transmitted and some of the symptoms they cause.
- Both are spread by respiratory droplets. Because both of these viruses reproduce in cells that line the respiratory tract, they can be spread in respiratory secretions, such as from coughs and sneezes. Likewise, when these secretions land on objects that are subsequently touched by others, virus particles can spread to hands. If that person then touches their eyes, nose or mouth, the virus can infect them. This is why protective practices, like covering coughs, washing hands, and using masks, have been promoted during the coronavirus pandemic.
- Both can cause similar symptoms. Some people who get infected with influenza will not have any symptoms. The same is true of those with coronavirus infections. Most people, however, will have mild symptoms. Symptoms of both infections can include coughing, extreme fatigue, fever, headache, muscle aches, and runny nose or congestion. Some people with coronavirus may also have difficulty breathing, sore throats or diarrhea. More people will become severely ill with COVID-19 than what is typical with influenza virus infections. According to current data, up to 15 of every 100 people will need oxygen and about 5 of every 100 will become critically ill.
- Both are dangerous for older people and those with chronic conditions of the heart and lungs. Because both of these infections affect the lungs, those with chronic conditions of the heart or lungs are more likely to become severely ill. Likewise, others who are immune compromised, such as elderly people, are also at increased risk for complications when infected with either of these viruses. Early data suggest, however, that while pregnant women are at increased risk of severe pneumonia with influenza as compared to women of the same age who aren’t pregnant, they do not appear to be at higher risk with coronavirus.
Treatments and vaccines
While antiviral medications and vaccines are available to fight influenza, the same is not currently the case for COVID-19, since it is a new virus. However, many scientists around the globe are working to better understand which treatments will work and how to create an effective vaccine. Because these viruses are different, previous influenza infections or vaccination against influenza will not protect against infection with coronavirus. Nor, will treatment with the same medications necessarily be effective.
What will staying at home do to help with the virus, and what does flattening the curve mean?
COVID-19 can infect anyone who is not immune. People can become immune to a pathogen in two ways – through infection or vaccination. Therefore, in the absence of vaccines, the only way for people to become immune is by infection.
The issue, however, is that because COVID-19 is a new virus, billions of people lack immunity. So, if everyone continued with their daily activities, the virus would spread very rapidly through the population. While this would quickly increase immunity among the population at large, and many individuals would have mild, or non-existent, symptoms, that would not be the case for everyone. Not only would some people have severe and fatal infections, this approach would also overwhelm healthcare systems, resulting in even more deaths than necessary.
In an attempt to prevent this, public health officials have implemented social distancing to slow the spread of COVID-19. By staying apart, we will decrease the number of people with infections at any one point in time. This will cause the curve to stay lower over a longer period of time, hence the term “flattening.”
You can think of “flattening the curve” like eating at a buffet. Overfilling your plate in a single visit to the buffet will be faster, but you will lose more food than if you make several trips and fill your plate with small amounts each time. If your plate is heaping, food is more likely to be wasted when it falls off your plate on the walk to the table, when the table gets bumped, or when it mixes flavors with other foods on your plate. On the other hand, if you make multiple trips to the buffet, you will not lose as much food to the floor, table or because of mixing flavors. In the case of the pandemic, the stakes are higher because we are not losing food, we are losing family, friends and neighbors. By flattening the curve, we are giving healthcare providers a situation more akin to multiple trips to the buffet — fewer patients at once and more time to restock and regroup along the way.
This approach is also important for another reason. It lengthens the timeline for the population to gain immunity. While this might seem counter-intuitive since we want people to be protected, this approach allows scientists more time to create a vaccine. With a safe and effective vaccine, people can become immune without the chance of experiencing severe, or fatal, infections. Since we don’t know which people will get critically ill, or die, from their infections, vaccination removes the risk that is inherent in experiencing natural infection.
In sum, flattening the curve helps us in three major ways:
- Keeps the medical system from being overwhelmed
- Provides time to develop a vaccine
- Prevents more deaths
What kinds of vaccines are being studied?
One way that we hope to eventually protect ourselves from COVID-19 is by vaccination. Vaccines introduce our immune systems to a pathogen without causing disease. When people are infected with a pathogen, like the virus COVID-19, we don’t know who will become severely ill, or even die, from the infection. So, if people can become immune without getting sick, we can decrease the number of people who are hospitalized or die.
Right now, we don’t have a vaccine against COVID-19, but scientists are working to develop one. It will take several months to a couple of years to make a vaccine that has been sufficiently tested to ensure its safety and effectiveness. It will also take time to build supply, so that we have enough doses to protect large numbers of people. But, in the interim, people are, understandably, curious about how scientists are trying to make a vaccine.
Several groups of scientists are working on vaccine development, and as is typical in science, they are trying different approaches. Over time, we will see which methods work best. The approaches can be categorized into two types – those that have been used to create one or more existing vaccines and those that aren’t made in a similar manner to any current vaccines.
Previously employed approaches
Four previously successful approaches are all being examined in the effort to develop a vaccine against COVID-19:
- Inactivated vaccine – Like influenza and polio shots, this approach uses killed whole virus to make the vaccine.
- Subunit vaccine – Like hepatitis B, shingles, and HPV vaccines, this approach uses part of the pathogen to make the vaccine, like a protein or polysaccharide. The part of the pathogen chosen is that which generates immunologic protection.
- Weakened, live viral vaccine – Like measles, mumps, rubella and rotavirus vaccines, this approach involves growing the virus in cells in the lab to weaken it, so that it replicates in vaccine recipients without causing illness.
- Replicating viral vector vaccine – Like the Ebola and Dengue vaccines, this approach involves putting a gene for a protein of interest (e.g., one that will protect against disease) into a virus that will not cause illness, but will cause an immune response. These viruses are called vectors; examples of vector viruses include yellow fever vaccine virus and vesicular stomatitis virus. When the viral vector reproduces in the vaccine recipient, the protein of interest is also produced, so immunity is generated against that protein as well.
Promising new approaches
Three approaches, that are theoretically useful, but from which products have not resulted to date, include:
- DNA vaccine – Plasmids are small circular fragments of DNA. DNA vaccines are made of plasmids that have genes of interest inserted. When the plasmids are injected into muscle cells, the DNA is treated like cellular DNA, which means it is transcribed into messenger RNA (mRNA), from which proteins are produced. In this manner, the cell will produce a protein that the body realizes is foreign and creates an immune response against. Clinical trials of HIV and influenza vaccines have used this approach, but, to date, the approach has not resulted in a vaccine that is routinely used.
- mRNA vaccine – In this approach, the mRNA is the vaccine, so unlike DNA vaccines, the response does not rely on DNA being converted to mRNA, essentially cutting out a step. Like DNA vaccines, this approach has been tested in small trials, but experience with this approach is even more limited than with the DNA vaccine approach.
- Non-replicating vector vaccine – Similar to the replicating viral vectors (described above), a gene of interest is added to a vector, like vesicular stomatitis virus or yellow fever vaccine virus, and delivered to the vaccine recipient.
Finally, worth noting, one type of passive immunity is also being explored. Passive immunity is protection afforded by someone else’s pathogen-specific antibodies. Typically, we think of maternal antibodies protecting babies, but passive immunity is used in other situations as well. Called immunoglobulins, this treatment with antibodies is often used to help people after a bite by a snake or rabid animal. But, this approach was also used before we had a diphtheria vaccine and in some cases, it is used in conjunction with vaccination, such as for newborns whose mothers are infected with hepatitis B. During the coronavirus pandemic, antibodies preparations from those who have recovered are being tested for their ability to help infected patients fight the virus.
- VMP Middle School Lesson 4, “On the Shoulder of Heroes: Toward a World without Polio.” In this lesson, students study the scientific process as it relates to our historical understanding of polio. Students research scientists or teams of scientists to understand who discovered what, when, where, and why. Activities include creation of a class timeline and map as well as a class discussion about how the activities illustrate the scientific process of gaining new knowledge.
- Making vaccines, website section, Vaccine Education Center at Children’s Hospital of Philadelphia
- Lurie N, Saville M, Hatchett R, and Halton J. Developing Covid-19 Vaccines at Pandemic Speed, New England Journal of Medicine, March 30, 2020.
What kinds of treatments work?
Scientists and healthcare providers do not know for sure what treatments will be most effective in treating this new virus. However, they have to make treatment decisions when patients are sick. For now, they are using information about how to treat related viruses, like SARS and MERS, and as time passes, they gather more knowledge about what works, or doesn’t, in COVID-19-infected patients. Of critical importance, however, is the realization that the only way to know if a treatment works is through scientific studies.
Types of studies and ethical considerations
Information about what works can be ascertained in a few different ways:
- Placebo-controlled clinical trials compare similar patients who did and did not receive a particular treatment. With treatment and control groups, clinicians and scientists can determine whether the treatment group improved or recovered more quickly than those who did not get the treatment.
- Retrospective studies evaluate medical records of patients after treatment has finished. These studies analyze how patients responded to certain treatments, compared with other patients who did not receive the treatment.
- In some cases, study participants do not need to be individuals who are infected. For example, people who have been knowingly exposed to the virus, such as close contacts of infected patients and healthcare workers, can be treated.
Regardless of the approach, before a study can be started, it must be reviewed and approved by a committee of experts at the institution where it is being conducted. This group is known as the Institutional Review Board or IRB. These people ensure that research participants are treated ethically and safely.
Possible COVID-19 treatments
Scientists and clinicians are working quickly to find possible treatments. They will consider treatments that are already used to treat other illnesses as well as newly developed, coronavirus-specific treatments.
So, what kinds of treatments are being studied and why?
- Antiviral agents – Medications that treat viruses can act in several ways, including preventing the virus from infecting cells, decreasing its ability to replicate, or stemming immune response to the infection. Some antiviral medications are currently being tested for their effectiveness in people before or after exposure to coronavirus, like close contacts and healthcare workers, in an effort to decrease the number of infections.
- Anti-parasitic agents – One medication that has received significant attention is hydroxychloroquine. This medication is typically used to treat malaria as well as some autoimmune diseases, like lupus and rheumatoid arthritis. In March 2020, the Food and Drug Administration (FDA) approved emergency use of hydroxychloroquine for treatment of COVID-19. If effective, the medication would control the immune response to infection.
- Antibiotics – Although antibiotics are not effective against viruses, azithromycin (commonly known as Z-pack) is currently being tested for its anti-inflammatory abilities. Azithromycin together with hydroxychloroquine is being evaluated as a coordinated approach to decreasing inflammation and suppressing immune system activity to control symptoms in severely ill patients.
- Anti-inflammatory agents – In some cases, people are getting severely ill because their immune system overreacts to the infection. This type of heightened response, sometimes referred to as a “cytokine storm,” can be the cause of severe illness in young, healthy people. When this happens, medications that inhibit the overzealous response may help. One example of a class of medications being tested in these cases is called “IL-1/IL-6 antagonists.”
- Vitamin C – Much discussion has also occurred around whether vitamin C would be helpful in treating or preventing coronavirus. No evidence exists that taking vitamin C would protect someone from becoming infected with COVID-19. Some studies are currently evaluating whether vitamin C given to hospitalized patients, together with other treatments, is effective. Data are not currently available to substantiate its effectiveness.
While several of these have shown promise anecdotally, to date, insufficient evidence exists to prove that any of them effectively treat COVID-19. Hopefully, soon, evidence will be available to inform treatment decisions.
April 2, 2020
Why don’t we close down society for influenza like we are doing for coronavirus?
Some people have asked why we are acting differently about coronavirus when we don’t go to the same efforts each year when influenza season occurs. In fact, every year hundreds of thousands of people are hospitalized and thousands die from the flu. Three reasons are behind this difference:
- Biology of the viruses – Before December 2019, COVID-19 was unknown. Because it is a new virus, officials do not know some of the most basic information about it. They do not know how well the virus spreads. They do not know how long or how severe illness caused by infection can be. They do not know which people are most at risk of being infected. In contrast, influenza virus is well studied. While the virus changes frequently and, therefore, is difficult to control, we still know much more about influenza than COVID-19.
- Susceptibility –The first group of ill patients were reported in China in late December 2019. Because this virus can cause illness and it is a new virus, virtually everyone on the planet could be infected with it. On the other hand, influenza viruses circulate every year, so most people have at least some immunity to influenza.
Because virtually everyone can get sick and we don’t know as much as we need to about how to control the virus, it could spread very quickly. If too many people get sick at the same time, the healthcare system will not be able to attend to everyone.
- Treatment and prevention – In addition to having a large number of people susceptible to COVID-19, officials also do not know how to treat or prevent COVID-19 since it is such a new virus. In contrast, both antiviral medications and influenza vaccines offer tools to keep large numbers of people from becoming very sick and dying from influenza virus.
Over time, we will learn more about COVID-19, more people will develop immunity, and tools will be developed to defend ourselves against this virus. When that happens, dramatic measures like those we are using in 2020 will be less necessary.
How did this new virus form?
All organisms use genetic material to guide their reproduction. Genetic material can change in two ways during reproduction:
- Replication errors – During replication, sometimes an error is inadvertently introduced. It is called a point mutation. These small errors may have no effect, or they can be significant enough to cause disability or death of the newly replicated progeny.
- Introduction of new genetic material – Sometimes genes from one virus can enter cells and mix with genes from another virus that entered the same cells. The new genetic material can, as described above, have little to no effect, or it can cause a significant change in the virus.
Scientists are still working to understand exactly how COVID-19 developed, but genetic studies have provided some information. More than 95% of the genes are derived from a bat coronavirus. But, a critical part of the genes, related to how the virus attaches to cells, is different. That genetic information is more similar to a coronavirus found in pangolins, a type of anteater. Scientists are still working to figure out how another critical change occurred as well. This change is related to how infectious the virus is and which types of organisms it can infect. Scientists think that either the genes changed in another type of animal, yet to be identified, or this virus was spreading undetected among people without causing illness. Then, while it was reproducing in people, the genetic material changed again enabling the virus to become more infectious.
How Do Viruses Reproduce? (Animation) – This less than 2-minute animation describes how viruses replicate. Versions for elementary, middle or high school/college students are available with voice-overs adapted for each age group.