Wednesday, March 31, 2021

Vaccine, vaccine, vaccine, vaccine! (To the tune of "Jolene")

It's been a full year since I last posted! I'll have to go back to that one and see what needs to be updated since we've learned so much about severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). That's for another day, but I'll give you one comparison. At 3:08pm on March 15th, 2020 there were 162,687 cases of COVID-19 reported around the world, according to a dashboard created by the Johns Hopkins Centers for Systems Science and Engineering. At 11:28am on March 28th, 2021 there were 126,911,173 reported cases globally. That is staggering and, by all accounts, a gross underestimate. Remember the iceberg analogy. People who either don't get sick or only feel a little sick are far less likely to be tested, even during a pandemic, so we don't have the whole picture.

The virus is still circulating in our communities and it isn’t going to just magically disappear any time soon. It's still infecting people at high rates and it's mutating, or changing, to become a better virus. To be the best virus you can be is to spread rapidly and keep your host alive so they can sneeze and cough and send you out into the world to infect another. Humans are working hard to find ways to slow down the spread and to keep people from getting severely ill or dying. It's been one year since the World Health Organization declared a pandemic. One year and we've got vaccines people! This is AMAZING. The best way to protect yourself from getting extremely sick with COVID-19 and needing to be hospitalized, or from dying, is to get vaccinated. If you don't want to listen to me, listen to Dolly Parton. Continue to avoid getting infected until you can get vaccinated. Keep wearing your masks, stop swapping air, wash your hands. You know the drill. 

There are three vaccines available right now in the United States. Do you know how they work? <Looks furtively left, then right. Leans in and whispers> I don't really know either. Let's find out together! Full disclosure: I am not a vaccine specialist, nor do I have any deep understanding of the immune system. Immunology, the study of the immune system and immune response, is super complicated. Like I don't even have the right words complicated. Like actual immunologists, the doctors and researchers who study immunity, say it's complicated to them. The descriptions you're going to read of immune responses to these vaccines are very high level and not in any way certain of what will actually happen in your body or my body or your neighbor's body. Let's learn anyway!

Microscopic image of two SARS-CoV-2 virus particles. They are both round with spikes all around the outer edge of the cell.

Image credit: NIAID-RML

The virus and disease.

Before we get started talking about vaccines, let's learn about the virus and the disease it causes. In terms of microbes, SARS-CoV-2 isn't very complicated. From the outside in, there are protein spikes on the outer layer of a fat coat that is protecting a single strand of RNA, or ribonucleic acid. You've heard of DNA, right? The double helix? The double-stranded stuff that contains all of the genetic information that makes you, you? Well, RNA is a single strand of the same type of genetic information. SARS-CoV-2 RNA contains the codes for how to make more virions. Virions are individual viral particles.

The protein spikes on the outer surface of the virus attach to receptors in your body called ACE2. These receptors are found on nearly every type of cell in your body (nose, lung, heart, kidney, brain, intestines) which is why we see symptoms ranging from common cold-like symptoms to loss of taste and smell all the way to organ failure. The viral particle spike attaches to an ACE2 receptor, enters the cell, trades out the cell's plans for its own, sits back with a cocktail and a smoke and watches the world burn. 

In the background is a house on fire, a fire truck, firefighters, and the homeowner. In the forefront is a little girl and her face has been superimposed with an artist rendition of the spike-covered coronavirus, SARS-CoV-2. The caption says Don't worry, it's just a cold.

Okay, not quite, the virus isn't a sentient being. Once the virus spikes have attached to the ACE2 receptors, the virus' fat coat fuses with the outer surface of the human cell and the RNA is released. Inside the cell, the RNA bumps into a ribosome. Ribosomes are the protein-making machinery of a cell. The ribosome reads the genetic information of the RNA strand like a blueprint and begins to make the parts of the virus - spikes, fat coats, some proteins, and more RNA. Then those parts are put into a little factory and transport system called the Golgi apparatus which assembles the parts into new individual virions, packages them, and sends them out of the cell. And so it goes; RNA becomes parts, the parts are assembled, and new virions are released. After time, virus overwhelms the cell and the cell self-destructs. All of the remaining virions are released into the body where they seek out ACE2 receptors on new cells or are picked up by respiratory droplets and leave out the nose and mouth. The process is exponential, meaning that one viral particle can result in hundreds of additional particles. Each of those go on to make hundreds more and they can quickly take over thousands of cells in your body, creating millions of virions. The image below is from a fancy microscope called an electron microscope. It is used to capture clear, multidimensional images of very tiny things like viruses. This is an image of a cell during death. The green parts are the cell and the little bumpy purple balls are SARS-CoV-2. One cell and hundreds of viral particles.

Electron microscope image of a cell during death, or apoptosis. The cell is colored bright green and is covered in small bumpy purple balls. The purple balls are viral particles of SARS-CoV-2, the virus that causes COVID-19.
Image credit: NIAID-RML

For any of that to happen, you have to first be exposed to the virus. You are exposed by coming into contact with respiratory droplets containing viral particles. The viral particles enter your body through mucus membranes like your nose, mouth, and eyes. We know close contact with infectious respiratory droplets is still the most common way to be exposed. Close contact is described as within six feet which is approximately the distance that large respiratory droplets travel before dropping to the ground or other surfaces. The virus can be carried in much smaller droplets called aerosols that travel farther distances and hang in the air longer. So is it airborne? There is a lot of debate going on in the science and health care world about this very topic and I'm not going to pretend like I completely understand it. Viral particles travel in respiratory droplets. Large respiratory droplets hold more viral particles than small ones. Large droplets fall to the ground (or other surfaces) faster than small ones; that's just physics. Small droplets are suspended in the air and can travel farther distances. They also dry out faster, leaving the virus vulnerable. The fat coat will no longer protect the RNA inside and once exposed, the RNA starts to break down. In terms of infectious diseases, airborne refers to the route of transmission. Not just that the virus is in the air but is it infectious. Can it cause infection? 

Documented cases of airborne transmission have occurred under specific circumstances. Studies of these transmission events have concluded that airborne transmission is more likely to occur in situations involving enclosed spaces, spaces with poor ventilation, and instances of prolonged exposure to respiratory droplets. Like choir practice, exercise class in a room at the gym, or spending time with family in a poorly ventilated home. In looking at how SARS-CoV-2 has spread in these specific settings and also generally, evidence still supports that the majority of transmission is by large droplets. Masks, distance, and handwashing are still the best ways slow the spread of the virus.

Reflecting back to early on in the pandemic, I didn't think we should all wear masks. When we only had the options of surgical masks and N95s, I discouraged people from trying to purchase them for fear that our health care workers wouldn't have enough. I was worried that even if they had masks, people wouldn't wear them correctly and would inadvertently infect themselves. I know I'm not wrong about that because I see y'all out there in the grocery store with your nose hanging out of your mask. 

Left side is a drawing of man's face with a mask over his mouth and his nose hanging out over the mask. The right sight is a drawing of a man wearing underwear with his penis hanging out over the top of the underwear. The caption reads "Wearing your face mask like like wearing your underwear like this."

Come on. Your nose is part of your respiratory system and you gotta cover that up. Nobody wants to see your nose. In terms of availability of masks, I could never have imagined all the Etsy shops, sewing circles, and small and large businesses that got into the mask-making game. I was flabbergasted. Many research studies have been conducted to learn more about how masks can help keep our large respiratory droplets closer to us and away from others. This is referred to as source control. Surgical-type masks, double or triple layer cloth masks, and other layered face coverings work by trapping larger respiratory droplets that may contain lots of virus. Masks that work for infection control are the kind like N95 masks. They must fit properly so that they create a seal around your nose and mouth and are made of material that filters out very tiny particles. Those are the kinds of masks that should be worn by health care workers who are treating patients with COVID-19. Your cloth mask can somewhat help keep you from becoming infected by trapping large droplets that you may come into contact with when you're close to someone who is infected. Masks aren't magical, they're just one part of how we can prevent transmission. Keep distance and wash your hands frequently too!

Keep it up, Minnesota! 1. Wash your hands. 2. Get tested when sick. 3. Stay six feet from others. 4. Wear a mask. 5. Stay home when able. 6. Work from home when able.

Alright, back to the learning. You can be exposed to SARS-CoV-2 virus, but not become infected. Suppose a small amount of virus gets into your body and either cannot find any ACE2 receptors or is trapped in the mucus and hair in your nose or are spotted immediately by an alert immune cell and are killed. No infection.

Now let's say the viral particles did find ACE2 receptors and have entered at least some of your body's cells. Your cells are infected! You can be infected and not have any symptoms of the disease COVID-19; you don't feel sick. This is referred to as asymptomatic infection, or without symptoms. The virus is being replicated in your cells, but your body is not sending out alerts to raise your temperature or cause inflammation. Understand that asymptomatic is in the eye of the beholder. This is often determined by asking someone if they have symptoms or had symptoms. Humans are notoriously really bad at doing health self-assessments. Do you remember how you felt three days ago? I don't. I can barely remember what I felt like an hour ago. There's also the caveat that many people who are not feeling any symptoms at the time of testing actually do go on to feel sick a day or three later. If nobody follows up with them, we never know that they did have symptoms. In some studies, these individuals are included in the overall asymptomatic number when they were actually presymptomatic, meaning they tested positive before symptoms started. People who are asymptomatic or presymptomatic are likely major drivers of transmission during the pandemic because they feel fine and go to work or hang out with friends or go to the gym all the while spreading a lot of virus around, unknowingly. Asymptomatic and presymptomatic infections are why we ask you to wear a mask and keep distance even if you're feeling fine.


If you have been exposed to and infected by the virus, you may come down with symptoms of COVID-19. It can take two days up to two weeks after being exposed before you begin to feel sick, but most symptoms start around day 4 or 5. The viral particles have taken over many cells in your body and your immune system has mounted a defense. A lot of symptoms of illness are actually related to the fight against the virus, symptoms like fever, body aches, and tiredness. Other symptoms come about because of the cell damage caused by the virus. If the virus has infected certain cells in your neurological system, you may lose your sense of taste and smell. Still other virus infects the cells of your blood vessels and you may develop clots that can lead to stroke or your heart may begin to malfunction. Remember earlier when I said that ACE2 receptors are found on nearly every cell type in your body? This is why people with COVID-19 can have cold-like symptoms, sore throat, brain fog, gastrointestinal problems, among many other symptoms. We know now that a significant proportion of individuals with COVID-19 remain symptomatic for months afterward. Their symptoms may wax and wane leaving them devastated thinking things are finally getting better only to be knocked down by persistent recurring fevers, fatigue, and heart palpitations a month later. This virus can cause serious lung damage and we don't yet know if people's lungs will fully recover or if they will have a lifetime of chronic illness. Consider that several studies have put the percentage of so-called "long COVID" at around 20-30% of cases. In the United States we've had a little over 30 million documented cases. That translates to approximately 6-9 million people with long-term symptoms. Some of them may have permanent damage to their lungs or heart. The devastation this virus is causing is immeasurable.

In the U.S. approximately 15% of cases are hospitalized. Maybe you feel more tired and run down than normal. You've got a fever and body aches; you have a cough and feel a little sick to your stomach. Shortness of breath starts a week later, but you try to soldier on. A few days after that you're in full blown respiratory distress and being admitted to the hospital. If you make it out, you'll be there for 10-13 days. Six percent of hospitalized patients are admitted to the ICU. People can have strokes; their organs may start to fail. 

Healthy, younger people who become infected and don't get very sick spread the virus around. An increase in cases leads to increased transmission. Hospitalizations and deaths follow, primarily in the older population and those with underlying medical conditions like high blood pressure and diabetes. When we look at hospitalizations by age, people aged 18-49 make up 30-40% of hospitalized patients. This is not a benign illness that only seriously impacts the elderly and you just don't know how your body is going to react to the infection.

How the vaccines work.

Now that we know what the virus looks like and how it can enter our body and infect our cells, let's learn about vaccines. Vaccines are a way to expose your body's immune system to a virus, bacterium, or parasite without you having to become infected and get sick. There are many ways that vaccines can do this. Each of the three COVID-19 vaccines currently available in the United States provide your immune cells with genetic information about how to make the spike proteins of SARS-CoV-2. Remember that the spike proteins are on the outer layer of the virus' coat and they are what allow it to attach to receptors on your cells and get inside. The vaccines differ in how that information gets to your immune cells. 

The Moderna-NIAID and Pfizer-BioNTech vaccines are mRNA, or messenger RNA, vaccines. The mRNA in the vaccines is a blueprint for making a part of the spike protein of SARS-CoV-2. Remember that the spike protein is the part of the virus that attaches to ACE2 receptors on human cells. The mRNA in the vaccine only has information for making those spike protein parts, not for making the actual virus. Now, mRNA can’t travel around your body on its own, it would basically just disappear in a puff of smoke like the Wicked Witch. Or maybe it would fade away like Marty McFly does in that picture. Yes, I’m making old references. Yes, I’m old. Deal with it. Both the Moderna and Pfizer vaccines use a nanolipid to transport the mRNA around. Nanolipid is just a fancy way of saying teeny, tiny fat droplet. The nanolipid keeps the mRNA safe from being broken down by enzymes in your body and allows the mRNA to enter certain kinds of cells in the lymph nodes nearest the vaccination site. These cells are called antigen-presenting cells, or APCs. An antigen is a substance that is typically not found in the body and is, therefore, recognized by the immune system as something that needs to be removed, destroyed, or vanquished. See also my body's absolute panic at finding the same dust mite poop that it's always exposed to. "What is this???!!! We must get rid of it!! Fire the sneeze machine! Send it out in a waterfall from the face ports! Get it OUT!!!!" Or something like that, I imagine.

A cartoon with four scenes titled Life with Allergies: Dust. Square one: A cartoon person pulls a book from the top shelf of a bookcase. The person says This book looks interesting. Square two: Dust flies out from the bookshelf towards the person. The person says Oh. Square three: Dust is getting into the person's eyes and mouth and the person says Oh no. Square four: A close up of the person's face covered in dust with tears streaming from their eyes. The person says Haha I guess I'll cancel all my plans for the next several days.

Once inside an APC called a dendritic cell, the nanolipid layer is broken down and the mRNA floats around in the cell cytoplasm until it runs into a ribosome. Sound familiar? Let's hold that thought and talk a little about the third vaccine.

The Johnson & Johnson-Janssen (J&J) vaccine uses a different delivery method than the nanolipid-mRNA system. It's called a viral vector, which means the genetic information needed to make the spike proteins is brought into your body by another virus. Scientists have done a bunch of science stuff to a virus called adenovirus type 26 to 1) make sure it won't make you sick and 2) give it the blueprints for making SARS-CoV-2 spike proteins. This time, the blueprints are added into the DNA of the adenovirus vector delivery system. Adenoviruses are common and cause illnesses such as colds, diarrhea, and pink eye. This particular one, type 26, is not commonly found in humans. This is important because it's highly unlikely that you have already been exposed to this adenovirus. If you had, and already have antibodies against it, your body would neutralize the virus vector and it would be unable to do its job. Again, highly unlikely. The adenovirus vector contains the information needed to produce SARS-CoV-2 spike proteins in its DNA. Once inside your body, the adenovirus binds to your cells, enters those cells, and releases the DNA. That DNA is then read and transcribed into mRNA by some of the nifty little gadgets inside of your cells. What happens next in terms of immune response is the same for all three vaccines. 

We return to the show to find our hero mRNA floating around the immune cell cytoplasm when suddenly it bumps into a ribosome!

A red and blue explosion shape with BAM! in the middle.

The ribosome reads the mRNA strand and makes the antigen part of the spike protein. After that, the mRNA is broken down. Basically a "burn after reading" spy situation. So now the dendritic antigen-presenting cell (APC) has these spike protein antigens and it does two things. 1) It presents the spike protein antigen by bringing it to its cell surface so that it can be seen and 2) It sends the spike protein antigens out of the cell using what's called the Golgi apparatus. The antigens presented on the dendritic cell surface entice immune cells called cytotoxic T-cells to come take a look. Think of a pie on a windowsill. A light breeze blows the scent of flaky, buttery crust and warm apple and cinnamon right under the nose of a Yogi Bear T-cell. The cytotoxic T-cells, also called CD8+ T-cells, are drawn over, bind to the substance that has presented the antigen on the dendritic cell's surface, and then kill the cell. This is called cell-mediated immunity. Cytotoxic T-cells go around the body looking for other cells with spike protein antigens and kills them.

The spike protein antigens that were shuttled out of the cell by the Golgi apparatus float around until they are taken up by another type of APC called a macrophage. Once inside the macrophage, the antigens are broken up and presented on its cell surface using a slightly different substance than was used by the dendritic cells. This substance entices a different kind of immune cell called a helper T-cell. These T-cells, also called CD4+ T-cells, send out a signal to call over yet another kind of immune cell called a B-cell. B-cells are the ones that create antibodies. Therefore, this type of immune response is called antibody-mediated immunity. The B-cells bind to the antigen and then split off into a clone of sorts called a plasma cell with the aid of the helper T-cells. Plasma cells make a counter substance to the antigen called an antibody, and they make a lot of them. Millions of them, and rapidly. Antibodies bind to the antigens in such a way that the spike proteins cannot then bind to your cell. The antibodies also mark that cell for destruction. Artist's rendition poorly drawn by me.

Drawing of two antigen presenting cells. One presenting the antigen to a CD8-positive T cell. The other presenting to CD4-positive T cell and a B cell. Plasma cells with y-shaped antibodies around them are also seen in the image.

Your immune cells that have encountered the SARS-CoV-2 spike protein antigen (made from information provided by the mRNA or adenovirus vector vaccines) are now prepared to locate and kill any cells that have that spike protein! In addition, these immune cells will continue to create antibodies that will bind to SARS-CoV-2 viral cells and prevent them from entering your cells, marking them for death.

All of this to say that it's way more complicated than that and you could just watch this hilarious, dramatic, and informative TikTok and go about your day.

One more thing on immunity. There are memory T-cells and memory B-cells that will remember the spike protein antigen if ever encountered again. This allows for a faster, more robust response. 

A couple more things about the vaccines. The mRNA from the Moderna and Pfizer vaccines does not enter the nucleus of your cells. The DNA from the J&J vaccine does enter the nucleus, but adenoviruses don't have the ability to integrate their DNA with the host. Neither the mRNA nor the DNA are able to change your genetic code. Full stop. Nanolipids are not tiny pieces of technology that contain microchips, they are just little tiny particles that don't dissolve in water (like oil) and act as a protective coat around the mRNA.

But what about immunity from natural infection, isn't that better than from a vaccine? It is true the most robust immune response is going to be from becoming infected with SARS-CoV-2. Your body's immune cells go through the same processes recognizing antigens and making antibodies as they do because of the vaccine. However, what comes along with infection is disease, cell damage in your organs, long-term symptoms, and possibly hospitalization and death. Infections also lead to school closures, cancellation of concerts and sporting events, closed bars and restaurants, among many other consequences. The risks of infection far outweigh the risks of vaccination.

Let's talk side effects. There are local side effects at the injection site. Most common are pain, swelling, and redness. I would describe the pain as a deep bruise, but it doesn't last for more than a few days. Less common but still totally normal is itching and rash. Then there are side effects that you feel throughout your body. These symptoms are related to your body doing the work of mounting an immune response. Most common are body aches, tiredness, headache, fever, chills, and nausea. You may have one or more of these symptoms and they may disrupt your life for a day or two. From personal experience after my first Moderna shot, I had a sore arm for a day or two. After the second shot, I had body aches, tiredness, a barely elevated temperature, and my arm was more sore. The symptoms started about 18-24 hours after the shot and were mostly gone later that night and the area around the injection site was just a little itchy. You'll be asked to wait 15 minutes after getting the shot before you leave just in case you have an allergic reaction. If you have had a severe allergic reaction to anything in the past, especially to any of vaccine components, be sure to tell the health care worker giving you the vaccine. They might ask that you wait 30 minutes.

You can find out if you're allergic to anything in the vaccine by checking out the ingredient lists which are publicly available on fact sheets.

Picture of a ball pit filled with blue, red, yellow, and green plastic balls. The words of above the photo read: If you've ever played in a ball pit at Chuck E. Cheese don't worry about what's in the vaccine.

Pfizer: mRNA, lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose.

Moderna: mRNA, lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose.

Johnson & Johnson: adenovirus particles and the following inactive ingredients: citric acid monohydrate, trisodium citrate dihydrate, ethanol, 2-hydroxypropyl-β-cyclodextrin (HBCD), polysorbate-80, sodium chloride. Each dose may also contain residual amounts of host cell proteins and/or host cell DNA.

Don't be intimidated by all of the numbers and long words! For example, the chemical name of table salt, NaCl, is sodium chloride. Besides the mRNA for Pfizer and Moderna, and the virus particles for J&J the other ingredients are there to maintain a specific pH level and preserve the environment so that the active parts don't degrade and become useless.

Lipids: carry the mRNA; not water soluble; lubricant

Salts: potassium chloride, monobasic potassium phosphate, sodium chloride, sodium acetate, dibasic sodium phosphate dihydrate, trisodium citrate dihydrate

Sugar: sucrose

Acids: citric acid monohydrate, acetic acid

Acid stabilizers: tromethamine, tromethamine hydrochloride 

Alcohol: ethanol

Emulsifier: polysorbate-80

Improves solubility: 2-hydroxypropyl-β-cyclodextrin (HBCD)

When you get vaccinated you can help keep track of side effects and help gain understanding of the vaccines' ability to protect against infection by participating in V-safe. V-safe is the CDC's smartphone-based after-vaccination health tracker. After you sign up, the tool will send you texts daily for a week after your vaccination asking about any symptoms you might be having. Then it sends a weekly text for 5 weeks asking about any symptoms and if you've had a positive COVID-19 test result. It will also send you a reminder for your second shot, if the vaccine you got the first time requires that. It's super easy and helps us all gain knowledge about the vaccines.

Each vaccine has a schedule too. The Pfizer vaccine is two shots 21 days apart; Moderna is two shots 28 days apart; J&J is one shot. These schedules are based on findings from the clinical trials for each vaccine, when the best immune response occurs.

Vaccine efficacy and variants.

If you've been paying attention to news media lately, you've been hearing a lot about viral variants and vaccine efficacy. What does it all mean?

Let's start with the variants. Every time the viral RNA is replicated, there is a chance that a change will occur. This change is called a mutation, and mutations occur all the time at random. A mutation can be just a single difference in the viral RNA strand. Remember that RNA is single strand of genetic information. On a closer level, the RNA strand is series of smaller segments called genes, which encode all of the parts that make a virion (spike, fat coat, RNA). What effect can a mutation have on the virus? Mutations can be beneficial, detrimental, or neutral. A change may make the virus more fit, less fit, or have no effect. Mutations are replicated and those that have a beneficial effect on the virus' structure make more virus with that mutation.

The variants that you've been hearing about in the news are classified as variants of concern, or VOCs. VOCs are so-called because the mutation or mutations that occurred have made that virus more fit. A mutation occurred that resulted in the spike protein having a higher affinity for the ACE2 receptor, meaning it can latch on more easily. The variant viral particles will be able to infect more of your body's cells and replicate so that there will be higher numbers of the variant than of the wild type. As you breathe, talk, sing, cough, or sneeze you will be expelling more of the variant virus. That's how the variants can become the dominant strain in your body and in the community. And the more virus circulating around, the more likely we are to encounter variants. If someone who has been vaccinated becomes infected, the virus in their body is likely to mutate in order to avoid being tagged by antibodies. Survival of the fittest and all that. While the virus is widely circulating, we're asking that people who are vaccinated continue to wear masks and maintain social distance in part to reduce the chances of creating even more variants. 

All the available COVID-19 vaccines have advantages and disadvantages, and they all have varying levels of efficacy. We can't directly compare any of the vaccines to each other to determine which is "best" or most effective. There are too many factors that differ; from the delivery methods to when the research trials occurred to what the primary endpoints of the trails were. Endpoints are the outcomes or goals of research trials. Primary endpoints varied. For example, one manufacturer's primary endpoint was protection of symptomatic infection 7 days after second dose and another's was protection against moderate to severe infection at 14 and 28 days after one dose. These goals are similar, but different enough so that we can't directly compare the results to each other. Some vaccine manufacturers had completed research trials before the emergence of virus variants that have differences in the spike protein. If the vaccine contains information to make a specific version of the spike protein, how well does it protect against a virus with a slightly different spike?

Emergency use authorization and vaccine safety.

You may have concerns about getting a COVID-19 vaccine because they have not been fully approved by the Food and Drug Administration (FDA) here in the U.S., or whichever group approves vaccines in your country. Completely understandable. Let's talk about emergency use authorization, or EUA. Emergency use authorization allows the FDA to preliminarily approve a medical device, medication, laboratory test, or vaccine for use to diagnose, treat, or prevent a life-threatening disease or condition. EUA can be given during public health emergencies and in situations of compassionate care. The product must meet a set of stringent criteria before an EUA may be given. This page on the FDA website gives a more in-depth explanation of the process.

The vaccine manufacturers with EUA for their vaccines have been able to show that the benefits of the vaccine outweigh any known or possible risks and that the primary endpoints of preventing severe disease and death from COVID-19 are met. The vaccines have been shown to be safe and effective and there is an expectation from FDA that the manufacturers continue to monitor trial participants. 

I wanted to understand more about how we have vaccines available in less than one year when normally it can take many years to get a vaccine from concept to approval. Turns out there are a lot of factors involved, not the least of which are collaboration, use of previous knowledge and technology, and money. Researchers can spend a long time in what's called the preclinical phase pouring over journal articles, experimenting with the virus to learn about its parts, and trying out different combinations to induce immune response in mice or other research animals. That's just to figure out the best possible options for the vaccine and it can take years. In the case of SARS-CoV-2, researchers from all over the world worked together to map out the virus and all its various parts and to determine the best potentials for vaccines. Another time-consuming part of the vaccine development process is finding the right delivery method and dose. Research into adenovirus vector technology has been ongoing for decades and J&J had already used adenovirus type 26 in its successful Ebola vaccine. The Pfizer and Moderna vaccines are the first of their kind, but research into using mRNA in vaccines started 30 years ago. Researchers had already done most of the heavy lifting when SARS-CoV-2 came onto the scene. The U.S. government gave a lot of money to pharmaceutical companies to pay for the research. When researchers don't have to spend the majority of their time writing grant proposals and worrying about how to keep the lights on, they are better able to do the actual sciencing. 

The vaccine trial process was also accelerated by combining trial phases that would under normal circumstances be separate. This allowed for checking vaccine safety and efficacy outcomes in parallel rather than sequentially. The manufacturers also enrolled more people in their phase 3 trials in order to have a more robust study. More people in the study means there is increased likelihood of finding adverse events and also increases the power of the study to find differences between the vaccine group and the placebo group. 

I found these two articles to be informative and easy to understand.

We've cut down on the research time by years, and we have large groups of vaccinated people being studied. So, what are we missing? Follow-up time. How long does immunity last and how often will we need to be vaccinated? Transmissibility. If I'm vaccinated can I still spread the virus to others? Safety and efficacy among different groups. Pregnant people and children are participating in vaccine trials right now because they weren't included in the initial phase 3 studies. Efficacy of the vaccines against VOCs. Moderna and Pfizer clinical trials occurred prior to the emergence of variants. New variants have emerged since J&J and others went through their clinical trials. Each manufacturer is testing their vaccines against VOCs to determine if they still work and labs around the world are testing people who have been vaccinated to find so-called breakthrough infections. What we're doing in the lab is taking samples from vaccinated people who are SARS-CoV-2 positive and checking out that virus. By looking at the RNA strand of the virus, we can figure out if the person was infected by a variant that has changed enough to evade the antibodies created in response to the vaccine. If we start seeing that and a lot of it, vaccine manufacturers will have to go back to the drawing board, and you and I may need to get a booster shot to protect against that variant.  

There is no vaccine in existence that prevents you from being exposed to a microbe that can make you sick. They don't create an invisible barrier around your body. And there are no vaccines that are 100% effective at preventing COVID-19, so there will be fully vaccinated people who still get sick. However, the vaccines are extremely effective at preventing death and disease severe enough to require hospitalization. Early studies are showing that they can prevent most symptomatic illness. And a recent release in the Morbidity and Mortality Weekly Report shows some very promising results. Fully vaccinated health care workers, first responders, and other essential and frontline workers were 90% less likely to be infected with SARS-CoV-2 than their unvaccinated counterparts. The study participants had received Pfizer or Moderna mRNA vaccines. This study shows evidence that vaccination can prevent infection, not just moderate to severe disease.

But we need to get as many people vaccinated as possible as quickly as we can in order to get there. Otherwise, the virus will still be transmitting, replicating and mutating, and making people sick. Many places in the U.S. have loosened restrictions and we're now seeing case counts on the rise again after a brief plateau.

Chart of daily trends in number of COVID-19 cases in the United States.

How high the rise goes is up to us. Do your part by getting vaccinated when it's your turn. Until then keep wearing your masks, stay home if you are able, wash your hands frequently, get tested if you've been exposed or you feel sick, and answer the phone when contact tracers call you.

There is a ton of misinformation and disinformation out there about COVID-19, the vaccines, masks, and pretty much anything related to this pandemic. I urge you to be skeptical of anything that you read on social media and even some news outlets. Except me. You can trust me. 

One year after the pandemic was declared by the World Health Organization, there are several vaccines being administered worldwide. Millions of people are now protected from getting extremely sick and needing to be hospitalized. Millions of people's lives will be saved. That is absolutely amazing, and we should celebrate!

Gif of a vial of vaccine wearing a label that reads "Vaccine COVID-19." The vaccine vial has arms and legs and a little face. They are holding a sign that reads "Vaccines Save Lives." White hearts appear and disappear on the pink background.

Sunday, March 15, 2020

Pandemic! Not just a game for science nerds.

Unless you've been sequestered somewhere with no internet or newspapers or you've just awoke from a medically induced coma, you've heard there is a virus currently spreading across the planet. I'm adding my voice to the masses that are talking about it. But you love my stories. So, sit back and relax, I mean you're quarantined anyway right? Let me tell you a story about icebergs, exponential growth, flattening the curve, and what preparedness should really look like (hint: it doesn't include hoarding toilet paper). 

Before we dive in, let's learn a little bit. The virus that everybody is talking about right now is called SARS-CoV-2, or Severe Acute Respiratory Syndrome Coronavirus number 2. It causes an illness called COVID-19, or Coronavirus Disease 2019. SARS-CoV-2 and COVID-19 should not be referred to as "China Flu" or "Wuhan virus" or "Wu Flu." If the outlet you are getting your information from has used any of those terms, turn the channel or close your browser window; you are not receiving accurate, helpful COVID-19 information. 

Transmission electron microscope image of SARS-CoV-2; Credit: NIAID RML

There are a whole bunch of coronaviruses out there in the world that infect animals, including humans. There are now seven coronaviruses known to cause disease in humans. Four of them, called the endemic human coronaviruses, are among the viruses that cause the common cold. The other three, SARS-CoV (the first), MERS-CoV, and SARS-CoV-2 are considered highly pathogenic; they can cause severe illness and death. The highly pathogenic coronaviruses are most likely bat viruses that get passed to humans from a different animal. For SARS-CoV it was masked civet cats; for MERS-CoV it's dromedary camels. We're still determining the animal associated with SARS-CoV-2, but do we know the initial outbreak in Wuhan, China is heavily associated with live-animal markets.

The current outbreak of SARS-CoV-2 has been classified as a pandemic by the World Health Organization (WHO). A pandemic is an epidemic that has spread globally. The outbreak first emerged in late December 2019 when health care workers in Wuhan, China noted a marked increase in cases of pneumonia of unknown etiology. That is, pneumonia for which we don't know the cause. At 3:08pm CDT on March 15th, 2020 there are 162,687 cases of COVID-19 reported by cities, states, provinces, counties, and countries across the planet Earth. This is according to a dashboard created by the Johns Hopkins Centers for Systems Science and Engineering. This dashboard is interactive and just a lot of fun...if you're into that sort of thing. Which I am, a lot. The WHO also has a dashboard. What times we live in! Data nerds unite! 

Unfortunately, the COVID-19 numbers are just the tip the iceberg and since the reproductive number is greater than one in a naive population, we're seeing exponential growth. In some places the cumulative number of cases is doubling every day, but thankfully we can see that with measures such as social distancing and testing and isolation we have seen successes in slowing the spread. Okay, okay that was a lot of jargon. Let's learn what it all means.

Tip of the iceberg: 
The iceberg analogy is used frequently when discussing any disease, including infectious diseases. The tip of the iceberg reflects the cases we know about. They have tested positive or are highly suspicious due to illness contact with infected persons or from places where the transmission is occurring. The part of the iceberg we see above the water is much smaller in comparison to the part under the water. There are many people with COVID-19 that we don't know about. They are asymptomatic or have mild illness. Or they were very sick but didn't get tested due to lack of knowledge of care providers, lack of tests, lack of testing reagents, or stringent guidance for who should be tested early on and some places still using that guidance because the system is already overwhelmed.

Credit: Dr. Bhoj R Singh

Reproductive number:
In its purest form, the basic reproductive number (often written as R0 and spoken as R not, which is actually spelled "R naught," because the English language is ridiculous). Anyway. In its purest form, the basic reproductive number is the number of people that any one infected person can go on to infect over the life of their illness, assuming a population with no immunity. It's not necessarily a constant; it can change if the population develops immunity naturally or by vaccination. Or if public health measures slow the spread. During a pandemic like the one we are in now, an R-naught of greater than one means transmission is likely to occur and an R-naught less than one means transmission is less likely to occur. Current research suggests the R-naught for SARS-CoV-2 is greater than one and is, on average, between two and three. Each person with COVID-19 may infect 2-3 people over the course of their illness. Some will infect more; some will infect none.

Exponential growth:
Here's a quick and dirty explanation: case number increases by the number of itself, over time. 8, 16, 32, 64 rather than 4, 5, 6, 7, 8 which is linear. In an epidemic, an important figure related to this growth is called the epidemic doubling time; the time between the doubling of numbers, reported in days for COVID-19. The doubling time is a moving target and is reflective of the situation at any given time and in any given place. The doubling time in China right now is less than that outside of China; the outbreak in China is on the way down and most everywhere else is on the way up. Exponential growth is currently unfettered; it won't stop until everyone is infected, or we have prevention by vaccination or other means. Which brings us to the next point: flattening the curve, community mitigation, and social distancing.

Flattening the curve, community mitigation, and social distancing:
If we're all going to become infected with SARS-CoV-2, let's not all get sick at once. Can we agree? We (collectively as humans) do not have enough ventilators in the world for every person that needs one if they become severely ill with COVID-19 and for those who are already on ventilators due to influenza, cancer, trauma, lung fibrosis, and many other reasons. Let's use the example of panic-buying toilet paper. Each store has a pretty good stock of toilet paper in times of calm. You may have noted on occasion "Why on Earth are there two full rows of toilet paper at this store?" No? Just me? Okay, fine. Normally, even if say 10% of shoppers on any given day are buying toilet paper, there's plenty left on the shelves for the next day and up until the store can restock the shelves. But if 80% of shoppers buy toilet paper at the same time one day, the shelves will be bare, and the store will have to put out everything they have in the stock room. Then the next day, 80% of those shoppers buy toilet paper. Now the shelves are bare and there's nothing in the back. And I'm rationing the three rolls I have left and I had to buy a four pack of cubes of tissues instead the three pack of full packages I usually buy and allergy season has already started. You monsters! I digress. The same thing that will happen in our health care system if we all get sick at once. It's been estimated that around 15% of COVID-19 cases will have severe illness that requires hospitalization and 5% will need intensive care. A portion of the 80% with mild illness may also require hospitalization for pneumonia. We simply do not have enough beds, gloves, gowns, masks, ventilators, dialysis machines, etc. for everyone to get sick all at once. See the "Alert Kitty" below. Flattening the curve is not about making sure our numbers are low in total, it's about spreading them out over time. See the "Lazy Kitty." 

Credit: Dr. Anne Marie Darling

How do we become the lazy kitty? By community mitigation and social distancing. Communities should cancel all large gatherings such as parades, conferences, rallies, concerts, sporting events, schools, etc. You as an individual should avoid crowds, consider doing your grocery shopping online or go to the store when the parking lot is relatively empty. Avoid mass transit if possible or at least try to keep 6 feet between you and the people around you. Wash your hands often and always when you get home from being out in the world. Work from home if that's a possibility. Don't go to work or restaurants or grocery stores if you are sick, even with a cold. Keep your kids home if they are sick. Be a lazy kitty. Help out your elderly and disabled neighbors by offering to shop for them or set them up with a food delivery app if they have a smartphone or tablet. But don't you dare go over there if you are sick or have been exposed to COVID-19. This disease is very deadly for the elderly. Keep them safe.

What preparedness for COVID-19 should actually look like:
  • Make sure you have at least a two-week supply of your prescription and over the counter medications
  • Make sure you have a two-week supply of food and essentials like diapers and toilet paper. TWO WEEKS. Not a supply to last until the end of days. I don’t know how much toilet paper y’all go through in two weeks, but if it requires you to buy 72 rolls, I’m concerned.
  • Create a plan for your family in the event that your household is quarantined or curfews are enacted in your community. This is already happening in the U.S. Hoboken, New Jersey has instituted a curfew from 10pm to 5am, nightly.
And now we come to the portion of the program where we answer viewer questions. I asked my friends and family to give me their burning COVID-19 questions. I've tried to answer to the best of my abilities with the available information. Reminder that this virus is still very new and the answers I found now are subject to change as we learn more.

How long does illness with COVID-19 last? 
  • We don't know for sure. This is a new virus and researchers are working diligently to figure all of this out. 
  • This was the hardest one for me to find an answer for. I've looked at countless journal articles associated with the current outbreak, but almost none have data on time to recovery. What I did found out though is it turns out the "80% have mild illness" figure that we keep seeing out there includes mild pneumonia as well as what I would assume is actual mild illness. So, there's that. Definitely not just "the flu." 
  • I've seen data showing that if pneumonia develops, it's about a week after one starts to feel sick with cough and fever.
  • One case report of an individual with cough and fever who developed mild pneumonia around day 9 of illness that likely was only diagnosed because he was in the hospital (after testing positive, not because he was that sick). This is the first case reported in the U.S. He started to get better on around day 12, but at the time the article was released in late January, he was still hospitalized so we don't know exactly how long his illness lasted in total.
  • One case report of an individual sick with high fever, cough, and fatigue for three days and then recovered. This is a case in Germany that caught COVID-19 from an asymptomatic colleague. 
  • There is a report of 12-32 days from symptom onset to recovery. This is a tiny case study of four medical professionals who all developed mild pneumonia and were treated with antivirals.
  • I have seen modelling studies using a time to recovery of 21-22 days. These are studies that use available data to estimate how an epidemic will play out. And I do remember seeing this 21-day figure in an early report coming out of China, but I can't find the source again. It was looking at hospitalized patients and showed 21 days from onset to recovery and also 21 days from onset to death for those who died.
  • Bottom line: 
    • You'll be sicker longer if you develop pneumonia (be aware of difficulty breathing). 
    • Risk of severe illness requiring hospitalization or of death increases significantly with age over 60 or medical conditions like heart disease, high blood pressure, lung disease, cancer, diabetes, pregnancy (current or recent), kidney, or liver disease.
How long is an infected person contagious?
How does the virus spread (droplet vs airborne)?
  • All available evidence supports that the virus SARS-CoV-2 is spread person to person by respiratory droplets.
  • These respiratory droplets come out of your mouth and nose when you speak or sing or simply breathe and they hang out in the air a little while and then fall. When you sneeze or cough, you expel the droplets much farther. See this great Science Friday video of a sneeze! This is why we keep telling you to sneeze into your sleeve.

  • The virus does not appear to persist in the air like airborne viruses such as the virus that causes measles. That virus is also expelled when coughing or sneezing, but it can remain in the air for up to two hours in its infectious state. A person with measles may sneeze in an elevator and then leave. An hour later, an unvaccinated person enters the elevator and breathes. They are now infected and may go on to develop symptoms. An hour later! There isn't any evidence to support that the virus that causes COVID-19 is spread this way.  
  • Evidence does suggest, however, that the virus can be transmitted by touching inanimate objects or surfaces contaminated with SARS-CoV-2 and then touching your mouth, eyes, or nose.
How long does SARS-CoV-2 live on surfaces?
  • Researchers looked at available data for human coronaviruses (the ones that cause the common cold), the first SARS-CoV, MERS-CoV, and other similar animal viruses. What they found is that human coronaviruses can remain infectious on surfaces for up to 9 days. This varies widely depending on the type of surface (hard vs soft, glass vs metal) and other conditions such as humidity, temperature, and how much virus is present. 
  • These studies are done in laboratories where conditions can be controlled, which is not the case out in the real world.  
  • Don't panic! The studies also show that these viruses are readily removed from surfaces using appropriate disinfectants for the recommended amount of time. More on that next.
What about those wipes by the carts at Target and other stores?
  • Disinfectant wipes and sprays:
  • Check the label where it lists the bacteria, fungi, and viruses that it is active against. Look for human coronavirus or other similar viruses or viruses that are harder to kill than coronaviruses (like Norovirus and other calciviruses). 
  • The EPA has a wonderful list that you can check your product against.
    • Check the label for the EPA Registration number, or EPA Reg. No. and enter that number into the search bar. If your product shows up, it can be used to disinfect SARS-CoV-2. 
    • Follow the instructions for the virus listed in the EPA table and on the label of your product. There will be a specific contact time. This is the amount of time the surface must remain wet in order for disinfection to occur
    • Some products have a very long contact time which can be difficult to achieve. Others, the contact time may only be a few minutes. 
  • Wipes by the carts at Target and other stores:
    • Specifically the blue cart wipes at Target stores in Minnesota: I got lucky the other day at my Target in that I saw a roll of the blue wipes at an empty register waiting to be placed in the cart wipe container (that doesn't tell you what they are or how to use them). The active ingredient of those wipes is 0.12% benzalkonium chloride and that is not on the EPA list of disinfectants to use against SARS-CoV-2. 
    • At other stores or Target if the wipes aren’t blue, check to see if the wipe's product name is on the container. If so, search for it on the EPA website. If not, try to find a manager and ask for the name of the product or the EPA registration number.
    • Consider this though: Will you wait 4 minutes, ensuring the cart handrail remains wet for the whole 4 minutes, before going about your shopping? Did the person before you? Or behind you?  
    • I'm not saying don't use the wipes, they will clean off the boogers and potential fecal matter left by the toddler that was sitting there before you. But they're not really for true disinfection.
What of Africa and other places with low numbers? Why no spread of COVID-19?
  • Wait for it...
    • In Africa, there are outbreaks in South Africa and Algeria and five more countries reported cases on Saturday 3/14/2020
    • In the U.S., as of 4:00pm CDT on 3/15/2020 every state except West Virginia has reported at least one case.
    • Remember the iceberg analogy. 
  • Depending on the capacity to test (kits, reagents, trained personnel), it may be that only the sickest or highest risk or those with obvious links to known cases are being tested.
  • Low numbers do not necessarily mean that there aren’t any cases or that there isn’t any spread.
Why weren't we more prepared in the U.S.?
  • Funding for public health isn't usually a priority when there are so many programs competing for dollars. 
    • Research from the American Public Health Association shows national investment in public health capabilities needs to be around $32 per person and we are, as of October 2019, spending $19 per person.
    • State and local health departments are underfunded and often working with bare bones staffing; this includes public health laboratories.
  • State public health laboratories were required to use the CDC-developed assay and until those labs were up and running, only CDC was doing testing for the entire country.
    • Only those with strong epidemiological connections to the outbreak in China and symptoms of illness were being tested early on. 
    • This no doubt allowed COVID-19 to spread silently. Mild illness usually does not lead one to a doctor's office or hospital. 
    • The first roll out of the test kits included faulty reagents that set testing back by a couple of weeks.
  • Dr. Anthony Fauci said, "The system is not really geared to what we need right now. That's a failing. Let's admit it."
Can I get it from a dog? Do dogs or other pets get infected or spread COVID-19?
  • You may have heard of the dog in Hong Kong that tested positive for COVID-19. The dog's owner had COVID-19 and to be honest, I don't really know why the dog was tested. The original report is behind a paywall. All other reports I've read on veterinary sites state that the dog did not have symptoms of illness.
  • There is no current evidence to suggest that pets play an important role in the spread of COVID-19.
    • However, if you have COVID-19 the recommendation is that someone else care for your pet or service animal. 
    • If that isn't possible, then wash your hands before handling your pet or service animal and avoid snuggling and kissing. 
    • YEAH RIGHT. Sorry Maxdog, if I get COVID-19 you're coming down with me!
Maxdog aka Maxwell Copernicus aka the Best Chihuahua Ever

What am I doing to be safe at work and other places?
  • My coworkers and I in the public health lab and in laboratories all over the world take precautions every day, regardless of COVID-19 or any other infectious disease.
  • We wear gloves, lab coats, and eye protection when in the lab.
  • We only open direct patient samples in a biosafety cabinet that is working properly to keep the air inside the hood.
  • We wash our hands frequently while working in the lab and every time we leave the lab. 
  • I am washing my hands when I come home from being out in the world. I'm not currently doing much else different because, as an introvert, I've been social distancing my whole life! And I have allergies so not touching my face is just not an option. All kidding aside, I do have tickets to a drag show in a couple weeks and I'm keeping a close eye on how things play out. I will follow the guidance of the Minnesota Department of Health and the CDC.
Should I travel?
  • I can't answer this for you. You have to take a number of factors into account.
  • My advice is to pay attention to the CDC's travel website in general, and the COVID-19 page specifically. They have recommendations for international travel, cruises, frequently asked questions, and things to consider for travel within the U.S.
And last, but certainly not least:
Can I catch COVID-19 while having sex in a hot tub?
  • I know this was a cheeky question, but I'm answering it anyway!
  • Short answer: It depends! Does your partner have COVID-19? Then the answer is yes, you can catch COVID-19 while having sex in a hot tub. Sorry.
  • You're more likely to get "hot tub rash" though, which is a skin infection caused by Pseudomonas aeruginosa. Yuck.
Y'all. I think this is the longest post I've ever done! I mean, it is a pandemic after all, so I guess it's warranted. Let's recap a few key points, shall we?

1. SARS-CoV-2 is the virus that causes an illness called COVID-19.
2. COVID-19 has spread globally, and the WHO has officially called it a pandemic.
3. The virus spreads easily from person to person through close contact and also from touching contaminated surfaces and then touching your mouth, nose, or eyes.
4. Most people who catch COVID-19 will have fever and cough. Some people develop mild pneumonia. Others get very sick and need to be hospitalized. People are dying, particularly the elderly and those with medical conditions.
5. Older age or medical conditions such as heart disease, high blood pressure, lung disease, cancer, diabetes, pregnancy (current or recent), kidney, or liver disease significantly increases your risk of severe illness requiring hospitalization or of death.
6. Nationally and globally, our health care system cannot handle it if we all get sick at once, so we need to practice social distancing.
7. Check on your elderly and disabled neighbors.
8. Wash your hands.
9. Don't hoard toilet paper. Or cold medicine. Or bottled water. Or tissues.
10. Don't have sex in a hot tub. Unless it's your personal hot tub. That no one else ever uses. Then maybe.

Be safe out there. 
World Health Organization:
Centers for Disease Control and Prevention: