Hurts So Good
Reactogenicity--embrace it
By now, the world has seen vaccines against COVID-19 start flowing from factories into the deltoid muscles of healthcare workers around the world. Vaccine from Pfizer, and soon Moderna and, likely, AstraZeneca, have made their way from the laboratory, through clinical trials, and into distribution.
These vaccines have shown effectiveness beyond the hopes and expectations of many of us in Infectious Disease and Epidemiology. Our fear was a vaccine with effectiveness similar to influenza—maybe 60% to 70% effective, if at all. Instead, the studies to date show effectiveness of 94% or higher, even in older people who often have decreased immune response. Along with this tremendous immune response has come an expected effect—reactogenicity. Reactogenicity refers to the unwanted effects of vaccination that occur soon after administration. Full FDA report on safety and effectiveness here.
Reactogenicity is part of the immune response sometimes seen as a result of immunization. While almost all vaccines may provoke a reaction, some are more notorious than others. Symptoms may include pain at injection site, fever, body aches or malaise. A recent vaccine to protect against shingles, Shingrix, has been notorious for provoking reactogenicity.
Factors associated with reactogenicity.
While it may be tempting to say that there is a “No pain, no gain” aspect to reactogenicity and immunization, there is not any data to support this assertion. Instead, as vaccines are evaluated, it is found that some have more tendency to elicit reactions than others.
For the Pfizer/BioNTech COVID-19 vaccine, reports from the Phase 3 studies indicate there are significant reactions in the first few days after administration, when compared to placebo. As the table below shows, about three-quarters of people receiving vaccine reported a reaction at injection site within a week, compared to only about 10% of people who received placebo. (Interesting to note the NOcebo effect of 10%. A nocebo effect is when the inactive agent causes negative effects. A placebo effect is when an inactive agent causes positive effects.)
From fda.gov
Every vaccine may have a different set of effects after administration. For the Pfizer/BioNTech vaccine against COVID-19, very common effects that occurred at a greater rate than placebo after administration include fever, fatigue, headache and chills. Joint pain was only slightly higher than placebo. These effects tended to occur most commonly the day after administration, and fade away within 3 days.
Recent reports from the United Kingdom and Alaska have included a few people with severe allergic reactions. In the Phase 2 and 3 studies, which included over 40,000 people, 2 people died in vaccine group and 4 people died in the placebo group. Neither of the people in the vaccine group were felt to have died as a complication of the vaccine. It is important to remember, people are dying from COVID-19.
A challenge for the vaccination effort is managing expectations around reactogenicity. These reactions are expected and should not be considered as either allergic reactions or even a reason to not be immunized. As Maryn McKenna notes in wired.com, debunking (or prebunking) mis- and disinformation around these expected effects may impact our ability to immunize the broad swaths of the general population that will need to be done to limit transmission, not just protect the front line healthcare workers, first responders and essential workers that will get the initial allotments of vaccine.
As I make rounds in the hospitals where I serve, the most common questions I get are, “Will you get the vaccine?”, “When will you get the vaccine?” and “Which vaccine will you get?” The answers to these questions are simple, “I will take whichever vaccine is offered to me soonest.” The COVID-19 pandemic is a true public health emergency. My reason to get immunized ASAP is to protect myself so that I can continue to serve my patients, and hopefully reduce the likelihood that, should I be exposed, I will not transmit the infection to my patients, coworkers or family. I will continue to wear a mask, as the initial studies of vaccine focused on illness and not transmission. The mask will come off when our public health authorities say it is appropriate to do so. Likely this will not happen until the majority of the population has been immunized and COVID-19 transmission has been truly crushed.
Other questions I have received:
I have heard that taking an anti-inflammatory or antifever medicine will make the vaccine less effective. Is this true?
This is a theoretical concern that has been seen in laboratory settings that taking these medications prior to immunization may decrease the effectiveness of vaccines. These medications are not recommended to take as a preventive (or prophylactic) treatment for side effects, but may be used after the vaccine is given—if needed.
I have heard that the vaccine may cause infertility. Is this true?
This rumor was started by a former Pfizer employee who is a medical doctor in the United Kingdom. The very theoretical basis for this rumor is the concern that the spike protein of the virus to which vaccine is directed may look like a protein on the placenta. The rumor is that the vaccine would cause an immune reaction against the placenta. Experts in maternal immunology do not feel that placental proteins look like SARS-CoV-2 (the virus that causes COVID-19 disease) proteins. I have seen very sick pregnant women with COVID-19. So far, there is no information—good or bad—about using the vaccine in pregnant women. CDC is tracking COVID-19 and pregnancy outcomes. There is no consensus as to whether COVID-19 contributes significantly to adverse pregnancy outcomes, but according to CDC pregnant women with COVID-19 tend to be sicker than non-pregnant women.
The Pfizer/BioNTech and Moderna vaccines have mRNA. Won’t that change my genetic makeup? Or cause cancer?
These two vaccines use a type of genetic material, messenger ribonucleic acid or mRNA, to instruct the vaccine recipient’s cells to make the spike protein of COVID-19. mRNA does not penetrate into the nucleus of the cell where DNA is stored. DNA is the code we are all born with that instructs our cells to make RNA that is then used to make proteins. DNA makes RNA. RNA makes protein. There are some viruses that do insert their genetic material into human DNA. These are called retroviruses. The most well-known of these is HIV—the human immunodeficiency virus—which causes AIDS.
There is no evidence that mRNA can be inserted back into the genes in the cell to cause cancer or change genetic makeup.
