COVID-19

Vaccines: Testing Methods, Clinical trials, Denial Rhetoric

UPDATE: U.S. Pandemic Response in the Global Context

The following figure illustrates the U.S. in relation to the rest of the world. While only 4.5% of the global population, the U.S. currently accounts for 32% of new COVID-19 cases daily, and 16% of total deaths. That is 8 times the expected amount of new cases, and 4 times the amount of deaths that would be expected, especially in a "developed" nation. Why is such a huge proportion of this death and infection rate in the U.S.? I suspect it is a combination of the following: low vaccination rates, lifting of mask mandates, lack of universal healthcare, lack of testing and contact tracing, lack of lockdowns when community spread is high, and lack of a clear and unified apolitical message from healthcare and community leaders about the science, risks, and impact of COVID-19.

SARS-CoV-2, which stands for Severe Acute Respiratory Syndrome-Coronavirus-2, is a type of virus capable of infecting humans after contact with infected animal hosts, respiratory droplets, and from surfaces to human hosts (if environmental conditions are correct). The virus is also commonly called COVID-19, which stands for COrona VIrus Disease and -19 indicates the year 2019, referring to when the pathogen was first discovered. This group of viruses have previously infected human populations in the form of other respiratory diseases such as MERS and the common cold. Each individual piece of this virus, called a virion, is circular in shape with protein spikes that give this group of viruses the name 'corona' from the Latin word for crown. The genetic material is called RNA, and for this virus, the RNA is single stranded and positive sense. To learn more about this virus's structure, RNA genome, gene expression, and replication see here. To see images of the virus under a high-powered microscope, see this study. COVID-19 has spread rapidly through the world, and here in the US, over 300,000 have now died as a result of infection. Symptoms include one or multiple of the following: fever, chills, cough, difficulty breathing, fatigue, muscle and body aches, headache, loss of taste or smell, sore throat, nasal congestion, nausea, vomiting, and diarrhea. If you are reading this and experiencing any of these symptoms, please seek testing for COVID-19 and contact your primary care physician. If you are reading this and you or a loved one are experiencing additional, serious symptoms of trouble breathing, pressure or pain in the chest, confusion, inability to stay awake or wake up, or bluish lips or face, please immediately go to the emergency room for critical care.

Because of a lack of governmental guidelines to enforce and mandate quarantine measures when appropriate, prompt contact tracing and aid in isolation, mandatory masking when necessary, and social distancing as needed, we in the US now must rely on vaccination to reduce the spread of COVID-19, especially to those in groups most likely to suffer serious illness if infected. Many different efforts and groups are producing different types of vaccines for unique situations world wide. I will talk about the ones that have either gone through required clinical trials, and those that are on the path to approval or that have been approved here in the United States. I recently caught COVID-19, even after following all recommended precautions. Even though I am relatively young and healthy, I was very sick. I had fiery pain all throughout my torso and legs for five days which made any movement excruciating, fever, loss of taste and smell, and body fatigue. With community spread on the rise, especially in Tennessee, where I am, I am noticing a disturbing and increasing amount of incorrect and misleading information regarding this disease, social safety protocols, treatment procedures, and especially the vaccines that will be available soon. Even more concerning are emerging strains of COVID-19 that are even more contagious than the original strain. Below I attempt to summarize what is known in the scientific community so far, and evidence that alleviates concerns and dispels myths, especially about vaccination. Part of this is because I am fascinated by viruses--tiny bits of genetic material that hijack our own systems in order to replicate, and in part because I want to encourage vaccination to prevent further loss of life.

*I am not a medical doctor, nor have I conducted research on public health or human pathogens. My expertise and formal education is on plant pathogens and epidemiology, which has parallels but is not the same as human pathology or epidemiology. Below is my summary of what we is known about COVID as of January 2021, and links for you to read for yourself and provide for others. Always ask your doctor if you have questions or concerns about COVID-19 and follow the most up-to-date recommendations of public health officials to do your part in protecting the health and safety of our communities from this pandemic. For any of my clinical research friends and practicing MDs, your correction and criticism if I've gotten anything wrong is always appreciated!

TESTING METHODS

1. Antibody tests

Antibody tests are available to see if your immune system has antibodies, or proteins that help fight off infections, that are specific to the family of viruses that COVID-19 is a member of. Because it is not specific enough to determine if you have the specific COVID-19 virus, these tests are not adequate to determine whether you currently or previously have had COVID-19. Additionally, it takes a while to build up antibodies once you have been infected, so you may be infected with COVID-19, but if you take an antibody test too early in the infection process, the antibody test will not show that you have antibodies to the virus. For more information about antibody tests, including commercially available tests, see here.

2. PCR tests

The abbreviation PCR stands for Polymerase Chain Reaction. These tests amplify specific sections of nucleic acid. With COVID-19, RNA (ribonucleic acid~similar to DNA) is the nucleic acid that is amplified. These tests are much more sensitive and able to detect the specific COVID-19 virus. PCR is the method used to amplify nucleic acid for genetic sequencing, which is how we detect changes in the genetic structure of the virus. PCR tests can tell you if you have RNA from COVID-19 in you, however they cannot tell you if you are still shedding infective virions. Studies show that approximately 10 days after you begin to experience symptoms you are likely no longer shedding infectious COVID-19 particles. In fact, you may test positive for up to a month after a first positive diagnosis of COVID-19, which is why once you are no longer experiencing symptoms and it has been at least 10 days from a first positive test you can safely come out of self-quarantine.

PREVENTING SPREAD

1. Herd immunity

The concept of herd immunity is when a large enough percentage of the population have their immune systems trained to overcome a disease before becoming infectious and spreading the disease to others. This is exactly what vaccines do; train the immune system to overcome a specific pathogen to prevent it from causing severe symptoms and prevent it from reaching levels that can then be spread to another person. Another way to achieve herd immunity is by actual infection and survival of the disease by a large percent of the population. However, with a disease as deadly (1% death rate in the US population =3,280,000 deaths) and with as many long-term health consequences as COVID-19, it is not a moral choice when immunity without sickness is available in the form of safe, effective vaccination. Another unknown with COVID-19 at this time is how long immunity post infection lasts; although I contracted and recovered from COVID-19, I am unsure if my immune system will protect me from a subsequent infection for months or years. For more on past establishment of herd immunity, see here.

2. Mandatory masking

Unfortunately, mandatory masking is not currently a reality in many parts of the US even thought we are in the worst stage of the pandemic to date, and it is the consensus that mandatory masking helps reduce the spread of COVID-19, but only if done at a larger, population level to prevent community spread.

3. Social distancing

Without many effective therapeutic drug options and with a slow vaccine roll out in the US, social distancing and avoiding spending long periods of time with those you do not live with in an indoor setting is very important. A nice summary of the ethical and scientific basis of social distancing can be found here. Consistent messaging and policy from political leaders and science communicators going forward will always be important in effective social distancing policies.

4. Contact tracing

Contact tracing efforts vary by state. Here in Tennessee, I was not contacted by a contact tracer until 10 days after my positive test. This is an abysmally long time to check in on someone who might be extremely ill, who might live alone, and might have no means to support themselves during this time when so many have lost jobs and support systems. Stronger contact tracing efforts are desperately needed to reduce the spread of COVID-19 and make sure close contacts of those who test positive are quickly tested and self-quarantine. If you are interested in the modeling and importance of a short time interval between a positive test result and contact made by contact tracers, see here.

5. Case studies: when listening to scientists worked

One thing I have heard people say is "well it's bad everywhere" as an excuse to not criticize the inaction of politicians and policy makers in regards to instituting and enforcing things like mask mandates and better contact tracing. For example where I am, the governor has approved time and effort to go into prayer emails regarding COVID-19 instead of diverting as much time and effort into things that are proven to reduce transmission such as mask mandates and improved contact tracing (this is not a joke, unfortunately). Below are just a few examples of countries whose leaders reacted quickly and listened to the advice of epidemiologists, resulting in very low COVID-19 spread.

- Vietnam

Many factors including geographical proximity to China and having comparatively fewer resources than countries such as the US might lead one to believe COVID-19 would have been disastrous for Vietnam. However, this was very much not the case, with only 35 COVID-19 related deaths in a population of 98 million since the pandemic began. To read about how early actions by the government has allowed this to happen, this paper is an interesting read.

- New Zealand

New Zealand is a comparatively developed country, with a population of 4.9 million people and only 25 COVID-19 deaths since the beginning of the pandemic. A prompt and strict lockdown helped halt the spread of COVID-19 early on in its tracks in the country. To read more about New Zealand's management of COVID-19, see here.

DEMOGRAPHICS

"Of all the forms of inequality, injustice in health care is the most shocking and inhumane" -Reverend Martin Luther King Jr, March 1996, Convention of the Medical Committee for Human Rights

Similar to many other facets of American society, the impact of COVID-19 is felt more heavily by populations of color, notably Black, Latino, and Indigenous peoples, than it is white people. This impact is due to socioeconomic disparities in minority groups ability to attain things like health insurance, and racism faced within the healthcare system which create barriers to receiving critical care and justified mistrust in medical institutions. There are many myths that suppose why this is, and why medical racism persists, and for a nice summary of what has been done and ongoing work to fight medical racism, I recommend this read.

VACCINATIONS -

Photo ID: Chart of those that have gone Emergency Use Authorization (EAU) and those going through late-stage clinical trials as of December 2020.

Source here

Approved in the US

1. mRNA vaccines

mRNA stands for messenger ribonucleic acid. These vaccines do not have any pieces of the genome that is necessary for the virus to be alive and self-replicate. The bits of mRNA that are contained in the vaccine are from the outer protective layer of the individual virus particles that encode spikes made out of fats called lipids. Once injected, the human immune system reacts to fight off this new, foreign genetic material, and can recognize it when a full live virus particle enters the system. The immune system's conditioning via the vaccine gives the body a better chance to successfully fight off the virus best-case scenario, and at the least, a much more mild case occurs as opposed to hospitalization. Currently, best protection is achieved with these vaccines when given in two doses 21 days apart into the upper arm.

- Pfizer Ingredients:

• mRNA: bit of genetic code in the form of COVID-19 proteins from the spike protein layer of the virus (not the entire or active virus) to trigger the immune system to break down if exposed to live, infectious virus particles

• Lipids: a fancy word for fats. these help the mRNA more easily be delivered into the cytoplasm of the cells. The specific lipids in the Pfizer vaccine are: cholesterol, 1,2-Distearoyl-snglycero-3- phosphocholine (PubChem), (2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (PubChem), 1,2-Distearoyl-sn glycero-3- phosphocholine (PubChem), and cholesterol (PubChem)

• Salts: maintain acidity with vaccine delivery. The Pfizer salts include potassium chloride (PubChem), monobasic potassium phosphate (PubChem), sodium chloride (PubChem), dibasic sodium phosphate dihydrate (PubChem)

• Sugar: sucrose is included in the vaccine to help preserve the integrity of vaccine ingredients in cold storage (PubChem)

- Moderna Ingredients:

• mRNA: bit of genetic code in the form of COVID-19 proteins from the spike protein layer of the virus (not the entire or active virus) to trigger the immune system to break down if exposed to live, infectious virus particles

• Lipids: the lipids in the Moderna vaccine are SM-102 (lipid synthesized and details proprietary to Moderna), 1,2-dimyristoyl-rac-glycero3-methoxypolyethylene glycol-2000 [PEG2000-DMG] (PubChem), 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC](PubChem), and cholersterol (PubChem).

• Stabilizers: the following aid in ensuring vaccine stability and integrity once it has been produced: acetic acid (PubChem), acid stabilizer tromethamine (PubChem) and acid stabilizer tromethamine hydrochloride (PubChem), sodium acetate (salt) (PubChem), sucrose (sugar) (PubChem)

- Allergic Reactions

Pfizer & Moderna vaccines

Allergic reactions have been documented after taking the first dose of the Pfizer vaccine. The reactions, for the most part, have occurred in patients with a history of allergic reactions, and serious anaphylaxis reactions, for the most part, have occurred within 15 to 30 minutes of receiving the vaccine, a short enough window to allow treatment of the reaction. Other, extremely mild reactions to the vaccine include the urge to scratch the skin, rash, itchy and scratchy sensations in the throat, and mild respiratory symptoms. If you have a history of anaphylactic-type allergic reactions, sticking around for a little while to monitor your health may be a good idea. For more on allergic reactions and suspected cause of reaction after first injection of the Pfizer and Moderna vaccines, see here and here.

CONSPIRACY THEORIES

- Autism and Vaccines

For a thorough, well explained and quick summary of how the myth of vaccinations being the cause of autism, I recommend reading this article here. Currently, it is thought that mutations in several genes during the period of pregnancy are correlated most strongly with autism. These mutations can cause hyperconnectivity of neurons, and interference with amino acid transport to the brain. Multiple other genetic factors may be at play in autism and these are currently the subject of extensive study. It is firmly debunked that vaccines cause autism, and no evidence suggests that any available COVID-19 vaccines correlate to autism.

- 5G

Recently in my hometown of Nashville a domestic terrorist detonated a bomb downtown near the AT&T building (a company closely involved with the roll out of 5G technology), making it likely that he was incorrectly thinking that he was protecting people from the "dangers" of 5G. Some fringe movement that are now percolating into the collective consciousness now even consider 5G to be the cause of COVID-19 and many other ailments. This is quackery at its finest and has no basis in reality or rigorous scientific inquiry. I won't even share the "papers" here that have been published on the subject. But this is an opportunity to say that just because you find a paper in a journal that appears "scientific" and claims to be "peer reviewed" or that you find on a search engine...it does not mean it has actually gone through the rigorous peer review process. See here for a list of potential predatory journals. These journals sound like they're legit, but often charge high fees to publish quite literally anything. If you're ever suspicious about what you read, it's always a good idea to double-check it has been published in a reputable journal.

For a summary of the most common conspiracy theories in regards to COVID-19 from the Genetic Literacy Project, see here.

STAYING INFORMED

Social media

Below are some accounts/resources I recommend following for updates on COVID-19 and information in general about the pandemic.

Twitter

@PeterHotez - Dr. Peter Hotez, MD, PhD is a vaccine developer for neglected tropical diseases, and author of many books that I recommend sending to any friends/family experiencing vaccine hesitancy

@DrTomFrieden - Dr. Tom Frieden, former Director of the US Center for Disease Control & Prevention. He provides lots of up-to-date information about the science of COVID-19 as it unfurls in real time, along with resources to studies on emerging issues re: COVID-19. His weekly blog is also very informative: https://www.tomfriedenpublichealth.net/tom-frieden-blog

** @JamesEKHildreth - Dr. James Hildreth, MD, PhD is the president of Meharry Medical College in Nashville, TN. He is an HIV/AIDS prevention and treatment specialist and researcher. He played and continues to play a key role in approval of vaccines for emergency use in the US and does an excellent job of science communication via Twitter

Podcasts

Talking Biotech Podcast - Dr. Kevin Folta talks about emerging biotechnology in medicine and agriculture. Many recent pods delve into the science behind mRNA vaccines and the COVID-19 pandemic

The Antigen Podcast - produced by Pfizer, creator of an mRNA COVID-19 vaccine, this podcast describes the origins of vaccination from the very first, rudimentary kind to the process of developing COVID-19 vaccines. An informative series

America Dissected: Coronavirus - Dr. Abdul El-Sayed discusses many relevant issues in regards to COVID-19 in America. The diversity of topics is very informative and interdisciplinary

PERSONAL RESPONSIBILITY

Knowing what we know, we all have a personal responsibility to protect not only our own health, but the health of our vulnerable community members. Everything we do when we come into contact with each other has an inherent amount of risk, and we all know what we can do to reduce that risk. We can remain 6 feet apart. We can wear a mask indoors and outdoors when around others who we do not live with. We can choose not to put ourselves into enclosed, uncirculated air space like gyms, studios, etc. because we are more likely to transmit and contract COVID-19 in those spaces. And we are aware of the social justice impact of that choice on communities of color, persons with preexisting conditions, and the elderly. The choice to be in those spaces has inherent unjust implications at this time. There is no other way to put it. Sure, you may be young and healthy and lucky enough to recover from COVID-19 like me, but the person you unknowingly infect while unknowingly contagious most certainly might not be. Or might be fired from their one source of income because they get sick. I am personally very upset to see friends and acquaintances of mine, especially those with varying amounts of medical training, traveling domestically and internationally at this time. I expect more from you and community care and public health is more important than a vacation right now, no matter how cheap flights are. Now is a time to put aside the myth of individualism. What we do now in the coming months is going to have an real and lasting impact on our communities and the best thing we can all do is stay home, wash our hands, and stay masked up as much as possible.