Prior to this year, the fastest any vaccine had been developed from viral sampling to approval was four years, in the 1960s for mumps. As outlined in Nature, the development of the COVID-19 vaccines broke through paradigms of what was considered possible in vaccine development. The breakthroughs didn’t come out of nowhere. Decades of research prepared scientists to respond with lightning quickness and safety, leading to one of the most exciting scientific developments of recent history.
For many people, 2020 may have felt a bit like all those decades of basic science research. Lots of work, little to show for it, like a Basset Hound trying to sprint after a squirrel. But 2021 is set up to be different. As we go over in this article, the revolutionary vaccines use all of that past work to create a world with hope and optimism for the future.
On December 10, 2020, the New England Journal of Medicine released a publication summarizing the Phase 2 and 3 COVID-19 vaccine clinical trial results for the Pfizer/BioNTech vaccine that is being distributed to high-risk people and medical professionals now. The Phase 1 clinical trial results were published in October in the New England Journal of Medicine. In addition, on December 8, 2020, the Lancet published Phase 2 and 3 clinical trial results for the Moderna vaccine, following up on Phase 1 publication. Both vaccines use the same general approach, require two doses, and have similar reported side effects. The big conclusion: both COVID-19 vaccines are safe and effective, without substantial side effects for most people.
Many athletes have asked us to review vaccine considerations for endurance athletes. This article provides a basic overview of the vaccine and how it works, along with some possible considerations for athletes. We focus on the Pfizer/BioNTech vaccine as it was the first to achieve FDA approval. Although there are small nuances between the two vaccines, the considerations for athletes are similar. Our episode of the Some Work, All Play Podcast from last week provides a deeper summary. Play it at 2x speed to hear chipmunks get excited about science.
Both vaccines use messenger ribonucleic acid (mRNA), which carry instructions for creating proteins. With this approach, the injected mRNA instructions enable our bodies to create the “spike protein”—one of the proteins found on the surface of the COVID-19 virus involved in enabling the virus to enter our cells. You probably know the targeted protein from illustrations of the virus featuring those spiky red appendages. It feels like poetic justice to target the virus via one of its most distinctive features.
Following injection, our immune systems will recognize the mRNA-created spike protein as a foreign intruder and will start making antibodies and producing an immune cascade to specifically target it. If our bodies are exposed to the COVID-19 virus after vaccination, we can produce a full “Home Alone” immune response against the spike protein to prevent viral entry into our cells. Antibodies prevent COVID-19 cell invasion in much the same way that the Home Alone kid successfully defended his house from burglars with cans of paint and blow torches.
The COVID-19 vaccine is the first approved mRNA vaccine in the United States. However, scientists have been working on mRNA technologies for decades in vaccine and cancer research. The key challenge for researchers was that injected mRNA is highly susceptible to the body’s natural defenses en route to the target cells. Injecting mRNA into the body alone is like dropping an ultrarunner in the middle of a safari with no map or water. In the COVID-19 vaccine, mRNA strands are wrapped in lipid nanoparticles to protect the mRNA from breakdown by enzymes and to help the mRNA reach their target cells, a crew and aid station to accomplish the goal.
The mRNA approach differs from standard vaccine approaches that introduce a weakened germ into the body (live attenuated vaccines) or a killed germ or fragment of germ into the body (inactivated vaccines). In sum, the COVID-19 vaccine elicits the immune response without introducing the actual COVID-19 virus into our bodies. It may be normal to be a bit wary about vaccines given some of the misinformation-filled social-media posts out there, so cut yourself and others slack if you see those feelings. It may be human nature to respond to uncertainty with fear. But there is nothing to fear here. The COVID-19 vaccines are using a process our bodies are doing constantly, with zero virality, and strikingly low risk. Science is remarkable.
The clinical trials for the Pfizer/BioNTech and Moderna vaccines examined safety, dosage, and response rates, finding that multiple doses separated by a few weeks were most effective in preventing COVID-19 infection.
Let’s look at the Pfizer/BioNTech study more closely. The clinical trial involved 43,448 participants receiving an injection, half with the vaccine and half with a placebo, with two doses 21 days apart. Vaccine efficacy was 52% between the first dose and second dose and 91% within a week of the 2nd dose. But the true test for the researchers was effectiveness at seven or more days after the second dose in participants with no evidence of existing or prior COVID-19 infection.
In the vaccine group, eight participants contracted COVID-19 after that time. In the placebo, group, 162 participants contracted COVID-19. That’s where the 95% effectiveness number you have probably heard about comes in, with a 95% confidence interval of 90.3 to 97.6 percent. After the first dose, there were 10 cases of severe COVID-19, with just one among the vaccine group. The effectiveness applied across different subgroups by age, sex, race, ethnicity, baseline body-mass index and the presence of coexisting conditions.
From the outside, it seems like a scientific miracle. Researchers in China put the genome of the virus causing COVID-19 online shortly after it appeared, researchers elsewhere in the world were working on mRNA vaccines rapidly after, and clinical trials began in what seems like an instant. But as outlined in Nature, it’s not a miracle. It’s the product of decades of basic science and applied research about mRNA and vaccines, combined with an overwhelming international effort to make it happen. The key question for athletes: what happens after the vaccine?
The vocabulary word of the day is reactogenicity, which refers to normal physical responses to a vaccination injection. You’re probably familiar with reactogenicity from the flu shot, when many people describe fatigue for a day or two. Here is the next exciting finding in the study: reactogenicity of the COVID-19 vaccine is not high, and serious adverse events were similar in the vaccine group and the placebo group.
The study looked at adverse event data for 14 weeks after the 2nd vaccine dose, or 17 weeks from the first dose. Mild-to-moderate pain at the injection site was the most commonly reported local reaction, with less than 1% reporting severe pain. Interestingly, pain was reported more often in younger participants than older ones. The discomfort mostly resolved in one or two days.
Systemic reactogenicity was also reported more often by younger participants, likely related to immune system responses, with increased reactions after the second dose. Just over 50% of younger participants reported fatigue and headache after the second dose of the vaccine, compared to 23% of those that received a placebo. Fever was reported by 16% of younger participants after the second dose (11% of older participants), with smaller percentages reporting fever after the first dose. Fever and chills were observed in the first two days after injection, then resolved shortly thereafter. Severe fatigue was reported in 4% of those that received the vaccine, which resolved on short time scales.
Adverse events were uncommon. Sixty-four (or 0.3%) of the vaccine recipients reported lymphadenopathy, or swollen or enlarged lymph nodes, compared to six in the placebo group. It mostly resolved within 10 days. Just four serious adverse events were reported among vaccine recipients, including a shoulder injury from the shot, lymph-node enlargement, paroxysmal ventricular arrhythmia (irregular heartbeat) and right-leg paresthesia (tingling). Four participants in the placebo group died and two in the vaccine group, all of causes considered unrelated to the placebo or vaccine.
If the true incidence of adverse events is 0.01%, then the two-month median follow-up time has an 83% chance of detecting at least one adverse event. Thus, there’s a small chance that there will be other adverse events, but those chances drop over time as researchers continue follow-up studies for the next two years. In addition, the duration of vaccine protection has yet to be determined.
A problem in the long-term safety studies is that the vaccine is so effective that it cannot ethically be withheld from the placebo group. The study will still continue to evaluate safety and efficacy for two years after the second dose, just without the context of the placebo group. The catch-22 of strong science is losing your control group.
The study did not evaluate whether the vaccine prevents asymptomatic infection and COVID-19 transmission. Future studies are needed to evaluate ability to transmit COVID-19 after infection and vaccinated individuals should still wear masks, practice social distancing and follow standard COVID-19 protocols until guidance changes.
Adolescents (under age 16), children, pregnant women and immunocompromised persons were not included in the study and further research will be done to evaluate safety and efficacy in these populations. It will take time for vaccinations to roll out to the general public. Protecting our healthcare workers, essential workers and high-risk populations is the key focus right now.
Finally, there are no studies on athletic performance or related physiological variables. However, there are no reported mechanisms that would cause performance reduction, outside of the one to two day fatigue, or the potentially longer window for more severe adverse events, which would resolve, and which were exceedingly rare.
Putting it all together
Responses to the vaccine seem to be normal and short-lived. Meanwhile, contracting COVID-19 can have long-term effects on the cardiovascular system (some earlier findings are summarized in a Trail Runner article here). In athletes we coach that have contracted COVID-19, response rates vary, but all have had a dent in their training, with some having longer-term effects over months. No similar issues are reported for the vaccine.
In the last week, a number of athletes we coach have received the first dose of the vaccine. Anecdotally, we have seen no adverse responses yet beyond soreness at the injection site. And a couple of athletes had especially strong runs, including a professional runner training for a race and doing a back-to-back long run weekend. These athletes all work in medical fields and have seen the terrible havoc caused by the virus. Along with the first vaccine injection seemed to come a side effect of joy, with hope for the future.
After receiving the vaccine, consider resting or just running very easily for one to three days, listening to your doctor, all medical advice and your body. The easy period may be especially important after the second dose, when the short-term fatigue and fever rates are higher. We are currently planning for short one- to two-day rest periods after the second dose for athletes we coach, but will adjust based on additional information.
If symptoms persist, see a medical professional and don’t run through any abnormal issues. But based on the information we have, you should be back to full training quickly, without any long-term impacts on athletic performance.
We are heading into winter, but after reading all about these vaccines, it feels a lot more like spring. As we move into 2021, the sun is rising on a bright future that will eventually include more races and group runs. And maybe most fun of all, something else will return too: Big, jolly, loving bear hugs. We got this.
This article originally appeared at trailrunnermag.com.
Megan Roche received her medical degree from Stanford University and is currently pursuing a PhD in Epidemiology from Stanford. David and Megan partner with runners of all abilities through their coaching service, Some Work, All Play. They host the Some Work, All Play podcast on running (and other things), and they wrote a book called The Happy Runner.