Written by Rahil Samlal and Kinjaal Nagindas
While the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), has been felt globally, there remains much confusion surrounding deeper aspects of how the virus replicates, where it came from, how it causes symptoms, and finally, what our best strategies are in combating it. Since it was given pandemic status in March 2020 by the World Health Organisation (WHO), even till now, almost ten months later, there seems to be more questions than answers - as is the nature with novel viruses. With the rise in cases and death toll during the second wave which has swept nations worldwide, a vaccine is likely the best candidate in our arsenal of defence against the virus, and many think this would allow the world to get back to a ‘slightly-more-normal’ place, if such a place is even possible. One would not be surprised that there is a cloud of differing opinions surrounding vaccine development and its impacts.
The aim is to discuss the ethical considerations surrounding these opinions and facts to hopefully unjumble the mass thread of hysteria and misinformation often attached to vaccines and what they are made of.
Additionally, the article will discuss different prophylactic treatment options like the use of convalescent plasma as well as the antiviral drug remdesivir.
How did we get here?
On the 31st of December 2019, the WHO country Office in the People’s Republic of China (PRC) had picked up on a media statement which was made by the Wuhan Municipal Health Commission. This was from their website which documented cases of viral pneumonia outbreaks in Wuhan, PRC, of which the cause was unknown. In January of 2020, the world would know the disease responsible as COVID-19 caused by the novel SARS-CoV-2, and cases were concentrated in Wuhan, but it would be spreading rapidly both in and out of the PRC with reports of people dying from the disease as early as January and February 2020 in the United States, which was later confirmed.
What are the origins of SARS-CoV-2?
SARS-CoV-2 is a virus in the subfamily Coronaviridae. Looking at phylogenetic relationships, the subfamily can be split into four distinct genera: α-, β-, γ-, and δ-CoV. What is of concern to humans are the members of the α- and β-CoVs. These viral particles have a positive-sense single stranded RNA surrounded by a lipid envelope (this is a key aspect to the infectious cycle within host cells), and this has the ability to cause an array of diseases related to the enteric, hepatic, respiratory, and neurological systems in both mammals and birds. Presently, two coronaviruses are spreading within humans, two α-CoVs (229E and NL63) and two β-CoVs (OC43 and HKU1) which cause symptoms overlapping with the common cold.
At the time of writing this article, bats are considered to be the natural hosts for the Middle Eastern respiratory syndrome coronavirus (MERS-CoV) as well as for SARS-Cov-2. Bats are the reservoir for many types of viruses including many coronaviruses and they are progenitors for highly pathogenic strains which spill over to human populations usually through an intermediate host of animal origin.
How does SARS-CoV-2 spread and cause symptoms?
In accordance with COVID-19 regulations, the spread of the virus is largely due to respiratory contact, thus the Centers for Disease Control and Prevention (CDC) recommend steps to limit contact and decrease the spread. SARS-CoV-2 (2019-present), like its predecessor SARS-CoV-1 (2002-2003), uses human angiotensin-converting enzyme 2 (ACE2) as a receptor to gain entry into cells. ACE-2 receptors are mainly expressed and found in large numbers in the lungs, heart, intestines, and kidneys - this information aided researchers in explaining the symptoms which the virus causes. Under normal circumstances, ACE-2 serves a biologically important role by promoting the cleavage of certain peptide hormones (angiotensin I and II) which are involved in the homeostasis of blood pressure.
The clinical features of the disease hosts a wide range of signs and symptoms spanning many different organs. These include the manifestations of respiratory diseases like hypoxemia and dyspnoea; impairment of the kidneys with a reduced urine output, tachycardia, coagulation dysfunction, as well as altered mental status. Previously stated are on the more severe end of symptoms and are likely to be experienced in patients with comorbidities and secondary infections. The most common symptoms remain as dry cough, high fever, and tiredness along with aches and pains and loss of tastes and/or smell amongst others.
When thinking about combating viral diseases, be it epidemic or pandemic in nature, the first line of active defence is wanting to confer immunity into the population. This is done with the use of vaccines, which usually take anywhere between 10-15 years to make, including the research and development phases, for combating a worldwide or localized pandemic. However, the COVID-19 vaccine from Moderna and Pfizer has been made in under a year. This can be attributed to many reasons.
Firstly, the vaccines made by companies Moderna and Pfizer are not what we usually expect from vaccines. The purpose of them remains to make those who get them immune from the virus by creating antibodies within the body, however instead of using an altered or non-harmful form of the virus, their vaccine is an mRNA vaccine. Subsequently, the vaccine does not contain any SARS-Cov-2 particles.
It simply contains the instructions for your body’s cells to create the spike proteins found on the outer membrane of the virus, thus initiating the immune response to create antibodies against the virus.
The proteins which are made inside the body are harmless, and effective in eliciting an immune response. Since the mRNA never enters the nucleus of cells (where the host DNA is stored), there is little to no evidence that the vaccine is able to ‘edit the genome’ of its host.
With a worldwide response and many committees and organisations being formed in aiding the fight against this pandemic, there is a huge financial input for research and development of a global vaccine.
The other types of vaccines are being made; one being developed by Johnsons & Johnsons (J&J) taking centre stage at the end of January 2021 as they release their full study results. The purpose of the J&J vaccine is simi of Moderna and Pfizer, however the delivery system of the SARS-CoV-2 genetic material is starkly different. Using a gutted adenovirus as the viral vector to hold the genetic material of the SARS-CoV-2 virus, this vaccine used double stranded DNA instead of single stranded mRNA. The Adenovirus would enter the host cell upon vaccination and inject the double stranded DNA into the host cytoplasm, where viral mRNA will be made and translated into spike proteins. These spike proteins will present themselves on the surface of vaccinated cells and the immune system will take over from there, where antigen-presenting cells will pick up the spike protein and present it to helper T-cells, which will in turn initiate the B-cells to flourish and produce antibodies.
The concept of vaccinations are highly controversial for many, heavily debated and yet effective, this medical innovation proves to create several problems. Essentially, as time progressed since the start of the COVID-19 pandemic, scientists and companies around the world searched and tested for an effective COVID-19 vaccine. However, the response to establishing this vaccination as a probable solution to the pandemic was not well received by certain individuals. The idea behind vaccine introduction would lead to creating herd immunity within any given population. This novel virus seemed to have posed serious health issues for several individuals across various demographics, although some healthy individuals were able to overcome the symptoms thus resulting in acquired immunity to the virus, those who were immunocompromised were highly affected, thus vaccinating such individuals would aid in reaching the herd immunity threshold.
The idea of medically certified vaccinations being a cause for concern may not be backed with much scientific data however a certain hesitancy and resistance is present within many individuals. It is then essential that the views and opinions of others are respected as without the consideration of human rights, an ethical dilemma is created.
On the contrary, if no vaccination is administered with regards to SARS-CoV-2 achieving herd immunity would therefore create an ethical dilemma as the majority of the global population seem highly susceptible to the effects of the virus. Consequently, the health and safety of individuals is essentially compromised. The situation is indicative of the ethics in which society perceives human rights and public safety. Furthermore, there are 4 key debate topics to discuss with regards to vaccine ethics:
Informed consent: Throughout history, there have been unethical incidences where individuals from lower socio-economic communities are subjected to clinical vaccination trials without seeking prior consent from the participants. This is not only unethical but also would be in violation of human rights. Those who manage these experimental pharmaceuticals are in a position of power in areas of poverty as the individuals see the experimental treatment as a solution and not a choice. On the contrary, would hospitals and medical facilities need to receive consent from health care personnel when administering the vaccination. Due to the limitation in the SARS-CoV-2 vaccine access, the Advisory Committee for Immunization Practices (ACIP), suggests that the first round of vaccination should be administered to health care personnel, would it be unethical to make this vaccination mandatory for these individuals? Although receiving the vaccine for this group of individuals would serve an essential role in combatting the pandemic, one should also consider the human rights of the health care workers, yet an ethical dilemma is created if they refuse to be vaccinated as they may not only put themselves but others at risk of COVID-19. How can officials protect their human rights and yet protect those individuals who are vulnerable to the virus and its effects?
Testing and research: Additionally, for a vaccine to be tested along all boards, testing needed to have been carried out along various demographics of the globe's population. Due to the current social issues around racial conflicts in recent days, would suggesting such testing be considered unethical and inconsiderate? Sufficient information would need to be provided as to why it is imperative for a vaccination to be tested across several demographics. Additionally, when testing various demographic groups, the understanding and full comprehension of consent, side effects and ability to withdraw at any moment from the trial needs to be enhanced if a language barrier is present. Thus, when vaccine testing is carried out, research companies and organisations need to take into consideration the language, religion and cultural practices in that particular demographic, if not taken into consideration this could potentially create a ethical dilemma. If the testing and research harms or affects the customs and practices of a demographic group this would create a human rights issue. The success of a vaccine is dependent on the trial target population. These trials are meant to test the efficacy of a vaccine in different populations. Would one consider it ethical to forgo these trials in vulnerable populations, such as those with a high percentage of children. Since they have weaker or less developed immune systems, this raises some ethical concerns. Companies, research groups, and volunteers need to take into account who the vaccine is being tested on or administered to. A sense of balance needs to be achieved to protect vulnerable populations and ensure their safety.
Disparities in access: The distribution and storage of the consequent SARS-CoV-2 vaccination pose serious difficulties as the logistics create large disparities for access to the vaccination across several regions across the globe. Thus, according to Pfizer, a leading biopharmaceutical company in SARS-CoV-2 vaccination development, recommends that their vaccination should be stored at conditions of “-70℃±10℃ for up to 10 days unopened.” (Pfizer 2020). Such physical conditions create hurdles when transporting this vaccination outside of The United States, being the country of origin. The ethics dilemma is certain individuals will have better access to the vaccination, due to technological innovation in that area which allows increased availability. It may be that certain communities and governments cannot afford to vaccinate the general population and have difficulties storing and transporting the vaccine. Should these communities be taken into consideration, how can world leaders ensure that even those that are disadvantaged receive the vaccine despite geographic distance?
Mandates: Some individuals are against mandating vaccinations on the grounds of religious or philosophical objections. In the United States for example, in an effort to protect the largest number of individuals, some public health vaccines may have regulations which transgress an individual’s right to autonomy. When individuals attempt to exercise their right to refuse vaccination for themselves or their children, in their mind protecting themselves as they do not agree or accept the scientific evidence about vaccine safety and efficacy, tensions may arise.
Importance of herd immunity
“...if immunity is unevenly distributed within a population, clusters of susceptible hosts that frequently contact one another may remain. Even if the proportion of immunized individuals in the population as a whole surpasses the herd immunity threshold, these pockets of susceptible individuals are still at risk for local outbreaks.” - Haley E. Randolph and Luis B. Barreiro. CellPress, Herd Immunity: Understanding COVID-19
If the herd immunity threshold value for a certain population is high, more people need to be immune to the virus to protect those who are not. This is the reason that the proper use and development of vaccine programmes is crucial. Countries need to make long-lasting impacts when planning on making a large portion of their population immune to SARS-CoV-2, either through directly vaccinating viable candidates, or by younger or immunocompromised persons indirectly being protected by immune individuals. Vaccination programmes and plans are currently in effect, and the manufacturing, shipping, and distribution of vaccines are being managed by new task forces formed for the sole purposes of these vaccination efforts.
COVAX, an organisation founded by the WHO, the government of France, and the European Commission, has higher-income and lower-income economies who have joined the initiative and pooled together the necessary resources for vaccine development. Thus, bringing governments and manufacturers together to ensure that eventually vaccines for COVID-19 will reach those who are greatest in need of them, regardless of their geographical location or socioeconomic status.
Schematic depiction of the disease propagation dynamics when one infected individual is introduced into a completely susceptible population (top panel) versus a situation in which an infected individual is introduced into a population that has reached herd immunity threshold (bottom panel). In the naive population, an outbreak quickly emerges, whereas under the scenario of herd immunity, the virus fails to spread and persist in population. Source: ScienceDirect
Methods in combating viral effects and COVID-19 symptoms
Other than resorting to vaccination, other methods of treatments were utilised as the vaccine had not been initially established. One method used by healthcare professionals was the use of convalescent plasma treatment. The use of this treatment mimics acquired immunity as the patient is introduced to antibodies extracted from those who have overcome the SARS-CoV-2 virus, this method of treatment seems to be highly effective in reducing mortality. An article published from The Lancet, Infectious Diseases, claims that patients who suffered with severe COVID-19 symptoms and were treated with the convalescent plasma saw significant reduction in the SARS-Cov-2 viral loads. Although effective, the convalescent plasma treatment has some difficulties, in order to get plasma rich with antibodies, individuals who have overcome the virus need to donate their plasma extracted from blood, which contains the antibodies used to combat the virus. Additionally, efficacy of convalescent plasma treatment is mostly evident when utilised during the initial infection stage of COVID-19.
A second treatment option utilised to to improve immune response in COVID-19 patients is the use of a cocktail antibody treatment, REGN-COV2, the treatment has the ability to reduce viral load as the monoclonal antibodies against SARS-CoV-2 neutralise viral particles.
The antibody cocktail therapy, initially introduced by the biotechnology company, Regeneron. According to trials done by the company, the treatment was highly beneficial to COVID-19 patients whose immune response had not yet been initiated once the virus entered the patient's body. On 9 January 2021, in a personal interview Dr. A. Shah. confirmed the most prominent advantage appeared to be how the treatment had abilities to alleviate symptoms of COVID-19. Although effective, this treatment is not a direct cure for the disease and thus other methods of prevention and cure must be investigated.
An effective therapeutic drug used to reduce viral load of SARS-CoV-2 is the antiviral drug remdesivir, administered intravenously to hospitalised patients suffering severe COVID-19 symptoms. When tested with in vitro studies, the drug has the ability to inhibit the RNA-dependent RNA-polymerase of the SARS-CoV-2. According to a paper published by The New England Journal of Medicine, found through a study that patients who had been treated with remdesivir saw shorter recovery time than those not treated with the drug. Although the drug was initially tested in vitro and showed significant results in reducing viral load, this drug still needs more scientific testing and analysis. The advantage of reducing infection recovery time with the drug does not eliminate the effects and symptoms of the virus but rather alleviates the time to recover.
Vaccines are the world’s best effort in combating the current pandemic. Although confidence and trust have already been established in vaccine technologies, nuanced ethical discussions must still be considered. The COVID-19 pandemic has shown that through cooperation and humanity’s drive to solve a common goal, incredible and unprecedented events can take place. By the end of 2021, billions of vaccine doses will be administered, bringing us closer to having this pandemic under control. With these prevention methods considered, the use of other widely studied and researched methods such as convalescent plasma treatment, monoclonal antibody treatment and remdesivir are effective methods to combat the effects of SARS-CoV-2 in situations where a vaccination is not present.
Although for many a vaccine being a solution to the current pandemic, the idea can be daunting for others, due to misinformation and biased opinions. The manner which the vaccine is tested, distributed and mandated could all potentially create an ethical dilemma.
About the Authors
Coronavirus Disease (COVID-19) - events as they happen (2020). Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
Randolph, H. and Barreiro, L. (2020) "Herd Immunity: Understanding COVID-19", Immunity, 52(5), pp. 737-741. doi: 10.1016/j.immuni.2020.04.012.
COVID-19 (coronavirus disease 2019) January 2020 updates | MIT Medical (2020). Available at: https://medical.mit.edu/COVID-19/jan2020-updates
Neerukonda, S. and Katneni, U. (2020) "A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions", Pathogens, 9(6), p. 426. doi: 10.3390/pathogens9060426.
National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases, 2020, “Frequently Asked Questions”, https://www.cdc.gov/coronavirus/2019-ncov/faq.html#Spread,
Centers for Disease Control and Prevention. 2020. COVID-19 ACIP Vaccine Recommendations. [ONLINE] Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html. [Accessed 8 January 2021]
Ethical Issues and Vaccines | History of Vaccines (2010). Available at: https://www.historyofvaccines.org/index.php/content/articles/ethical-issues-and-vaccines
Chen, L., Xiong, J., Bao, L. and Shi, Y., 2020. 'Convalescent plasma as a potential therapy for COVID-19', The Lancet, vol. 20, no. 4, pp. 398-400.
John H. Beigel, et al.,. 2020. ‘Remdesivir for the Treatment of Covid -19 - Final Report’, The New England Journal of Medicine, 383:1813-1826. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2007764
Vaccinating Boys and Girls Against HPV (2020). Available at: https://www.cdc.gov/hpv/parents/vaccine
Pfizer. 2020. COVID-19 Vaccine U.S. Distribution Fact Sheet. [ONLINE] Available at:https://www.pfizer.com/news/hot-topics/covid_19_vaccine_u_s_distribution_fact_sheet.
Wikipedia. 2020. “Medical experimentation in Africa.” [ONLINE] Available https://en.wikipedia.org/wiki/Medical_experimentation_in_Africa#Sterilisation_experiments_in_German_South-West_Africa_(now_part_of_Namibia):_Late_1800s%E2%80%931910s.
Neerukonda, S. and Katneni, U. (2020) "A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions", Pathogens, 9(6), p. 426. Doi: 10.3390/pathogens9060426.
Boost for global response to COVID-19 as economies worldwide formally sign up to COVAX facility (2020). Available at: https://www.who.int/news/item/21-09-2020-boost-for-global-response-to-covid-19-as-economies-worldwide-formally-sign-up-to-covax-facility#:~:text=64%20higher%20income%20economies%20have,and%20wherever%20they%20live.
Convalescent plasma therapy for COVID-19 is safe. | Immunopaedia (2020). Available at: https://www.immunopaedia.org.za/breaking-news/convalescent-plasma-therapy-for-covid-19-is-safe/
Regeneron Pharmaceuticals, Inc. (2020) “Regeneron's REGN-COV2 antibody cocktail reduced viral levels and improved symptoms in non-hospitalized COVID-19 patients,” Available at: https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and
Krosin, Michael T et al. “Problems in comprehension of informed consent in rural and peri-urban Mali, West Africa.” Clinical trials (London, England) vol. 3,3 (2006): 306-13. doi:10.1191/1740774506cn150oa