Vaccines pose particular ethical questions that other pharmaceuticals do not. Vaccines are given to an otherwise healthy person in hopes of preventing infection and curbing community spread of a disease. There is both a personal component and a public health component in considering the risks and benefits of taking a vaccine. Furthermore, a vaccine for COVID-19 will have its own set of ethical issues. Multiple vaccine candidates are being developed at an accelerated pace with the goal of slowing down the worldwide pandemic of COVID-19, the disease caused by SARS-CoV-2, a novel coronavirus. Because of the rapid onset of the pandemic, COVID-19 is considered a global disaster. This means bioethicists must make decisions that weigh the immediacy of the effects of the disaster with ethical best practices.
Major ethical issues concerning COVID-19 vaccines include:
- Whether fast-tracked vaccines that short-cut Phase 3 trials, as in the case of two vaccines out of Russia and three out of China, are safe.
- Whether Emergency Use Authorization by the U.S. FDA of any of the vaccine candidates is valid.
- Whether challenge trials are ethical, as in the case of the Imperial College of London trial in the UK.
- Whether there is a fair way to distribute limited doses of the vaccine, and who should receive a vaccine first.
- Whether the first vaccine approved by the FDA is the best vaccine and whether vulnerable populations should get the first vaccine or the “best” vaccine.
- Whether people are morally obligated to get a COVID-19 vaccine, especially those who have already had the virus or are low-risk populations.
- Whether there is a reason for conscientious objections to certain vaccines based on their development using fetal cell lines.
- Whether a vaccine is necessary.
- Whether mRNA vaccines, such as Moderna and Pfizer’s vaccines, are ethical and safe.
- Whether adenovirus vaccines, such as Johnson & Johnson and AstraZeneca, are ethical and safe.
- Whether the U.S. government can mandate a COVID-19 vaccine.
- Whether vaccine passports or vaccination certificates are ethical.
- Whether we should be concerned about different variants of SARS-CoV-2.
Are fast-tracked vaccines that short-cut Phase 3 trials, as in the case of two vaccines out of Russia and three out of China, safe?
On July 25, the Chinese Military authorized limited distribution of a COVID-19 vaccine developed by CanSinoBio following Phase 2 trials. On August 11, Russia announced that its health regulator approved a COVID-19 vaccine developed by Gamaleya Research Institute for limited use (Russia later backtracked on how widely it would distribute the vaccine). Both countries likely made these announcements for political reasons, as evidenced by Russia re-naming the vaccine program Sputnik V and China’s efforts to rectify its global reputation, such as a media campaign to re-write the narrative of the origins of the coronavirus as well as efforts in “vaccine diplomacy”. More recently, Russia, in particular, has engaged in disinformation campaigns that misrepresent the safety of the Pfizer and Moderna vaccines. This campaign also claims Pfizer rushed Phase 3 approval, which could undermine people’s genuine questions about vaccine safety and their desire to make informed decisions. Additionally, the U.S. Department of Justice has indicated that both Russia and China have hacked into U.S. research institutions to obtain intellectual property related to COVID-19 therapies.
Most bioethicists agree that Russia’s and China’s decisions to distribute vaccines before completing Phase 3 trials are ethically problematic and potentially dangerous. The vaccines could turn out to be marginally effective or not effective at all, which happens often in Phase 3 trials of vaccines. Or a vaccine could turn out to have an unforeseen side effect that was not discovered in Phase 1 or 2 trials.
Typically the drug review process begins with pre-clinical studies in the laboratory and in animal models. Once approved for clinical research in human volunteers, the drug then moves to Phase 1 studies. Phase 1 studies involve a small number of volunteers to test for side effects, minimum effective dosage, and method of administration (e.g., intravenously, orally, etc.). In Phase 1, researchers are not testing for efficacy—whether the drug works. Then the drug moves to Phase 2 trials, which involve a larger set of volunteers. This phase looks for side effects that did not show up in Phase 1, and researchers look for preliminary evidence for efficacy. Many times Phases 1 and 2 can be combined, as was the case with most of the COVID-19 vaccine candidates. Finally, Phase 3 involves a large number of participants, usually around 10,000 for vaccines, and tests for efficacy as well as any long-term side effects. This process generally takes many years, and only 25–30% of drugs pass Phase 3 trials.
While it varies from country to country, the coronavirus death rate is under 1% for the general population, but much higher for the elderly and vulnerable. While it is troubling that over two million people worldwide have died from COVID-19, the death rate does not merit bypassing Phase 3 trials to determine vaccine safety and efficacy in a large group. Even in the face of how quickly the SARS-CoV-2 virus can spread through a population, adverse events from the vaccine or even an ineffective vaccine would be worse. If only healthy people are given a vaccine that turns out to be ineffective and they engage in behavior that induces spread, then the ones most likely to be harmed by the faulty vaccine are the vulnerable.
Furthermore, death rates have fallen since the beginning of the pandemic, largely because medical professionals and researchers have learned how to treat the disease and how to mitigate the severe cases. This buys additional time for vaccine researchers and governmental institutions to take precautions to ensure that the vaccine works and is safe. Overall, the risks to distributing a vaccine for COVID-19 before determining efficacy and safety in a large cohort (i.e., Phase 3 trials) outweigh the benefits.
According to the New York Times vaccine tracker, Gamaleya Research Institute in Russia published the results of the Phase 3 trials of their vaccine, called Sputnik V or Gam-Covid-Vac, on February 3, 2021 in the Lancet. The Lancet article reports an efficacy of 91.6% with mostly mild side effects after two doses taken 21 days apart. Their Phase 3 trial was randomized, placebo-controlled, double-blind, and spanned several centers. The study included 16,427 participants who received the vaccine and 5,435 who received the placebo. Overall, of the 78 cases of COVID-19, 62 were in the placebo group and 16 were in the vaccine group.
Gamaleya and AstraZeneca/Oxford in the UK are partnering in a study to see if a combination of the two adenovirus vaccines will confer better efficacy than the AstraZeneca vaccine alone. Gamaleya is also exploring a one-dose version of their vaccine called “Sputnik Lite.”
CanSino Biologics vaccine, Convidecia, was approved conditionally by the Chinese military on June 25, 2020 as a specially needed drug. In August 2020, CanSino Biologics started Phase 3 trials in several countries, and an independent committee gave approval for CanSino to continue their Phase 3 trial. It has been shown to have an efficacy rate of 65.28%, although CanSino has not published its Phase 3 trial data. Other Chinese vaccines that include inactivated virus vaccines are Sinopharm, Sinovac, and Sinopharm-Wuhan. All were approved in China and have emergency approval or limited use in a few other countries prior to conducting or publishing Phase 3 results.
Is Emergency Use Authorization by the U.S. FDA of any of the vaccine candidates valid?
While circumventing Phase 3 trials is ethically problematic, there are some things drug companies, researchers, and regulators can do to speed up Phase 3 trials. In Phase 3 trials, the investigator gives a group of volunteers either the vaccine or a placebo. Neither the investigator nor the clinical trial participant knows whether the participant received the vaccine or placebo. This ensures that the investigator or those involved in the trial do not give the participant subtle clues that he or she received the vaccine or placebo. This is called a double-blind clinical trial. Double-blind, placebo-controlled trials are the best way to determine if a drug really does perform better than a placebo.
During the trial, the drug company will do an interim analysis after a certain number of volunteers in the trial contract the disease. For example, Moderna did an interim analysis at 53 and 106 positive COVID-19 cases. To truncate the time from injection to the interim infection numbers, Moderna enrolled 30,000 people in its Phase 3 study. Typical vaccine studies enroll less than 10,000 people and take several years before infection goals are met. Paradoxically, surges in COVID-19 cases could actually speed up Phase 3 trials, while lags in the number of cases would delay the trial until enough people become infected.
There are both advantages and disadvantages to this and similar protocols. On the one hand, by having a large number of people enrolled in a Phase 3 trial, rare side effects are more likely to show up and can be recorded. On the other hand, by speeding up the process, the vaccine companies will not have data on long-term safety before Emergency Use Authorization is given. Additionally, because the pool of volunteers is much larger, this exposes more people to an unproven vaccine.
Relatedly, some have questioned how long drug companies should study these vaccines before determining that they likely will not have side effects. The FDA has said that it will require at least two months of observation after half of the trial participants have received their final dose of the vaccine before granting Emergency Use Authorization. Peter Marks, director of FDA’s vaccine division, told The Atlantic that they chose two months because most adverse events show up by then.
Others question whether vaccines should even be authorized under the Emergency Use Authorization designation. In a commentary article for STAT News, members of the Vaccine Working Group, an independent non-profit organization that addresses policies regarding the testing and distribution of vaccines for COVID-19, encouraged the FDA to grant early use of COVID-19 vaccines through expanded access (also called “compassionate use”) rather than Emergency Use Authorization. The authors point out that the pandemic is a crisis, not an emergency, and fast-tracking the widespread distribution of vaccines was never the intention of the Emergency Use Authorization designation. Emergency Use Authorization was originally intended for bioterrorism. Expanded access has been used for meningococcal disease and yellow fever vaccines, and it would allow the most vulnerable to receive the vaccine before widespread distribution of the vaccine but would still have rigorous monitoring for safety and efficacy among the study groups. Expanded use has greater ethical oversight and requires additional informed consent requirements compared to Emergency Use Authorization.
Furthermore, several members of the FDA’s Vaccines and Related Biological Products Advisory Committee are concerned that granting Emergency Use Authorization would stymie long-term assessments of safety and efficacy, which could result in the vaccine maker not acquiring enough data for a full license to sell and distribute the vaccine. The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) voiced similar concerns over the lack of long-term data. The FDA questioned whether the vaccine company should “un-blind” the study, allowing the volunteers who received a placebo the option of getting the vaccine, which would be permissible under Emergency Use Authorization. In doing this, researchers will no longer have a control group to compare the vaccine to. This may leave certain questions unanswered, such as whether the vaccine reduces the number of severe COVID-19 cases, or whether the vaccine prevents the spread of COVID-19. Currently, the leading vaccine candidates—Pfizer, Moderna, Johnson & Johnson, and AstraZeneca’s vaccines—have shown that they prevent symptomatic COVID-19 disease. It would take many more months to determine if any of these vaccines prevent spreading the disease, an important question for ascertaining which vaccine is the best vaccine for certain populations.
Update (March 2021): Preliminary reports show that Pfizer, Moderna, and AstraZeneca may stop transmission of the disease, but more rigorous tests are needed to know for sure.
Overall, there are good reasons to approve giving vulnerable populations and high-risk individuals vaccines that have met their primary endpoints and shown no evidence of adverse effects after two months. However, there are also good reasons to continue studying these vaccines to ensure there is adequate data to optimize protocols on dosage and distribution in the future. In that vein, several experts argue that expanded use should be granted to COVID-19 vaccines rather than Emergency Use Authorization. Others suggest granting Emergency Use Authorization, but not “un-blinding” study participants.
A challenge trial is when healthy participants are given a vaccine candidate and then intentionally infected with the pathogen it is meant to protect against under controlled conditions. The Imperial College of London is leading a challenge trial to test a vaccine for COVID-19. The college is working with the UK government’s Vaccines Taskforce, the Royal Free London NHS Foundation Trust and hVIVO, a company that has conducted several human challenge trials.
A challenge trial for a COVID-19 vaccine presents an ethically contentious study protocol because it is intentionally infecting an individual, in this case people ages 18 to 30, with a novel virus whose effects, particularly its long-term effects, are still not fully known.
Some question whether human challenge trials are truly helpful. For one, this type of trial limits the demographics that can be studied. Children and the elderly, for example, are ineligible for a challenge trial, even though the elderly would be one of the populations that would most benefit from a vaccine. Also, unlike double-blind placebo-controlled trials, human challenge trials do not test whether the vaccine works when participants are engaging in normal behavior and in typical settings. The virus is administered in safe doses via a spray in the nose or mouth and according to the Imperial College London protocol, the participant will remain in a “high-level isolation unit” for observation and to prevent community spread.
According to Lambkin-Williams and DeVincenzo, who have done challenge trials for a vaccine for RSV (Respiratory Syncytial Virus), these trials can be helpful in moving a drug out of Phases 1 and 2. However, they caution that because COVID-19 does not have an effective treatment, the virus used to infect trial participants should probably be a synthetic virus. This would further remove the challenge trial from a realistic scenario.
Update (March 2021): The new protocols will be using a variant of the virus that was first circulating in the UK in March 2020. This variant is known to not have severe side effects and is less deadly, particularly in the population being studied. Later in the trial, some volunteers may be given an approved vaccine and then will be exposed to one of the new variants to see how well the vaccine works for different variants of the virus.
Rather than testing for vaccine efficacy as was the original protocol, the challenge trials will look at the smallest amount of SARS-CoV-2 that results in infection. They will also study how the body’s immune system reacts to infection. The hope is this will lead to better, more targeted vaccines and therapies.
An article in The Lancet says that the lead researcher for the trial has conducted challenge trials for respiratory viruses for over 10 years and will do as much as he can to mitigate the participants’ risks. Even given these assurances, many people are concerned about participant safety and the public health ramifications if a participant should die from COVID-19.
Overall, there is some question as to the value of challenge trials in such a constrained population and under a clinical setting (i.e., not what we experience in everyday life). Challenge trials are also ethically problematic because they involve intentionally infecting otherwise healthy people with a pathogen. While we have learned much about COVD-19 in the past year, there are still many questions about so-called “Long Covid.”
Is there a fair way to distribute limited doses of the vaccine, and who should receive it first?
Once a vaccine is approved by the FDA for Emergency Use Authorization, the CDC must decide how the vaccine will be distributed. The CDC’s Advisory Committee on Immunization Practices (ACIP) had an emergency meeting on December 1, 2020 to finalize their recommendations for Phase 1a distribution of COVID-19 vaccines. Prior to the December meeting, in November, the committee discussed whether the vaccines should be distributed after FDA approval (as opposed to conducting more long-term studies) and who should get the vaccine first.
The National Academies of Science and the CDC agree that healthcare workers should receive the vaccine first. In disaster scenarios, there is a large influx of people needing medical care at once, resulting in shortages of medical professionals, supplies, and facilities. In these scenarios, the typical bioethics protocol changes from helping the most serious cases to mitigating harms. For example, in a normal emergency room setting the more severe patients are handled first followed by the ones that can wait. In a disaster setting, the patients that are easiest to treat are treated first in hopes of getting more people to assist medics with the severe cases. In the case of the SARS-CoV-2 pandemic, healthcare workers are necessarily at risk of being exposed to the virus, but these healthcare workers are needed to treat severe cases. Even though healthcare workers are likely not in the most vulnerable groups (over 65 with co-morbidities), they should receive the vaccine first so there is not a shortage of medical workers. This will result in fewer deaths overall, particularly now that we know more about treating COVID-19. Additionally, one of the ACIP presenters recommended that healthcare workers in the same facility stagger vaccine distribution in case the vaccine’s side effects (fatigue and mild fever) require the healthcare worker to stay home.
The CDC conducted numerical studies to see how many lives would be saved by giving the vaccine to certain populations after healthcare workers receive the vaccine. Their numbers were based on the range of possible effectiveness of the vaccine(s). They found that giving the vaccine to older adults would avert more deaths (1–11% increase in averted deaths) while initially giving the vaccine to essential workers and others at risk of infection would avert the most infections (1–5% increase in averted infections).
But there are several other factors to consider when deciding who should get the vaccine. Younger people, particularly college students, seem to account for the greatest spread, but they are also less likely to suffer from severe complications. A helpful article in the New York Times pointed out that if a vaccine was only 30% effective at blocking infection but could reduce the likelihood of infecting others by 70%, then this vaccine should be given to the group that causes the most spread rather than the most vulnerable to severe COVID-19. Another group found that the vaccine should be given to people over 65 first, unless the vaccine is at least 60% effective and can be distributed to half of the population. In this case, it should be given to people that are more likely to transmit the disease.
This assumes the goals of the vaccine and public health measures are to prevent deaths and severe cases, which are measured by people in the ICU. Minimizing the number of infections or the number of non-ICU hospitalizations might change the decision metrics.
As a sub-group of vulnerable populations, several studies have shown that minorities are disproportionately represented in the ICU, particularly those in Latino and African-American populations. Additionally, those living in long-term care facilities have been disproportionately affected by COVID-19, as well as prisoners and others who are institutionalized. This may mean these subgroups should receive priority over other subgroups of vulnerable populations. As of their December 1 meeting, the ACIP determined that residents in long-term care facilities should be the next priority after healthcare workers.
Vaccine distribution becomes more complicated on the global scale. The U.S., UK, and Canada, for example, have pre-purchased vaccines from Moderna, Pfizer, and AstraZeneca, but poorer countries (i.e., less-resourced countries) do not have the funds to pre-purchase vaccines or the manufacturing infrastructure to produce vaccines. One initiative, COVAX, led by vaccine alliance group Gavi, which partners with the WHO, UNICEF, the World Bank, and the Bill & Melinda Gates Foundation, seeks to provide 2 billion does for low and middle-income countries by the end of 2021.
But not all countries are feeling the effects of the pandemic the same way. For example, Kenya has high infections but not a very high mortality rate. One study indicated that the percentage of the population that has had COVID-19 in Kenya was similar to other countries, but the mortality rate may be lower because the population’s average age is lower. Population demographics might affect prioritizing which countries receive the vaccine first. Additionally, while there is much concern regarding the immediate effects of the pandemic, many poorer countries will suffer from long-term economic effects from the pandemic, another factor that may inform how many vaccines to provide to less-resourced countries.
Update (March 2021): Many states have opened the distribution list to include teachers and people who are 50 and older, and some states have opened the list to all adults. Additionally, people with comorbidities such as diabetes, heart disease, cancer, and obesity were part of the 1B group. Some states have also opened the vaccines to people who smoke ahead of other groups, such as teachers. This has resulted in debates about fairness since smoking is a voluntary habit. However, this brings up a larger question of behavior-induced co-morbidities versus co-morbidities that cannot be helped, such as age.
Global distribution has been slower in some countries. Several European nations have halted distribution of AstraZeneca due to a small number of people developing blood clots. Thus far, it is not conclusive whether the blood clots were due to the AstraZeneca vaccine. Another hurdle in global distribution is the “cold-chain” problem. The two mRNA vaccines, Moderna and Pfizer, require extremely cold temperatures for shipping and storage, which can be prohibitive when sending the vaccine to countries that do not have the facilities for low temperature storage. Adenovirus vaccines, such as AstraZeneca, Johnson & Johnson, and China and Russia’s vaccines, are stable at normal refrigeration temperatures, which may make these vaccines better candidates for global supply. Pfizer has submitted data to the FDA showing that its vaccine can be stored at warmer temperatures that are more commonly found in pharmacy freezers and refrigerators.
Another issue with global distribution is “vaccine diplomacy.” Vaccine diplomacy is the distribution of vaccines from one country to another to garner influence and create diplomatic ties. The major powers competing for global clout with vaccines are the U.S., the UK, India, China, and Russia. All of these countries have vaccines approved by their own regulators. Several of these countries also have vaccines approved by the WHO for emergency use and have contributed vaccines to the COVAX initiative, which seeks to ensure 20% of the populations in the world’s poorest countries have a COVID-19 vaccine by the end of 2021.
However, vaccine diplomacy has also spurned misinformation campaigns, such as Russia intentionally publishing incorrect information about the Pfizer and other vaccines. It has also led to political plays that favor some countries in hopes of securing allies against a common enemy, as in the case of the U.S., Japan, Australia, and India working on a vaccination campaign in Southeast Asia to counter China. But this can also lead to other countries that need vaccines not getting them. Additionally, in a competition to be the first in global vaccine distribution, some countries may short-change their own population or rush to get vaccines out before proper studies have been done.
Will the first vaccine approved by the FDA be the best vaccine, and should vulnerable populations get the first vaccine or the “best” vaccine?
Another consideration that is particularly concerning to bioethicists is whether the first vaccine that will be approved for Emergency Use Authorization will be the best vaccine. There are two issues of concern: 1) how this uncertainty will affect clinical trials for other vaccines, and 2) if the populations that would be getting the first vaccine should wait until they might be able to get a better vaccine.
Before considering these two ethical issues, we need to define what is meant by “best.” In the previous section, a successful vaccine could be one that is at least 50% effective at preventing infection, but a successful vaccine may also be defined as one that prevents spread. The best vaccine may be one that has the best balance of preventing infection and curbing spread.
An article in Science magazine summarizes presentations by the National Institutes of Health bioethics department on the ethical considerations of how the first vaccine would affect subsequent vaccine trials. The presenters pointed out that since there are multiple concurrent Phase 3 clinical trials for the COVID-19 vaccine, clinicians are concerned about the placebo-controlled studies once a vaccine candidate is found. In clinical trials for therapeutics, if a particular therapy is clearly found to be effective during the clinical trial and the control group is a placebo arm, meaning they did not receive an alternative or older treatment, then the placebo arm has a right to know that there is an effective therapy and have the option of taking it.
But the current trials are for a vaccine as opposed to a therapeutic. The participants are healthy individuals who do not have a disease, although they could potentially be infected with it. If a vaccine is found to be more than 50% effective and is approved by the FDA for Emergency Use Authorization, would the placebo arm of the study have a right to know that they were in the placebo group? Should they be given the option to take the vaccine?
Even after a vaccine is approved for emergency use, researchers will continue to study participants in an effort to understand how long the vaccine lasts and whether there are any long-term side effects. Informing the placebo arm that they did not receive the vaccine and giving them the option of taking it would undermine placebo-controlled studies.
Additionally, once a vaccine is approved, this may affect Phase 3 trials of other vaccines. Rather than doing a placebo-controlled double-blind study, research may be required to conduct a non-inferiority trial. This would involve giving half of the participants the vaccine being tested and giving the control arm the vaccine that was approved for emergency authorization. The goal of the clinical trial then becomes to determine whether the tested vaccine performed as well as or better than the authorized one. These trials tend to take longer and are more expensive.
The second ethical issue is related to the question of what groups should be the first to get the vaccine once it is authorized. The minimal efficacy of a vaccine for FDA approval is 50%. Perhaps the first vaccine passed by the FDA prevents COVID-19 in 50% of the people who take the vaccine. The plan is to give this vaccine first to healthcare workers and then to vulnerable populations. But what if the next vaccine is 75% effective? The very populations that would benefit most from having a more effective vaccine ended up with the less effective vaccine of the two. Because these are new pharmaceuticals, the next question would be whether it was safe to give the vulnerable population the more effective vaccine after taking the less effective vaccine. The vaccine will likely not confer life-long immunity given the SARS-CoV-2 mutation rate. It may be that by the time people will require re-vaccination, they can receive a more effective vaccine.
Update: Thus far, the two vaccines that will likely be approved for Emergency Use Authorization by the FDA are Moderna and Pfizer/BioNTech’s. Both of these vaccines have demonstrated greater than 90% efficacy in preventing infection. As far as whether these are the “best” vaccines, that will depend on the goals. These may be the best vaccines for one population, but not for another. For example, the “best” vaccine for younger people might be one that is better at preventing spread, as opposed to preventing infection. It is unclear, as of this writing, whether Moderna and Pfizer/BioNTech’s vaccines prevent person-to-person spread of COVID-19.
The CDC’s Advisory Committee on Immunization Practices (ACIP) released their recommendations for who should be vaccinated in the initial phase of COVID-19 vaccination program on December 1 following an emergency meeting. The committee recommends frontline healthcare personnel and residents of long-term care facilities should be the first to receive the COVID-19 vaccine. They define healthcare personnel as “paid and unpaid persons serving in health care settings who have the potential for direct and indirect exposure to patients or infectious materials.” Long-term care facility residents are people who “reside in facilities that provide a variety of services, including medical and personal care, to persons who are unable to live independently.”
According to Doctor Sara Oliver’s presentation at the ACIP December 1 meeting, one sub-group to consider is female healthcare workers who are pregnant or are recently postpartum. Oliver points out that 75% of the health care workforce are women, but there is no data on mRNA vaccines in pregnant or breastfeeding women.
Update (March 2021): Pfizer, Moderna, and the Johnson & Johnson (J&J) vaccines all seem to be highly effective in preventing severe COVID-19. Preliminary studies show that Pfizer and Moderna likely also prevent spread. J&J most likely does too. This makes sense given what we know of COVID-19 and respiratory viruses in general. Sneezing, coughing, talking, singing, and heavy breathing all increase the number of droplets in the air that could contain viral particles. By diminishing or inhibiting symptoms, such as coughing, this would likely also decrease the level of spread.
Globally, one ongoing concern is the efficacy of China’s CanSino vaccine, which is an adenovirus vaccine. The adenovirus that was used to make the vaccine is one that people might already be immune to because it is the same virus often seen in the common cold. If a person is immune to the particular adenovirus, then the vaccine will be ineffective at preventing COVID-19. [Link to Section on adenoviruses]
Additionally, many people are concerned about viral variants of SARS-CoV-2 that would render the current vaccines less effective. Thus far, the vaccines that have been approved by the U.S. and the UK still show antibody activity against the new variants of SARS-CoV-2. [Link to section on viral variants.] Moderna, Pfizer, and J&J are reportedly working on booster shots in the event a new strain bypasses the immune system’s antibodies against the spike proteins on the virus. The U.S. is monitoring whether people who have already received the vaccine test positive for COVID-19 and whether people are testing positive because of a variant of the virus.
Are people morally obligated to get a COVID-19 vaccine, especially those who have already had the virus or are low-risk for severe disease?
COVID-19 is a new disease, which means researchers are still trying to determine how long immunity lasts after a person has contracted the disease and how contagious the disease is among the population. Both factors are important for considering whether someone is morally obligated to get a vaccine. For example, measles is a highly contagious disease that has a relatively low death rate. But, before a measles vaccine was available and millions of children contracted measles, the low death rate still resulted in hundreds of thousands of deaths. Additionally, measles is so contagious that even when 95% of the population is immunized, as was the case in the early 2000s in the U.S., small outbreaks still occurred. Because of its ability to spread rapidly throughout a community, many countries mandate measles vaccines.
Once a child has had measles, he or she will be immune to the disease. Similarly and in more recent memory, children who have had chickenpox are immune to the varicella zoster virus. Those of us who had chickenpox as a child need not get the varicella vaccine because our bodies have already produced the antibodies to keep us from contracting it again. Having had chickenpox, however, means a person is at risk of getting shingles as an older adult, so there is a vaccine available for older adults to prevent shingles. Today, most states require school children to either get the varicella vaccine or show evidence of immunity.
Analogously, whether a vaccine should be mandated, or if not mandated, whether one is morally obligated to get the COVID-19 vaccine, will depend on how contagious the disease is, how deadly it is, and how long antibodies last in a previously infected person. Unfortunately, because this is a novel virus, researchers are still uncovering the answers to these questions.
Update (March 2021): While researchers are still working on answering these questions, they have found that immunity after contracting COVID-19 seems to last for at least six months. Increasingly, researchers are finding that how contagious COVID-19 is depends on the viral variant as well as whether a person is a superspreader or not.
Studies have gone back-and-forth as to whether the number of antibodies for COVID-19 decreases rapidly after infection or last for several months and what that means for long-term immunity The number of detectable antibodies does not necessarily mean the person has the same risk of getting COVID-19 a second time as he or she did the first time. The CDC has not yet made a recommendation as to whether someone who has had COVID-19 should get a vaccine. According to The Washington Post, the vaccine clinical trials did not exclude people who have already had the virus. The results from these trials may inform scientists on whether a vaccine is necessary for those who have had COVID-19.
Another difficulty is no one knows how many people need to be vaccinated in order to prevent community spread, also known as reaching herd immunity. The number of people that need to be immunized depends not only on how contagious the disease is and how long antibodies last, but also how effective the vaccine is at preventing spread.
Although influenza is a different class of virus than SARS-CoV-2, both viruses cause respiratory diseases. Both viruses can be deadly but are not in the majority of cases. Likely, the moral obligation of getting a SARS-CoV-2 vaccine will be similar to that of getting the flu vaccine, particularly in the future. For now, because the disease is novel and there is understandably much panic surrounding the uncertainty of a new disease, many people feel that there is a stronger moral imperative to get a vaccine at this point in time. However, whether it is unethical to refuse a vaccine might depend on factors that we cannot measure right now as well as a particular person’s situation.
Update (March 2021):
A year after the WHO declared COVID-19 a global pandemic, we have a better understanding of how SARS-CoV-2 transmits from person-to-person as well as which groups of people are most at risk for severe or fatal cases of COVID-19. Many people see taking the vaccine as a moral imperative to end the global pandemic, but it may not be a moral imperative to take the vaccine in later years if COVID-19 remains an endemic disease like the flu. Additionally, although it still has not been verified in formal clinical trials (which tested for symptomatic infection or incidence of severe cases of COVID-19), observational data indicate that the vaccines can curb spread of the disease, not just diminish symptomatic infection.
The goal for both the flu vaccine and the COVID-19 vaccine is to prevent severe cases. In the case of COVID-19, the two largest factors that determine severe cases are age and body mass index, with diabetes and high blood pressure as the most common co-morbidities and access to healthcare another important factor. Those working with the elderly or in the clinical setting may have a moral imperative to get a COVID-19 vaccine, particularly if the person is working with someone who cannot take the vaccine.
Obesity poses a particular conundrum because the CDC estimates some two-thirds of adults in the U.S. are overweight or obese, yet two-thirds of COVID-19 cases do not end up as severe cases. However, a recent study showed that 80% of cases that required hospitalization or resulted in death were among people that were overweight or obese.
Additionally, most people who get COVID-19 will not infect other people. Large-scale infection seems to be driven by superspreading events. Superspreading seems to occur at a certain point in the viral life cycle and depends on other factors such as environment, physical characteristics, and activity. (For a visual illustration of how superspreading works, see here.)
One question is whether children should be required to get a COVID-19 vaccine. Moderna has recently begun clinical trials to test their vaccine in children. Some people believe herd immunity will not be reached unless children are vaccinated; however, young children do not readily spread COVID-19 and are generally not at risk for severe COVID-19. There have been a few cases of Multisystem Inflammatory Syndrome (MIS-C), but the number, thus far, is not high enough to support a blanket requirement for a vaccine, particularly because MIS-C can happen from other viral diseases, not just COVID-19. In the future, COVID-19 vaccination in children may be like the flu vaccine. In most states the flu vaccine is recommended but not required. (See “Whether the government can mandate the COVID-19 vaccine” for more.)
Is there a reason for conscientious objections to certain vaccines based on their development (e.g., tested in fetal cell lines)?
As of this writing, 58 vaccine candidates are undergoing clinical trials (Phases 1–3 and approved for limited use). Not all of these vaccines are developed using the same methods. The broad categories of vaccines are:
- Genetic vaccines
- Viral Vector Vaccines
- Protein-Based Vaccines
- Inactivated or Attenuated Coronavirus Vaccines
- Repurposed Vaccines
The Charlotte Lozier Institute has a helpful tutorial on how the various types of vaccines work.
Vaccine development may use human cell lines that were originally derived from an aborted fetus at some point in the past. These cell lines are perpetual cell lines, meaning once the cell lines were produced from the original fetus, they will continue to actively produce cells. The two cell lines used in some of the COVID-19 vaccine candidates are HEK 293 and PER.C6 cells. The HEK 293 cells are from a female fetus that was aborted in The Netherlands in 1972. The PER.C6 cell line is a proprietary cell line that came from a fetus that was aborted in the 1980s. Most of the vaccines, if they use a human cell line during development, use HEK 293.
(Note: The Lozier Institute has a helpful chart showing which vaccines use these fetal cell lines and at which point in the research and development process they are used, as well as some general information about COVID-19 vaccines.)
For the majority of the vaccines being tested, if human cell lines are used, HEK 293 cells are only used during final testing to confirm antibody production. However, several of the vaccines that use viral vectors to carry DNA into cells use fetal cell lines during the entire development process. Vector-based vaccines for COVID-19 include CanSinBio’s vaccine that was approved for limited use in China and Gamaleya Research Institute’s vaccine that was approved for limited use in Russia. AstraZeneca and Johnson & Johnson’s viral vector vaccines, which are currently in Phase 3 trials, also use human fetal cell lines at all points during development.
Messenger RNA vaccines, which include Moderna’s and BioNTech/Pfizer’s vaccines do not use cell lines during development, but they used HEK 293 cell lines to confirm antibody production. Both of these vaccines are also in Phase 3 trials. NOVAVAX, a protein-based vaccine that is also in Phase 3 trials, uses HEK 293 cells to confirm antibody production. Sinovac and Sinopharm are vaccines made from inactivated or attenuated SARS-CoV-2 virus. They are approved for limited use in China and use HEK 293 cells to confirm antibody production. Other vaccines are in pre-clinical, Phase 1, or Phase 2.
Brendon Foht at The New Atlantis has a helpful article on this topic and provides a brief outline explaining why using fetal cell lines are legal under current regulations on fetal tissue research. CBHD’s forthcoming special report on fetal tissue research will cover the legal history of fetal tissue research in more detail, but Foht’s article is a good summary.
Pertinent to both the legality and the ethics of COVID-19 vaccine development is that this research does not require tissue from newly aborted fetuses. The cell lines are perpetual lines whose origins are morally problematic, but their use is temporally distant.
In the major Christian traditions (Catholic, Protestant, and Orthodox) vaccines, in general, are permissible. Among Christians and those who are pro-life, people differ on whether they consider it morally acceptable to use vaccines made from cells that originally came from an aborted fetus. The Vatican’s statement on vaccines prepared from cells derived from aborted human fetuses permits the use of these vaccines if no other alternatives exist, but it encourages vying for alternatives that come from ethical sources.
One of the reasons for using a standard fetal cell line, such as HEK293, is for consistency. Many of the vaccines being tested use the cell line to confirm the vaccine’s activity. Because prior research has used these cells, they have become the standard for testing whether a vaccine works. For viral vector vaccines, the human cell lines are used to house the viral vectors. Because there is one standard cell line, the same viral vector vaccine can be produced in various parts of the world.
One potential solution, proposed by Foht, is the production of several vaccines, giving people options that would include a vaccine made without the use of fetal cells lines. While having vaccine options would satisfy the personal conscience of vaccine users, it does not address what many see as an endemic problem within vaccine research—the fact that it uses cells from an illicit source.
Several scientists at the Charlotte Lozier Institute propose using fetal cell lines that were obtained from spontaneous miscarriage rather than elective abortion. This would be morally similar to using tissue from a deceased donor, as opposed to tissue procured from a prisoner on death row. While the result is replacing one cell line with another, the means by which the cells were obtained separates the act of killing from therapeutic research.
In many ways, this is similar to the controversy with HeLa cells in biomedical research. The ins-and-outs of how these cells were obtained and the resulting ramifications on the Lacks family are outlined by Rebecca Skloot in her book The Immortal Life of Henrietta Lacks. HeLa cells are an immortal cell line that is now the standard for many studies in biomedical research. However, these cells were obtained from a tumor in Henrietta Lacks after her death from cervical cancer. Neither she nor her family consented to the use of her cells. Researchers are loath to stop using HeLa cells because in order to compare one study to another, they need to use the same cells that prior studies had used.
There are many cases in which prior research or medical practices may not be considered ethical today but were at the time. In the case of obtaining HeLa cells, during the 1950s, informed consent standards for obtaining tissue after death were not the same as they are today. We would consider the original procurement of HeLa cells ethically problematic. The solution is not to completely undo what has been done with HeLa cells, but to first ensure that now cells are obtained with consent (e.g., the Common Rule) and to seek to right the wrong by involving her family in decisions for how the cells are used and providing appropriate compensation.
Similarly, the production of the HEK 293 cell line had unethical origins, although as the scientist who first developed the cell line pointed out, at the time abortions in The Netherlands were only allowed in cases where the mother’s life was at risk, so he assumed that was the circumstance for this tissue. The circumstances surrounding PER.C6 cells are different. This cell line is owned by Crucell and was developed for the sole purpose of industrial production.
We can ensure that fetal tissue from elective abortions is no longer used in research, which is what the recent policies on fetal tissue research intend to do. As far as vaccine development, we can attempt to right this by seeking out other cell lines that can serve the same purpose, whether they are ethically-derived human cell lines or animal models. This does not make people who use vaccines that were tested in fetal cell lines complicit in an immoral act any more so than benefitting from research using HeLa cells does. It does mean, though, that we can seek to do better by pressing for better methods of vaccine production.
Finally, one important question is whether a vaccine for COVID-19 is merited or necessary. Respiratory viruses tend to mutate and therefore a vaccine will likely not confer lifelong immunity. Of the common respiratory viruses, only influenza has a vaccine, and researchers must make a new vaccine every flu season to accommodate the predominant strain of influenza that season. This means we will likely never truly eradicate the SARS-CoV-2 virus, but it will hopefully become less pervasive, like the SARS-CoV virus and the MERS-CoV virus. Most viruses for which we have successful vaccines (either complete eradication or life-long immunity) are “exanthematous” viruses (i.e., skin rashes), such as the ones that cause measles, smallpox, or rubella; neurologic viruses such as the one that causes polio; and hemorrhagic viruses, such as the ones that cause yellow fever or Ebola.
If the vaccine will not confer lifelong immunity and it will not eradicate the disease, then what is the goal? According to infectious disease doctors, the goal is to mitigate the severe cases. This is the same goal as the flu vaccine. The flu vaccine never confers 100% immunity. You can get the flu even if you had the vaccine, but when a large percentage of people get vaccinated for the flu and the vaccine is effective that year, the chances of a vulnerable person getting the flu is much lower.
Unlike the influenza virus, the SARS-CoV-2 virus does not seem to be seasonal. More people spending more time outdoors probably decreases the spread of the virus, but warm or cold weather does not seem to destroy viral particles, given the fact that virus has spread throughout the globe in various climates. The flu, on the other hand, is seasonal, so we get annual flu shots. It is unclear how often one would need to get a COVID-19 vaccine; it may be related to virus’s mutation rate. It is also unclear how long the vaccine will confer some form of immunity since studies are still being done to clarify just how long antibodies remain in the body.
In general, a vaccine will be very helpful in mitigating severe cases as well as curbing community spread. However, a vaccine will most likely not eradicate or give complete immunity to SARS-CoV-2. This means vaccine development is good, but researchers should continue to improve standard care and therapies for COVID-19.
Three vaccines have seen preliminary success in Phase 3 trials. Two are mRNA vaccines: Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 (Moderna worked with the National Institute of Allergy and Infectious Diseases). The third, AstraZeneca’s adenovirus vaccine, has also seen preliminary success, although as of this writing additional studies need to be done to test its efficacy at lower dosages. RNA-based vaccines are new and have never been approved for clinical use, but the way the vaccine works is similar to adenovirus and DNA-based vaccines. All of these vaccines insert genetic material into the cell to produce an immune response against a virus.
By way of review, RNA is a single-strand version of DNA, except the bases designated as T’s in DNA are changed to U’s in RNA. There is also an additional oxygen in the ribose molecules in RNA that are not in DNA. This is why DNA is called “deoxyribonucleic acid” while RNA is just “ribonucleic acid.” That extra oxygen means RNA degrades more easily than DNA. To prevent degradation, RNA-based vaccines must be kept at very low temperatures.
These vaccines refer to mRNA, a certain type of RNA. To understand how mRNA vaccines work, we need to look at how the cell uses naturally-occurring RNA. All of our cells house a huge amount of DNA. Machine-like proteins “unzip” DNA and turn it into RNA. In this process, the proteins make the chemical changes necessary to change T’s to U’s and add that oxygen atom to the RNA backbone. This newly-formed RNA goes through another protein that reads the chemical bases of the RNA strand like a ticker-tape. The bases are essentially a code, or message, that tells the cell how to make a certain protein, hence the name messenger RNA.
Pfizer and Moderna are vaccines that insert synthetic mRNA into cells with a message that tells the cell how to make a piece of the spike protein that sits on the surface of SARS-CoV-2 (for a helpful visualization of this, see this CDC article). The spike protein is how any coronavirus enters cells. (Those spikes surround the surface like a crown, or in Latin corona.) A cell picks up the synthetic mRNA and reads the instructions. The cell responds, not by making the spike protein, but by making a small piece of it. The body sees the piece of the spike protein on the surface of the cell and creates antibodies that will hopefully prevent the actual virus from entering cells in the event that a person is exposed to SARS-CoV-2.
Additionally, because this is RNA and not DNA, the mRNA does not enter the nucleus of the cell and therefore cannot insert itself in our DNA code. It stays outside the nucleus where the proteins are.
While the technology seems new, it is based on years of research beginning in the 1990s when scientists wanted to study mRNA to make immunotherapies. Additionally, researchers knew to go after the spike protein on SARS-CoV-2 from research on the original SARS-CoV virus during and after the pandemic in 2002. The SARS-CoV pandemic was not as widespread as SARS-CoV-2 is, but it did prompt scientists to engage in extensive research on the virus in hopes of preventing any additional outbreaks. In an interview with Dr. Ai Fen, director of the emergency department at Wuhan Central Hospital, she recalls that when she received the first lab results on her patients’ unknown flu-like illness, which would later be identified as COVID-19, the report said “SARS coronavirus.” SARS-CoV and SARS-CoV-2 are distinct viruses, but similar enough that research for one has aided research for the current pandemic.
The biggest ethical concern regarding mRNA vaccines is the long-term effects. Because these vaccines are new, we do not know how they will work long-term. While there is reason to believe the long-term effects would be similar to other genetic-based vaccines, the reality is that these studies have not been done.
The second issue is distribution. Pfizer/BioNTech’s vaccine must be stored at −94°F and Moderna’s at −4°F. Once thawed, Pfizer’s vaccine will last about five days before degrading while Moderna’s vaccine will last up to one month. By way of comparison, AstraZeneca’s adenovirus vaccine, which is made in a similar way to the MMR vaccine, can be stored at 36°F to 46°F and is stable for up to six months. However, AstraZeneca has other ethical issues, mentioned previously.
Overall, even though vaccine development for SARS-CoV-2 has occurred at an incredibly rapid pace, the FDA, the CDC, the National Institutes of Health, as well as the companies involved have made efforts to mitigate harms as much as possible while developing an effective vaccine as quickly as possible. Furthermore, vaccine development happened quickly partly because it builds on many years of work with mRNA therapeutics and coronavirus studies following the SARS-CoV outbreak in 2002 and the MERS-CoV outbreak in 2012.
Update (March 2021):
With any vaccine, or medication, it is important to weigh the risks and the benefits. Millions of people have received either the Moderna or Pfizer vaccine. During that time, a couple of rare side effects have occurred. One is an anaphylactic response. Most people who have an allergic reaction to the vaccine have had an allergic reaction to other vaccines or medications. A component in both the Pfizer and Moderna vaccines, a polyethylene glycol (PEG) derivative, has been known to cause an anaphylactic response on rare occasions. PEG is in other medications and vaccines as well. It is not an active ingredient but is used to stabilize the vaccine. (As one article pointed out, polyethylene glycol is quite different from ethylene glycol, which is the main chemical in antifreeze. It is one of those remarkable things about organic chemistry that a few carbon atoms can make a total difference in how a molecule will act in the body.)
There have been reports in the CDC’s adverse events tracker of a few cases of an autoimmune disorder called thrombocytopenia. This is when the body’s immune system attacks its own platelets in the blood, resulting in poor blood clotting and hemorrhage. Doctors and scientists are not sure whether these incidences of thrombocytopenia are caused by the vaccine or not since the rates of reported thrombocytopenia among the vaccinated population is, thus far, the same as what is found in the normal population. Additionally, doctors are unsure if this condition was latent in the patient prior to vaccination. Thrombocytopenia has been known to occur rarely after receiving other vaccines, such as the MMR vaccine, and it can be a side effect of certain medications. Thrombocytopenia is usually not fatal.
The Johnson & Johnson (J&J) vaccine is an adenovirus-based vaccine that has been granted an emergency use authorization by the U.S. FDA. In the U.S. it showed 72% efficacy; in Latin America it showed 61% efficacy; and in South Africa it showed 64% efficacy. The differences in efficacy are likely because of differences in the prominent viral strains in the respective countries. Notably, when looking at the incidence of severe cases of Covid-19, the J&J vaccine showed 85% efficacy in all regions, meaning the clinical trial group that received the vaccine was 85% less likely to get severe COVID-19 compared to the control group. No deaths were reported in the trial group that had taken the vaccine. Researchers caution against comparing J&J’s efficacy numbers with Moderna and Pfizer because the J&J clinical trial had different goals than the Moderna and Pfizer trials. Also, these vaccines were tested at different points in the pandemic when different viral strains were prominent.
The J&J vaccine was developed in the company’s Belgium lab, Janssen. Janssen has a proprietary method for vaccine development that they used to develop an Ebola vaccine. Janssen is working on vaccines for HIV, RSV, and Zika using the same proprietary technique. Their technique involves the use of Adenovirus 26 (Ad26) and human fetal cell line PER.C6. Just as “coronavirus” describes a general class of viruses, “adenovirus” describes a different class of viruses. Some colds are adenoviruses, and adenoviruses can cause flu-like symptoms.
The J&J vaccine uses the adenovirus to carry a segment of DNA from the SARS-CoV-2 virus that codes for the spike protein. Once the vaccine is injected, the adenovirus transports the DNA segment to the nucleus of a muscle cell where a protein unzips the DNA, converting it to mRNA. This mRNA leaves the cell’s nucleus and enters the cytoplasm where the cell’s machinery translates the mRNA into an amino acid sequences that forms the spike protein. This causes the body to respond by producing antibodies that will target the spike proteins on the SARS-CoV-2 virus. This means when the body encounters SARS-CoV-2 in real life, it will know how to fight the virus, inhibiting it from replicating in the body.
Like the mRNA vaccines, J&J draws on research from SARS-CoV, the original 2002–03 SARS coronavirus. (For a detailed explanation in layman’s terms on how the immune system responds to the spike protein produced by the DNA in the J&J vaccine, see this article in The New York Times: “How the Johnson & Johnson Vaccine Works.” Another good resource is a video on Janssen’s website with an animated explanation of how their vaccine works.)
J&J’s vaccine has a couple of advantages to other COVID-19 vaccines. For one, it requires a single dose, rather than the two-dose regimen that Pfizer, Moderna, and AstraZeneca require. This can help with distribution, particularly in populations where it may be difficult to administer a second dose.
Additionally, the J&J vaccine can be stored for up to three months at standard refrigeration temperatures (36° to 46°F or 2° to 8°C) or for two years in a freezer (−4°F or −20°C). This means the Johnson & Johnson vaccine does not have the “cold-chain” problem that Moderna and Pfizer do, potentially making it a better candidate for global distribution.
One potential downside to the J&J vaccines, and any adenovirus-based vaccine, is some people may have immunity to the adenovirus carrier (also called a vector). If this happens, the immune system attacks the de-activated adenovirus carrier, which inhibits the adenovirus from delivering the DNA that codes for the spike protein in SARS-CoV-2. The Chinese vaccine developed by CanSinoBio and the Russian vaccine from Gamaleya both use an adenovirus strain called Ad5. Because this strain is more common “in the wild,” there is a high probability that many people will be immune to it. The Russian vaccine uses a combination of Ad5 and a less common adenovirus strain in hopes of overcoming the potential pitfalls of immunity. The J&J vaccine uses Ad26, which is a less common adenovirus “in the wild,” and therefore people are less likely to be immune to this vaccine. AstraZeneca uses an adenovirus carrier derived from a chimpanzee in hopes of avoiding any kind of immunity to human adenoviruses.
Although J&J is highly effective as one dose, in November the company announced a second Phase 3 trial to test the efficacy of two doses. The company also launched a trial for pregnant women. As far as safety is concerned, J&J has shown a similar safety profile as Moderna and Pfizer.
One of the ethical issues surrounding the J&J vaccine is the use of an immortal cell line that was originally derived from an aborted fetus. Every vaccine, once it is developed, is tested on immortal cell lines to confirm that it works. Usually these are tested on the HEK293 cell line. The difference with adenovirus vaccines is a human a fetal cell line is used throughout the vaccine production process, not just as a trial once the vaccine is developed. The PER.C6 cell line is a human embryonic retinal cell line that originally came from the retinal tissue of an 18-week-old fetus that was aborted in 1985.
Some see the use of immortal cell lines derived from an aborted fetus as ethically problematic, particularly since there are other options available. Others do not see this as ethically problematic because vaccine development does not involve resupplying the cell lines through recent abortions, and the cells themselves are not the original cells obtained from fetal tissue. See “Is there a reason for conscientious objections to certain vaccines based on their development (e.g., tested in fetal cell lines)?” for more on the use of immortal cell lines derived from aborted fetuses.
Can the U.S. government or private businesses mandate the COVID-19 vaccine?
Vaccine mandates are an ethically contentious topic. Vaccines can help curb the spread of a contagious communicable disease through herd immunity. If a disease is particularly contagious and widespread, a small mortality rate can still result in a large number of deaths. For example, a mortality rate of 0.2% is relatively small, but 0.2% of a billion is still 2 million, and the death rate is different for different populations based on availability of healthcare and other co-morbidities. Measles is a good example. Before 1963 when the measles vaccine became available, nearly every child had measles before reaching age 15. The chance of dying or suffering complications from measles was relatively low, but when 3-to-4 million people in the U.S. contracted measles each year, this amounted to 400-to-500 children dying, 48,000 hospitalizations, and around 1,000 cases of encephalitis each year. The WHO reports that in 2019 around 207,500 people died of measles globally.
The likelihood of dying from COVID-19, given our knowledge of current viral variants, is a fraction of a percent for some demographics, such as people under 60, but much higher for people who are over 60, male, obese, or have other underlying health conditions. Additionally, because this is a new disease, people do not have immunity or even partial immunity from previous infections in the same way they do with the annual flu. This situation is changing as more people have had COVID-19 or are getting the vaccine. Recent reports show a marked decrease in hospitalizations and deaths, particularly among the most vulnerable group—the institutionalized elderly. This is likely due to vaccination efforts.
A Viewpoint article in JAMA outlines the reasons why a SARS-CoV-2 vaccine mandate might be appropriate in limited cases but would likely be counterproductive as a population-wide mandate.  The vaccine may be required for situations where people are at higher risk of contracting or spreading COVID-19, such as college and university settings or healthcare settings. While there is precedent for state-mandated vaccinations for children attending school, there are several hurdles before the vaccine for COVID-19 is added to the list of childhood immunizations. It will likely be analogous to the flu vaccine, which is encouraged but not required in most states, except Massachusetts.
For additional resources on childhood vaccinations, see CBHD’s article “Should Children Be Routinely Immunized?” by Dr. Ferdinand D. Yates, Jr.
Several countries have considered using vaccine passports when people travel within the country or come into the country. Additionally, many countries are considering whether vaccine passports or certificates should be used for events and social gatherings. In the European Union, for example, the European Council has approved a Digital Green Certificate that provides information on a person’s medical status regarding COVID-19. Specifically, it would indicate whether a person has received a vaccine, had a recent negative PCR test, or had COVID-19. The council specifies that this would merely provide factual information about an individual’s health status; it is up to the individual European countries to decide what policies would be implemented.
Israel has implemented its own “green passport” allowing people who have been vaccinated to go to restaurants or pubs. In the U.S., a certification of vaccination might be required to go to certain places and legally employers are allowed to require vaccination so long as exemptions are made for disability and religion.
Several airlines want to implement a vaccine certification program to allow for safe air travel. The International Air Transport Association, the trade group for global airlines, and IBM are working on digital health passes based on blockchain technology to ensure data security. The World Economic Forum and the Commons Project Foundation are also working on a digital vaccine passport.
Requiring certain vaccinations to enter a country is not new. Many countries require a yellow fever vaccine, for example. However, there is little to no legal precedent for statewide restrictions and digital screening. Other concerns are risks of hackers obtaining digital health information. Digital passports will need to be secure enough to prevent this, but also transferable so they can be used among various countries. Additionally, there have already been reports of a black market for forged vaccine certificates, fake negative PCR results, and even doses of a vaccine on the dark web.
Discrimination between those who have been vaccinated and those who have not, either by choice, for medical reasons, or because of limited supply in their country, is one of the biggest concerns among bioethicists. In the near-term, the people who will be able to travel are people who are middle-age and older from wealthy countries. Over the next year, there may be a two-tiered system of those from wealthy countries versus those from poorer countries. This tiered system might also be between those who do not have smartphones versus those who do. (The European Council has proposed using both paper and digital QR codes to help with this.)
Another issue is the difference in vaccine approval in different countries. If a person who has been vaccinated with a vaccine that is not approved in the country to which they wish to travel, then they may not be able to enter that country. Travel may be eased or restricted based on vaccine nationalism. For example, China will place fewer visa restrictions on people who have had one of China’s vaccines.
Most countries will likely require some proof of vaccination or immunity as vaccinations continue and more businesses open. Many people are concerned that discrimination based on health status may become a norm. In response to this concern, the European Council has called for the Digital Green Certificate to be a temporary document until the WHO has declared the pandemic over.
Viruses are made of genetic material that codes for all the components of a virus, including the protein surface that is recognized by our immune system. When the virus’s genetic code changes, that is called a mutation. Different viruses mutate at different rates. Influenza, for example, mutates at a fast rate. This is why we have to get a new flu vaccine every year and why people can sometimes get the flu twice in one season or get the flu even if they have been vaccinated. The SARS-CoV-2 virus mutates about once every two weeks, which is half the mutation rate of influenza and one-quarter the rate of HIV. Compared to other RNA-based viruses, it is relatively stable.
When a virus mutates, it creates a new variant. “Variant” and “strain” are often used interchangeably, although they are technically different. Strains refer to organisms, such as bacteria. Viruses are not alive, and they are not organisms, so we should probably use the term “variant” and describe “viral variants” and “bacterial strains.” This wording is not strictly adhered to in media outlets. (Note: Because viruses are not alive, we also should not say that a virus “dies.” Instead, it “degrades.”)
The CDC defines a SARS-CoV-2 variant as having one or more mutations that differentiate it from other variants that are circulating in a population. Variants are classified as variant of interest, variant of concern, and variant of high consequence. There are currently no SARS-CoV-2 variants that are classified as “variant of high consequence,” which would constitute a public health emergency. A variant is considered to be of high consequence if it would not be detectable using diagnostic tools, current vaccines are severely limited or ineffective toward this variant, approved therapeutics do not work against this variant, or the variant results in more severe cases and hospitalizations. A variant of concern, in contrast, is detectable using current diagnostic tools, although current tools may give more false positives or false negatives, than prior variants. Current therapies and vaccines may not work as well against a variant of concern, but they are not rendered ineffective. Variants of concern may be more transmissible and may cause more severe cases. 
There are several variants of concern circulating globally, although they tend to be concentrated in certain regions. All but one of the variants of concern appear to be more transmissible, meaning they tend to spread more easily between people. One of the variants, B.1.1.7 out of the UK, also likely leads to more severe cases. The currently approved vaccines are still effective against these variants of concern, although lab tests show that they are not as effective at neutralizing some of these variants as they were against older ones.
There are several variants of interest. These variants have mutations in parts of the SARS-CoV-2 genome that may affect its transmissibility. These are “of interest” because they may become a variant of concern.
The CDC has a section of its website that is kept up to date on recent coronavirus variants.
 See CBHD Staff, “Coronavirus: Explanations and Ethical Issues,” The Center for Bioethics & Human Dignity, March 23, 2020, https://cbhd.org/content/coronavirus-explanations-and-ethical-issues.
 Carl Zimmer, Jonathan Corum, and Sui-Lee Wee, “Coronavirus Vaccine Tracker,” New York Times, November 30, 2020, https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html.
 Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”
 Heather Zeiger, “China: Rewriting the History of COVID-19,” Mind Matters News, March 19, 2020, https://mindmatters.ai/2020/03/china-rewriting-the-history-of-covid-19/.
 Michael R. Gordon and Dustin Volz, “Russian Disinformation Campaign Aims to Undermine Confidence in Pfizer, Other Covid-19 Vaccines, U.S. Officials Say” The Wall Street Journal, March 07, 2021, https://www.wsj.com/articles/russian-disinformation-campaign-aims-to-undermine-confidence-in-pfizer-other-covid-19-vaccines-u-s-officials-say-11615129200.
 Heather Zeiger, “Charges Reveal Extent of China-Sponsored Hacking in the West,” Mind Matters News, July 30, 2020, https://mindmatters.ai/2020/07/charges-reveal-extent-of-china-sponsored-hacking-in-the-west/.
 Carl Zimmer, “‘This Is All Beyond Stupid.’ Experts Worry about Russia’s Rushed Vaccine,” New York Times, August 11, 2020, https://www.nytimes.com/2020/08/11/health/russia-covid-19-vaccine-safety.html; Jon Cohen, “Russia’s Claim of a Successful COVID-19 Vaccine Doesn’t Pass the ‘Smell Test,’ Critics Say,” Science, November 11, 2020, https://www.sciencemag.org/news/2020/11/russia-s-claim-successful-covid-19-vaccine-doesn-t-pass-smell-test-critics-say.
 Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”
 U.S. Food & Drug Administration, “Step 3: Clinical Research,” fda.gov, January 4, 2018, https://www.fda.gov/patients/drug-development-process/step-3-clinical-research.
 CDC, “CDC COVID Data Tracker,” CDC.gov, accessed November 11, 2020, https://covid.cdc.gov/covid-data-tracker/#demographics.
 Roni Caryn Rabin, “Death Rates Have Dropped for Seriously Ill Covid Patients,” The New York Times, October 29, 2020, https://www.nytimes.com/2020/10/29/health/Covid-survival-rates.html
 Denis Y. Logunov et al., “Safety and Efficacy of an rAd26 and rAd5 Vector Based Heterologous Prime-Boost COVID-19 Vaccine: An Interim Analysis of a Randomised Controlled Phase 3 Trial in Russia,” The Lancet 397, no. 10275 (2021): 671–81, https://doi.org/10.1016/S0140-6736(21)00234-8.
 Reuters Staff, “China’s CanSino Says Gets Green Light to Continue Phase III Trials” Reuters, January 31, 2021, https://www.reuters.com/article/us-health-coronavirus-vaccine-cansinobio-idUSKBN2A111W.
 Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”
 Sarah Zhang, “The Vaccine News That Really Matters,” The Atlantic, October 19, 2020,
 Zhang, “The Vaccine News That Really Matters.”
 Matthew W. McCarthy, David Oshinsky, and Arthur Caplan, “Make Pre-Approval Covid-19 Vaccines Available Through Expanded Access, Not an EUA,” STAT News, November 9, 2020, https://www.statnews.com/2020/11/09/expanded-access-not-eua-for-distributing-preapproval-covid-19-vaccines/; Clint Hermes, “Covid-19 Vaccines Shouldn’t Get Emergency-Use Authorization,” MIT Technology Review, November 13, 2020, https://www.technologyreview.com/2020/11/13/1012098/covid-19-vaccines-fda-emergency-use-authorization-opinion/.
 U.S. Food & Drug Administration, “Expanded Access: Information for Patients,” fda.gov, May 20, 2019, https://www.fda.gov/news-events/expanded-access/expanded-access-information-patients.
 Helen Branswell, “FDA Shows Signs of Cold Feet over Emergency Authorization of Covid-19 Vaccines,” STAT News, October 23, 2020, https://www.statnews.com/2020/10/23/fda-shows-signs-of-cold-feet-over-emergency-authorization-of-covid-19-vaccines/.
 Smriti Mallapaty, “Can COVID Vaccines Stop Transmission? Scientists Race to Find Answers,” Nature, February 19, 2021, https://www.nature.com/articles/d41586-021-00450-z.
 Diane Gbesemete et al., “Exploring the Acceptability of Controlled Human Infection with SARSCoV2—a public consultation,” BMC Medicine 18, no. 209 (2020): https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01670-2.
 Rob Lambkin‐Williams and John P. DeVincenzo, “A COVID-19 Human Viral Challenge Model: Learning from Experience,” Influenza and Other Respiratory Viruses 14, no. 6 (2020): https://doi.org/10.1111/irv.12797.
 Tony Kirby, “COVID-19 Human Challenge Studies in the UK,” The Lancet Respiratory Medicine, October 30, 2020, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30518-X/fulltext.
 Alicia Ault, “COVID-19 Vaccine Should Go to HCWs First, NAS Panel Says,” Medscape, October 2, 2020, https://www.medscape.com/viewarticle/938514; Young, “CDC Panel Takes on COVID Vaccine Rollout, Risks, and Side Effects.”
 See Donal P. O’Mathuma, Vilius Dranseika, and Bert Gordijn, eds., Disasters: Core Concepts and Ethical Theories (Springer Open, 2018).
 Sara Oliver, “Clinical Consideration for Populations Included in Phase 1a,” in “ACIP Presentation Slides: December 2020 Meeting,” by Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention, December 1, 2020, https://www.cdc.gov/vaccines/acip/meetings/slides-2020-12.html (PDF available for download).
 “Young, “CDC Panel Takes on COVID Vaccine Rollout, Risks, and Side Effects.”
 Kim Tingley, “Who Should Get a Covid-19 Vaccine First?” The New York Times, November 5, 2020, https://www.nytimes.com/2020/11/05/magazine/who-gets-covid-vaccine.html.
 Jazmyn T. Moore, “Disparities in Incidence of COVID-19 Among Underrepresented Racial/Ethnic Groups in Counties Identified as Hotspots During June 5–18, 2020 — 22 States, February–June 2020,” Morbidity and Mortality Weekly Report 69, no. 33 (2020): 1122–26, https://www.doi.org/10.15585/mmwr.mm6933e1.
 “Gavi, “COVAX,” accessed November 30, 2020, https://www.gavi.org/covax-facility; Rebecca Randall, “Christians Ready to Help COVID-19 Vaccine Go to Neediest First,” Christianity Today, November 17, 2020, https://www.christianitytoday.com/news/2020/november/christian-covid-vaccine-ethical-global-distribution.html.
 Bob Yirka, “Exploring the Reasons Behind Kenya’s Low COVID-19 Infection and Death Rates,” Medical Xpress, November 13, 2020, https://medicalxpress.com/news/2020-11-exploring-kenya-covid-infection-death.html.
 Homi Kharas “The Impact of COVID-19 on Global Extreme Poverty,” Brookings Institute, October 21, 2020, https://www.brookings.edu/blog/future-development/2020/10/21/the-impact-of-covid-19-on-global-extreme-poverty/.
 Mike Catalini, “EXPLAINER: Why Expansion of Vaccine to Smokers Caused a Stir,” Medical Xpress, January 16, 2021, https://medicalxpress.com/news/2021-01-expansion-vaccine-smokers.html.
 Reuters Staff, “AstraZeneca Finds No Evidence of Increased Blood Clot Risk from Vaccine,” Reuters, March 14, 2021, https://www.reuters.com/article/uk-health-coronavirus-astrazeneca-vaccin-idUSKBN2B60L6.
 “Pfizer and BioNTech Submit COVID-19 Vaccine Stability Data at Standard Freezer Temperature to the U.S. FDA,” Pfizer Press Release, February 19, 2021, https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-submit-covid-19-vaccine-stability-data.
 WHO, “COVAX: Working for Global Equitable Access to COVID-19 Vaccines,” WHO.int, accessed March 26, 2021, https://www.who.int/initiatives/act-accelerator/covax.
 Michael Gordon and Dustin Volz, “Russian Disinformation Campaign Aims to Undermine Confidence in Pfizer, Other Covid-19 Vaccines, U.S. Officials Say,” The Wall Street Journal, March 07, 2021, https://www.wsj.com/articles/russian-disinformation-campaign-aims-to-undermine-confidence-in-pfizer-other-covid-19-vaccines-u-s-officials-say-11615129200.
 See “Vaccine Diplomacy: China and SinoPharm in Africa,” The Council on Foreign Relations, January 6, 2021, https://www.cfr.org/blog/vaccine-diplomacy-china-and-sinopharm-africa; Ryan Heath, “Vaccine Diplomacy: Asia Flooded, Africa Deserted,” Politico, March 12, 2021, https://www.politico.com/newsletters/global-translations/2021/03/12/vaccine-bombshell-day-492092; Huizhong Wu And Kristen Gelineau, “Chinese Vaccines Sweep Much of the World, Despite Concerns,” Associated Press, March 2, 2021, https://apnews.com/article/technology-chile-diplomacy-coronavirus-pandemic-covid-19-pandemic-16482e2ad022975bebaa502415499b08.
 Jon Cohen, “First Vaccine May Stymie Hunt for Better Ones,” Science, October 23, 2020, https://science.sciencemag.org/content/370/6515/389.
 See Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research, “Guidance Document: Non-Inferiority Clinical Trials,” U.S. FDA, November 2016, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/non-inferiority-clinical-trials.
 CDC, “Advisory Committee on Immunization Practices.”
 Oliver, “Clinical Consideration for Populations Included in Phase 1a.”
 CDC, “SARS-CoV-2 Variant Classifications and Definitions,” CDC.gov, updated March 24, 2021, https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html.
 Julie Steenhuysen, “US Plans to Use Real World Data to Determine When Vaccines Need to Be Updated,” Medscape (republished from Reuters), March 18, 2021, https://www.medscape.com/viewarticle/947626. See also Peter Loftus and Jared S. Hopkins, “Covid-19 Vaccine Makers Take Aim at Dangerous New Strains,” The Wall Street Journal, February 03, 2021, https://www.wsj.com/articles/covid-19-vaccine-makers-take-aim-at-dangerous-new-strains-11612357201.
 WHO, “Measles” Fact Sheet, WHO.int, December 5, 2019, https://www.who.int/news-room/fact-sheets/detail/measles.
 CDC, “Immunization Schedules,” CDC.gov, February 3, 2020, https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html.
 Rebecca J. Cox and Karl A. Brokstad, “Not Just Antibodies: B Cells and T Cells Mediate Immunity to COVID-19,” Nature Reviews Immunity 20 (2020): 581–82, https://doi.org/10.1038/s41577-020-00436-4.
 CDC, “Frequently Asked Questions about COVID-19 Vaccination” CDC.gov, November 24, 2020, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/faq.html.
 Carolyn Y. Johnson and Aaron Steckelberg, “What You Need to Know about the AstraZeneca, Moderna, and Pfizer Vaccines,” The Washington Post, November 30, 2020, https://www.washingtonpost.com/health/2020/11/17/covid-vaccines-what-you-need-to-know/.
 Mallapaty, “Can COVID Vaccines Stop Transmission?”
 Lyudmyla Kompaniyets et al., “Body Mass Index and Risk for COVID-19—Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death—United States, March–December 2020,” Morbidity and Mortality Weekly Report, CDC.gov, March 12, 2021, https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e4.htm.
 Dyani Lewis, “Superspreading Drives the COVID Pandemic—And Could Help to Tame It,” Nature, February 23, 2021, https://www.nature.com/articles/d41586-021-00460-x.
 CDC, “For Parents: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19,” CDC.gov, updated February 24, 2021, https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/mis-c.html.
 Zimmer, Corum, and Wee, “Coronavirus Vaccine Tracker.”
 Jonathan Corum, Knvul Sheikh, and Carl Zimmer, “Different Approaches to a Coronavirus Vaccine,” New York Times, May 20, 2020, https://www.nytimes.com/interactive/2020/05/20/science/coronavirus-vaccine-development.html.
 Brendan Foht, “Abortion and the Coronavirus Vaccine: Why We Need an Option That Will Be Morally Acceptable to All Americans,” The New Atlantis, June 8, 2020, https://www.thenewatlantis.com/publications/abortion-and-the-coronavirus-vaccine.
 Ivan Couronne, “How Fetal Cells from the 1970s Power Medical Innovation Today,” Medical Express, October 20, 2020, https://medicalxpress.com/news/2020-10-fetal-cells-1970s-power-medical.html.
 Charlotte Lozier Institute, “Use of Aborted Fetal Tissue: Questions & Answers,” June 5, 2019, https://lozierinstitute.org/use-of-aborted-fetal-tissue-questions-answers/, Q4(b): “Are there alternatives to use of aborted fetal tissue in research? There are many alternatives. One is use of miscarried tissue, which can be used to study development as well as causes of pregnancy loss.”
 Rebekah Skloot, The Immortal Life of Henrietta Lacks (New York: Broadway Paperbacks, 2011).
 The Common Rule is the U.S. Federal Policy for the protection of human subjects and is influenced by the Belmont Report. The Common Rule was published in 1991 and then revised in 2018 to include guidelines for research with human tissue and using genetic information. This policy informs institutional review boards on whether to approve research involving human subjects or human materials. See U.S. Department of Health & Human Services, “Federal Policy for the Protection of Human Subjects (‘Common Rule’),” HHS.gov, March 18, 2016, https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html.
 Sarah Zhang, “A Vaccine Reality Check,” The Atlantic, July 24, 2020, https://www.theatlantic.com/health/archive/2020/07/covid-19-vaccine-reality-check/614566/.
 CDC, “How COVID-19 Spreads,” CDC.gov, October 28, 2020, https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html.
 Reuters Staff, “AstraZeneca CEO Expects to Run New Global Trial of COVID-19 Vaccine: Bloomberg,” Reuters, November 26, 2020, https://www.reuters.com/article/us-health-coronavirus-astrazeneca/astrazeneca-ceo-expects-to-run-new-global-trial-of-covid-19-vaccine-bloomberg-idUSKBN28620H.
 Abbasi, “COVID-19 and mRNA Vaccines.”
 CDC, “Understanding mRNA COVID-19 Vaccines,” CDC.gov, updated March 4, 2021, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html.
 Lily Kuo, “Coronavirus: Wuhan Doctor Speaks Out against Authorities,” The Guardian, March 11, 2020, https://www.theguardian.com/world/2020/mar/11/coronavirus-wuhan-doctor-ai-fen-speaks-out-against-authorities.
 Charlotte Lozier Institute, “Use of Aborted Fetal Tissue: Questions & Answers.”
 About 3.3 per 100,000 adults per year are diagnosed with immune thrombocytopenia. See National Organization for Rare Disorders (NORD), “Immune Thrombocytopenia” Rare Disease Database, RareDiseases.org, updated 2019, https://rarediseases.org/rare-diseases/immune-thrombocytopenia/.
 Mayo Clinic Staff, “Thrombocytopenia (Low Platelet Count),” Mayo Clinic, April 8, 2020, https://www.mayoclinic.org/diseases-conditions/thrombocytopenia/symptoms-causes/syc-20378293.
 For the Covid-19 vaccines, vaccine efficacy is the percent reduction of symptomatic or severe cases of COVID-19 in a clinical trial compared to the control group. A vaccine with 72% efficacy does NOT mean that out of 100 people who received the vaccine, 72 will not get COVID-19 and 28 will. It means the person’s chances of getting symptomatic or severe COVID-19 is 72% less than it was before.
 “Coronavirus Vaccine Tracker” The New York Times, Updated March 11, 2021, https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html.
 Matthew Herper and Helen Branswell, “FDA Scientists Endorse J&J’s Covid Vaccine, as New Data Shed Light on Efficacy,” STAT News, February 24, 2021, https://www.statnews.com/2021/02/24/new-data-shed-light-on-efficacy-of-jjs-single-dose-vaccine-against-covid-19/.
 For details on the J&J clinical trial see Johnson & Johnson, “About Our ENSAMBLE Studies,” jnj.com, accessed March 11, 2021, https://www.jnj.com/coronavirus/about-phase-3-study-of-our-covid-19-vaccine-candidate.
 Jonathan Corum and Carl Zimmer, “How the Johnson & Johnson Vaccine Works” The New York Times, March 5, 2021, https://www.nytimes.com/interactive/2020/health/johnson-johnson-covid-19-vaccine.html.
 Allison Martell and Julie Steenhuysen, “Scientists See Downsides to Top COVID-19 Vaccines from Russia, China,” Reuters, August 31, 2020, https://www.reuters.com/article/us-health-coronavirus-vaccines-adenoviru-idUSKBN25R19H.
 “Coronavirus Vaccine Tracker”
 Charlotte Lozier Institute, “CLI Statement on Johnson & Johnson Vaccine: Abortion-Derived Cell Lines Used in Production Process,” LozierInstitute.org, March 3, 2021, https://lozierinstitute.org/cli-statement-on-johnson-johnson-vaccine-abortion-derived-cell-lines-used-in-production-process/.
 WHO, “Worldwide Measles Deaths Climb 50% from 2016 to 2019 Claiming over 207 500 Lives in 2019,” WHO.int, November 12, 2020, https://www.who.int/news/item/12-11-2020-worldwide-measles-deaths-climb-50-from-2016-to-2019-claiming-over-207-500-lives-in-2019.
 “COVID-19 Nursing Home Data” Data.CMS.gov, March 14, 2021, https://data.cms.gov/stories/s/COVID-19-Nursing-Home-Data/bkwz-xpvg/.
 “State-by-State: Vaccinations Required for Public School Kindergarten,” ProCon.org, updated August 8, 2020, https://vaccines.procon.org/state-by-state-vaccinations-required-for-public-school-kindergarten/.
 For an explanation of PCR testing, see Cleveland Clinic, “COVID-19 and PCR Testing,” ClevelandClinic.org, November 20, 2020, https://my.clevelandclinic.org/health/diagnostics/21462-covid-19-and-pcr-testing.
 Emily N. Litzinger and Alexa R. Hanlon, “Digital Vaccine Passports and the Legal Risks for Employers,” Corporate Counsel, March 24, 2021, https://www.law.com/corpcounsel/2021/03/24/digital-vaccine-passports-and-the-legal-risks-for-employers/.
 David Koenig, “EXPLAINER: Will You Need a ‘Vaccine Passport’ to Travel?” Associated Press, March 18, 2021, https://apnews.com/article/technology-travel-pandemics-europe-airlines-9c410bacd04c443f4ed562d1b2c3d37e.
 Litzinger and Hanlon, “Digital Vaccine Passports and the Legal Risks for Employers.”
 Tim De Chant, “Dark Web Bursting with COVID-19 Vaccines, Vaccine Passports” Ars Technica, March 23, 2021, https://arstechnica.com/tech-policy/2021/03/dark-web-bursting-with-covid-19-vaccines-vaccine-passports/.
 Reuters Staff, “China Eases Visa Rules for Recipients of Its Vaccines,” Reuters, March 15, 2021, https://www.reuters.com/article/us-health-coronavirus-china-vaccine/china-eases-visa-rules-for-recipients-of-its-vaccines-idUSKBN2B71XM.
 Ewen Callaway “The Coronavirus IS Mutating—Does It Matter?” Nature, September 8, 2020, https://www.nature.com/articles/d41586-020-02544-6.
 CDC, “SARS-CoV-2 Variant Classifications and Definitions,” CDC.gov, updated March 24, 2021, https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html.
Last updated March 29, 2021