9/9/2021 8:11:50 PM
To be or not to be vaccinated against COVID19? A challenging issue
This is how the Immunology Team starts the debate!
Since the first days of the COVID-19 pandemic, the world has struggled to answer this question: How could we end this misery? It did not take us long to find out that we were not ready for a pandemic. According to the latest statistics, as of 9th September 2021, there have been more than 219 million confirmed cases of COVID-19, including more than 4.61 million deaths. Therefore, science-based measures are necessary to prevent this epidemic and its subsequent outcomes.
Based on our experiences with previous epidemics, we knew that we had to take a multi-layer approach featuring vaccines, public health measures, international cooperation with more depth and breadth, prophylactics to control the disease, and we knew the most important tool by far is vaccines.
In the last two centuries, control of epidemics like smallpox and the complete eradication of the disease has been achieved successfully, thanks to vaccines (1).
Previously, the fastest vaccine that went from development to deployment was the Mumps vaccine in the 1960s that took about four years. It even took us 28 years to develop and approve an effective vaccine against chickenpox (2). As soon as we understood that the spread of the SARS-COV2 virus was a public health emergency of international concern, all hands were put on the neck (3). In 2020, vaccines for covid-19 had shattered previous records; to put it in perspective, the development of the Moderna vaccine took 69 days. The recombinant genetic technology and billions of dollars poured into research, global unity, and efforts made it possible to develop, test, and approve these vaccines at an unprecedented pace.
The scientific communities worldwide started the production of the COVID-19 vaccines in 2020. Although existing technologies helped us produce effective vaccines against SARS-COV-2, many challenges and probable questions are still impossible to answer quickly. Accelerated approaches for the development of COVID-19 vaccines have considerably reduced mortality and hospitalization rate. However, unlike approved vaccines, they have not gone through the main stages, and the durability of immune responses following vaccination has not been thoroughly addressed. In addition, the new SARS-CoV-2 variants pose many challenges to vaccine efficacy, leading to a reduction in vaccine efficacy from alpha to delta and other probable emerging variants. Despite the initial high efficacy of Pfizer ( 95 to 99%) and AstraZeneca vaccines (75 to 99 %), a result of a new study showed the DELTA variant (B.1.617.2) is six-fold less sensitive to serum neutralizing antibodies from recovered individuals and eight-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G (4).
Furthermore, recent evidence indicated that natural infection might provide better protection against SARS-CoV-2 than vaccination (5). A new survey from Israel showed immunity gained after recovering from COVID-19 is more protective against the Delta variant than vaccine-induced immunity. They acknowledged that natural immunity was estimated to provide 13 times better protection against infection, symptomatic disease, and hospitalization than having two doses of the Pfizer-BioNTech vaccine (6). Potential side effects are indeed among the drawback of worldwide COVID-19 vaccination. For instance, some COVID-19 vaccines particularly, vector-based vaccines like AstraZeneca, could lead to thrombosis and cardiovascular implications, especially in women under 50 years old (7).
Despite these concerns, WHO recommends getting COVID-19 vaccines even if people have already been exposed to the infection. Based on the results published so far, vaccination against COVID-19 has shown high effectiveness against the disease by inducing protective immune responses. Evidence from several sets of scientific reports indicates that vaccination against COVID-19 has been very effective at preventing severe illness, hospitalization, ICU admission, and death against alpha and also new variants of concern (8, 9). An accumulating body of evidence indicates that people fully vaccinated against SARS-COV2 are less likely to have symptomatic or asymptomatic infections or transmit the virus to others (10).
Although one of the main drivers of vaccine hesitancy has been a lack of information regarding the vaccine's potential side effects, recent reports reinforce the safety of these vaccines. In the largest real-world study involving 2.4 million people vaccinated with Pfizer vaccine, short-term and medium-term adverse events between vaccinated and unvaccinated persons and separately between unvaccinated persons infected and not infected with coronavirus were compared. The results suggested that the vaccine is safe, while COVID-19 infection is associated with numerous serious adverse events. Four of 25 studied side effects were associated with the vaccine, including myocarditis, lymphadenopathy, appendicitis, and herpes zoster infection. While myocarditis was the most severe one, with more than 2.7 cases per 100,000 vaccinated persons, SARS-CoV-2 infection in unvaccinated individuals was associated with an excess of 11 cases per 100,000 infected persons. COVID-19 infection was also associated with a significantly increased risk of pericarditis, arrhythmias, heart attacks, strokes, pulmonary embolism, deep-vein thrombosis, and acute kidney damage (11). This careful epidemiological study provides reliable information on vaccine safety. Those who have hesitated vaccination due to concerns about rare side effects (e.g., myocarditis) should be informed that the risks for this side effect are higher among unvaccinated infected individuals.
Notably, the severe symptoms and mortality mainly increase in adults and patients with co-morbidities like diabetes and obesity following infection. According to the results of clinical studies, COVID-19 vaccination showed similar efficacy and safety in individuals with co-morbidities and those without any underlying medical conditions. Regarding the fact that individuals with co-morbidities have a higher risk of progression to severe conditions or death when infected with COVID-19, the benefits of the COVID-19 vaccination outweigh the risks(12). Pregnant women may experience more severe disease compared to non-pregnant control due to the deviation of cytokine profile toward TH2 immunity. Vaccination helps this group to have an effective immune response against SARS-COV-2 and create neutralizing antibodies able to pass the placenta(13).
Another important aspect that should be considered is the potential beneficial effect of vaccination against the generation of new variants of SARS-COV-2. Viruses experience a random set of mutations during replication. Mutation rate drives the evolution of new variants and genome variability, thereby enabling viruses to escape host immune responses. The high the replication rate of the virus is, the more likely new variants are generated (14, 15). By inducing a protective immune response, vaccination could effectively control virus replication and reduce the likelihood of new variants' emergence.
It should also be noted that elderly people, due to senescence of the immune system, do not usually mount a strong protective immune response against SARS-COV-2 (16). By enhancing immune responses, vaccination considerably reduces vulnerability to severe disease in elderly people, the age in which infection is associated with a higher rate of severe illness and mortality (17).
COVID-19 has also been associated with a global economic and social crisis. According to the International Labor Organization (ILO), 25 million jobs could be lost worldwide due to the COVID-19 pandemic. Vaccination could be viewed as an immediate, mid-and long-term recovery effort needed to combat the social and economic consequences of COVID-19.
Moreover, SARS-COV (Severe Acute Respiratory Syndrome Coronavirus) and the MERS-COV (the Middle East Respiratory Syndrome Coronavirus) were detected in 2002 and 2012, respectively, and the recent outbreak of SARS-CoV-2 indicates that coronavirus-related diseases can be a permanent threat for humans. In this regard, vaccination could be viewed as an indispensable tool to control coronavirus disease.
In addition, the reproductive number of new SARS-COV-2 variants like delta variant (R0= 3.2-8 mean: 5.8) is much higher than the R0 of the ancestral strain with a R0 of 2.79. This nature is correlated with the virus's higher transmissibility, leading to a higher incidence of the disease in societies (18). Under selective pressure, evolution always forces the generation of new viral variants with higher R0 making higher vaccine coverage indispensable.
Till the day of this paper's submission, as of 9th September, 5.57 billion doses of COVID-19 vaccine have been given, and 2.29 billion people (29.4% of the world's population) have been fully vaccinated (according to ourworldindata.org). Unlike smallpox, the SARS-COV-2 virus has features that make it impossible to eradicate: it has animal vectors and can fully spread from an infected person during the asymptomatic (incubation) period. Nonetheless, vaccination can significantly prevent severe disease and mortality. So the solution is "Vaccinate and Manage," as we have done with other contagious infectious diseases like Polio, Hepatitis B, measles, and mumps.
Today vaccines are not perfect, but all of them do the job we initially wanted them to do: prevent severe symptoms, reduce hospitalization, mitigate virus replication, and thus the probability of newer, more dangerous variant's appearance and slowing down the transmission.
We cannot compare vaccines by their efficacy rate because each vaccine's clinical trial has been done at a different time, place, population, and under different conditions. Thus the best vaccine for you is the one available for you. So do not hesitate, get informed from reliable sources, get your vaccine shot (if you do not have medical contraindications), and respect the public safety measures even if you are fully vaccinated.
Nonetheless, the COVID-19 vaccines should be continuously monitored for safety issues, as we have done with other medications. We need to understand the overall safety and the overall benefits and then have robust systems to detect uncommon side effects and put them in context with overall risk-benefit to individuals and communities. Right now, as far as we know, for the vast majority of people, the risk of the disease vastly outweighs the risk of the vaccine's adverse effects.
1. Barquet N, Domingo P. Smallpox: the triumph over the most terrible of the ministers of death. Annals of internal medicine. 1997;127(8_Part_1):635-42.
2. Plotkin SL, Plotkin SA. A short history of vaccination. Vaccines. 2004;5:1-16.
3. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506.
4. Mlcochova P, Kemp S, Dhar MS, Papa G, Meng B, Mishra S, et al. SARS-CoV-2 B. 1.617. 2 Delta variant emergence, replication and sensitivity to neutralizing antibodies. Microbiology. 2021.
5. Krammer F. Correlates of protection from SARS-CoV-2 infection. The Lancet. 2021;397(10283):1421-3.
6. Gazit S, Shlezinger R, Perez G, Lotan R, Peretz A, Ben-Tov A, et al. Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections. medRxiv. 2021.
7. Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, et al. Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. bmj. 2021;374.
8. Jara A, Undurraga EA, González C, Paredes F, Fontecilla T, Jara G, et al. Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. New England Journal of Medicine. 2021.
9. Moghadas SM, Vilches TN, Zhang K, Wells CR, Shoukat A, Singer BH, et al. The impact of vaccination on COVID-19 outbreaks in the United States. medRxiv. 2021.
10. Harder T, Koch J, Vygen-Bonnet S, Külper-Schiek W, Pilic A, Reda S, et al. Efficacy and effectiveness of COVID-19 vaccines against SARS-CoV-2 infection: interim results of a living systematic review, 1st January to 14th May 2021. Eurosurveillance. 2021;26(28):2100563.
11. Bernal JL, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test-negative case-control study. bmj. 2021;373.
12. Choi WS, Cheong HJ. COVID-19 Vaccination for People with Co-morbidities. Infection & Chemotherapy. 2021;53(1):155.
13. Beigi RH, Krubiner C, Jamieson DJ, Lyerly AD, Hughes B, Riley L, et al. The need for inclusion of pregnant women in COVID-19 vaccine trials. Vaccine. 2021;39(6):868.
14. Kimura I, Kosugi Y, Wu J, Yamasoba D, Butlertanaka EP, Tanaka YL, et al. SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance. bioRxiv. 2021.
15. Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon KH, et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2020;370(6523):1464-8.
16. Jordan RE, Adab P, Cheng K. Covid-19: risk factors for severe disease and death. British Medical Journal Publishing Group; 2020.
17. Hasseli R, Mueller-Ladner U, Hoyer BF, Krause A, Lorenz H-M, Pfeil A, et al. Older age, co-morbidity, glucocorticoid use, and disease activity are risk factors for COVID-19 hospitalization in patients with inflammatory rheumatic and musculoskeletal diseases. Rmd Open. 2021;7(1):e001464.
18. Liu Y, Rocklöv J. The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus. Journal of Travel Medicine. 2021.