With the recent news that the CDC and FDA recommend pausing the Johnson and Johnson vaccine, many are questioning the safety of this and other COVID-19 vaccines. What does this pause really mean? And what do we know about the safety of available COVID vaccines? Before we dig into the recent news story, let’s take a look at overall COVID-19 vaccine safety and safety monitoring systems.
What Do We Know About COVID-19 Vaccine Safety?
The Advisory Committee on Immunization Practices (ACIP) includes 45 medical and public health professionals from across the country as well as a representative of the general public. These include experts in vaccinology, immunology, virology, public health, pediatrics, internal medicine, infectious diseases, nursing to preventive medicine. All of these representatives bring their expertise to the discussion and have dedicated their career to ensuring the safety and efficacy of vaccines. Before approval for each vaccine or recommendation for change, the committee hosts an open to the public meeting which rigorously reviews safety and efficacy data to decide if it should be used in the United States.1 The data they were initially looking at for COVID-19 vaccines were from the phase III clinical trials. These trials each include tens of thousands of participants who either receive a vaccine or an equal dose of saline placebo shot, which is just water that matches the saltiness of our body. They then monitor participants for any developing conditions.2,3
During the trials, no concerning reactions were seen in any of the approved vaccines. Among side effects seen during the trials were the following injection-site reactions:
Among the systemic reactions were the following:
I should note that reaction to the vaccine can include multiple or none of the above reactions, and injection-site reactions are much more common. Also, the stronger response is typically seen after the second dose. All of the above reactions are normal and are a result of immune responses to components of the vaccine or the spike protein made by our cells. These effects typically resolve within 1-3 days. In the Moderna trial, some reports of Bells palsy occurred in the vaccinated group, but not significantly more than the placebo group.4
However, these were stage III trials, which are limited by the number of participants and the duration of the study. What we really want to see is if these results can translate to the real world and if there are any very rare side-effects or unseen side-effects only afflicting certain populations. The late pioneering vaccinologist Maurice Hilleman has been credited with once saying that “I never breathe a sigh of relief until the first 3 million doses are out there”.5 Over 145 million doses of COVID-19 vaccines were administered in the United States alone from December 14, 2020, through March 29, 2021.6 What have we learned about safety after all of these vaccinations? To answer this, we must consider phase IV trials and analyze vaccine adverse event reports.
What Have We Learned From VAERS?
COVID-19 vaccine safety monitoring has been the most intensive and comprehensive in the history of the US with both self-reported events through VAERS and active surveillance through v-safe.7 VAERS (Vaccine Adverse Events Reporting System) has been around since 1990, while v-safe was developed for the COVID-19 vaccines. At this point in time, safety monitoring reports have been consistent with the initial data from phase III trials. Most effects are minor and at the site of the injection, and no concerning patterns have been seen.8
To determine if a concerning effect of the vaccine is observed, we must compare the incidence of a condition in vaccinated people with what would be expected in the general population. If there is no greater chance of something happening after receiving a vaccine than if you had not, then this would not be immediately concerning. If significant differences are observed, this is taken very seriously and delved into.
Polyethylene glycol (PEG) seen in many injectable drugs, causes anaphylaxis in rare cases. Because mRNA vaccines use lipid nanoparticles containing PEG and nearly 200 million doses have been administered, we have seen anaphylaxis occur. Anaphylaxis is seen at a rate of 2.5 cases per 1 million vaccinations, making this a rare adverse reaction. Because there are effective treatments for anaphylaxis, which occurs almost exclusively within the first 30 minutes following vaccination, the risk of anaphylaxis is greatly outweighed by the benefit of the vaccines.9 Precautions are still taken by screening people for histories of allergic reactions to injectable medications or ingredients of the vaccines and monitoring vaccinated people for 15-30 minutes after getting the shot.10
Critically, VAERS data are simply self-reported incidents of adverse events that happen after vaccination. An event reported to VAERS could very well be happenstance or exaggeration. The purpose of VAERS is not to record every reaction to a vaccine, but to detect alarming trends before they become a problem. Just because there may be more reports of a certain adverse event does not mean it is more alarming. We must ask, how does the incidence of this event compare to the general population? Is this event plausibly connected to the vaccine?11
Why Recommend Pausing Vaccinations From J&J?
The recommendation serves two main purposes:12
- Allow time for proper assessment of the risk
- Be sure that healthcare providers know how to care for these adverse events
What are the adverse events? Reports of six J&J vaccinated women ages 18-48 who developed cerebral venous sinus thrombosis, or blood clots in the veins returning blood from the brain back to the heart, in combination with a low platelet count. One of these six died from their blood clot.
Why would there be more clots if someone has fewer platelets? This may be because all of those missing platelets are gone as they have already formed clots. What is causing these clots? A possible cause is the antibodies directed against the adenovirus vector or spike protein inadvertently binding platelet-factor 4 (PF4), causing an intense platelet activation cascade. This would be similar to what researchers are investigating about the previously reported adverse events associated with AstraZeneca vaccines.13 These similarities are significant because the two vaccines rely on adenoviral vector vaccine technology.
Similar to the AstraZeneca vaccine, these adverse events are extremely rare. For the J&J vaccine, it is about a 1 in 1,133,333 chance of a clotting event from what we know.14 For comparison, if you are hospitalized with COVID-19, your chances of developing a blood clot may be as high as 1 in 6.15 This is not to mention that about 1 in 8,000 Americans died from COVID-19 since early last year, making it the third leading cause of death in 2020.16
Does this mean we should abandon the use of the J&J vaccine? No, this is a pause meant to evaluate whether we should change recommendations for some Americans and inform clinicians what to look for and how to treat it. For example, heparin is the standard anticoagulant drug used to treat blood clots in this setting. However, with immune thrombotic thrombocytopenia as seen with the AstraZeneca vaccines, this may be harmful. The pause gives time to investigate these cases, allow for the possibility of more cases to be surfaced, and inform clinicians how to treat these events effectively.17 A possible outcome may be that women ages 18-48 may be recommended to receive a different vaccine to minimize risk, as all blood clot incidents were in this demographic.
So, Are They Safe?
Vaccines must be some of the safest medical treatments you can get because they are meant to be given to healthy people on a large scale whose individual risk may be small. What we have learned from COVID vaccine trials and safety monitoring suggests that they are all very safe. Additionally, the individual risk to benefit ratio is small for most people, meaning that the amount of risk involved in being vaccinated is greatly outweighed by the risks involved with getting COVID-19, despite how small your individual risk of death by COVID may be. The fact is our population-scale risk to benefit ratio is much smaller for getting vaccinated, as we have seen COVID-19 become the third leading cause of death.18 Additionally, these death reports have been closely monitored for accuracy further supporting the direct impact of COVID-19 on mortality in our country.19