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  • Dr. Elizabeth O'Day

The Simple Science Behind the COVID-19 Vaccine

When it comes to concerns over COVID and the vaccine, it feels like we are talking past each other. This is not only unproductive but potentially dangerous. This letter to a fictitious uncle Shawn from my 3-month old is my attempt to provide simplified information on the science (both what is known and what is not known) so that individuals can be more confident in their decisions.


Dear Uncle Shawn,


I’m sorry to hear you won’t be able to attend the party. Mom told me it’s because you are unvaccinated, and she doesn’t feel comfortable having you over because I’m not old enough to be protected by the vaccine. When I asked her why she explained to me how the disease spreads and how the vaccine works. I want to make sure you know all the details too.


First, COVID-19 is a disease caused by a virus known as SARS-CoV-2 (1). It’s an RNA virus which means that when it enters your body, it takes control of your body’s protein machinery. This allows the virus to start making viral proteins and ultimately more virus. The newly made viral proteins and RNA form viral particles that leave one infected cell and go on to infect more cells (2). And because the infected cells just make more virus, they don’t keep up with their normal activities to keep us healthy, and people get sick. COVID symptoms (3) usually start with a dry cough because at first, the virus is just messing with the cells in your throat, but it can quickly travel to the lungs causing difficulty breathing and then multiply throughout your body (4).


At some point, your immune system realizes the viral particles are bad, so it tries to kill all the infected cells. But it’s tricky because if the virus has spread to too many cells, our immune system can actually make things worse by causing widespread damage (5). And unfortunately, there are no proven treatments for COVID, so you must wait and hope that your immune system clears the infection before things get bad (6–8).


The vaccine works to prevent severe cases of COVID, keep you out of the hospital, and keep you alive. The Pfizer and Moderna vaccines are made from mRNA. mRNA stands for “messenger RNA” and it functions as a way for specific cells to only express certain genes. mRNAs get turned into proteins that carry out cellular activity. When you are given an mRNA vaccine (9) it enters your cell, and it uses our body’s protein machinery to make the protein encoded in the mRNA sequence. The J&J vaccine is a little different, in that it is a DNA vaccine. But it works in a similar fashion, it enters your cells and uses normal cell machinery to first be turned into mRNA and then into a protein. The code embedded in all vaccines contains instructions to make just one thing- a part of a viral protein called the spike protein (10). Since your body only makes this one protein, the vaccine can’t infect your cells in the same way as the real virus. Also, even though the vaccines contain mRNA or DNA they don’t do anything to our own DNA. Altering our own genome is known as gene editing (11) and honestly, it’s quite tough to do. Scientists are trying to develop ways to do this to treat genetic diseases, but it requires a lot more stuff.


Mom explained to me how the vaccine offers protection. The vaccine makes your cells produce the spike protein, which the immune system notices is not a normal human protein, so it produces antibodies against it. Then if a real viral particle enters your body, your immune system already has antibodies to quickly recognize it and get rid of it (12). Some breakthrough infections are expected but usually, those cases are less severe (13) because the immune system has some antibody pool to draw on.


Right now the vaccines are more than 90% effective, which means if nearly everyone got it, we could be rid of the virus (14,15)! Remember viruses need to infect a human to survive. And the other thing to know about viruses is that they are constantly mutating (16). You see every time the virus infects someone it can slightly change (this is what the delta variant is). So, this could be mean that antibodies from the current vaccine may not recognize a new mutated spike protein as well or at all. This is in part why we will need boosters in the short term and if things get worse, we will even need new vaccines! I think this is why so many folks are frustrated that people won’t get vaccinated because if they did, the math suggests we could be done with all of this but if the virus mutates, we may lose the chance!


Mom said some people were concerned that the vaccine didn’t have full FDA approval, but that’s happened now! The vaccines have been given to millions of people and there have been very few adverse reactions (17). For example, there was a lot of news that the vaccine has a risk of heart problem called “thrombosis with thrombocytopenia syndrome (TTS)”. But in the US, for the J&J vaccine, only 44 cases have been confirmed and there have been more than 14 million doses of the vaccine given (that’s 0.0003%) and only 2 cases reported from the 346 million people given a Moderna vaccine (that’s 0.00000057%) (18).


If you're worried about long-term side effects, don’t be. Making antibodies to the spike protein shouldn’t have any long-term consequences (19). But like many things, we can’t know with 100% certainty. Many of the people not getting vaccinated think that they are healthy enough so that if they got the disease, they’d be OK. But it’s not just about that one person—a nonvaccinated person provides a place for the virus to spread, and that person could infect someone little like me (20,21) or old like Grandpa who may not be able to fight off the virus. Right now 1 in 4 new infections are happening in kids (22), which is really scary because we’re not old enough to get the protection offered from the vaccine.


Both sides seem to be scared but we need to untangle what might be a future problem vs. what is a real danger now. There are some rare side effects, and we have ways to screen against those now, and while there may be some long-term risk we don’t know about, it’s also likely there might not be any problem at all. What is real is that people who get COVID have long-term problems or worse-- they die. Right now, 85% of people in the hospital and 99% of people dying from COVID are not vaccinated (23).


Did you know that penicillin was originally made from mold? Sir Alexander Fleming discovered what has become the life-saving antibiotic and it’s the same stuff found on moldy bread (24). Think of how scary it must have been for the first patients to take a mold-derived medicine. But back then the risk of dying from infection was real—not unlike today’s risk of dying from COVID. Now we all know penicillin is safe and saves lives. I think in the future we will look back and say the same thing about the vaccine. I just hope we don’t lose our window to stop this!


Love you to the moon & back!

-Mc

Your 3-month-old niece


P.S. I know there’s a lot of info out there these days, make sure to look for peer-reviewed sources - that means the data and conclusions have been vetted by a larger scientific community.


References

1. Atzrodt, C. L. et al. A Guide to COVID‐19: a global pandemic caused by the novel coronavirus SARS‐CoV‐2. Febs J. 287, 3633–3650 (2020).

2. V’kovski, P., Kratzel, A., Steiner, S., Stalder, H. & Thiel, V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat. Rev. Microbiol. 2020 19319, 155–170 (2020).

3. J, B. et al. COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge. J. Clin. Med. 9, 1753 (2020).

4. Machhi, J. et al. The Natural History, Pathobiology, and Clinical Manifestations of SARS-CoV-2 Infections. J. Neuroimmune Pharmacol. 15, 1 (2020).

5. Ragab, D., Eldin, H. S., Taeimah, M., Khattab, R. & Salem, R. The COVID-19 Cytokine Storm; What We Know So Far. Front. Immunol. 11, 1446 (2020).

6. Boban, M. Novel coronavirus disease (COVID‐19) update on epidemiology, pathogenicity, clinical course and treatments. Int. J. Clin. Pract. 75, (2021).

7. DA, B., RM, G. & FJ, M. Severe Covid-19. N. Engl. J. Med. 383, 2451–2460 (2020).

8. Majumder, J. & Minko, T. Recent Developments on Therapeutic and Diagnostic Approaches for COVID-19. AAPS J. 23, (2021).

9. Bettini, E. & Locci, M. SARS-CoV-2 mRNA Vaccines: Immunological Mechanism and Beyond. Vaccines 9, 1–20 (2021).

10. J, Y. et al. A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity. Nature 586, 572–577 (2020).

11. ML, M. & CA, G. Genome-editing Technologies for Gene and Cell Therapy. Mol. Ther. 24, 430–446 (2016).

12. Nicholson, L. B. The immune system. Essays Biochem. 60, 275 (2016).

13. Antonelli, M. et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect. Dis. 0, (2021).

14. FP, P. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 383, 2603–2615 (2020).

15. LR, B. et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 384, 403–416 (2021).

16. R, S. & P, D.-C. Mechanisms of viral mutation. Cell. Mol. Life Sci. 73, 4433–4448 (2016).

17. M, C. et al. Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials. Infect. Dis. poverty 10, (2021).

18. Selected Adverse Events Reported after COVID-19 Vaccination | CDC. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html.

19. Anand, P. & Stahel, V. P. The safety of Covid-19 mRNA vaccines: a review. Patient Saf. Surg. 2021 151 15, 1–9 (2021).

20. MJ, D. et al. Hospitalizations Associated with COVID-19 Among Children and Adolescents - COVID-NET, 14 States, March 1, 2020-August 14, 2021. MMWR. Morb. Mortal. Wkly. Rep. 70, 1255–1260 (2021).

21. DA, S. et al. Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0-17 Years - United States, August 2020-August 2021. MMWR. Morb. Mortal. Wkly. Rep. 70, 1249–1254 (2021).

22. Children and COVID-19: State-Level Data Report. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/children-and-covid-19-state-level-data-report/.

23. Rosenberg, E. S. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status — New York, May 3–July 25, 2021. MMWR. Morb. Mortal. Wkly. Rep. 70, 1150–1155 (2021).

24. Ligon, B. L. Penicillin: its discovery and early development. Semin. Pediatr. Infect. Dis. 15, 52–57 (2004).




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