A response to a friend who insisted:
1. All early COVID-19 vaccines were mRNA based
2. COVID-19 vaccines did not help, and killed or harmed millions
Some initial observations: Nothing on social media, including this, should be taken as evidence. Social media posts can be a useful starting point for investigation, as I hope this will be, but should always be questioned – Is that true? Was it true when it was said? What is the evidence for that? How credible is that evidence? How credible are the people promulgating a particular point of view? Do conclusions rely on conspiracy theories, or a belief in widespread corruption, or that “they” are censoring data? Have there been more recent or larger studies with different results? How well does the evidence support the conclusions? Were studies well-designed? Is any statistical analysis appropriate and accurate? Are basic scientific facts accurate?
Answering such questions may not always be easy. In the case of anything involving health and COVID-19, for example, even the most basic understanding rests on even more basic scientific knowledge, at least first year chemistry, physics, biology, and statistics, and a semester of immunology. Those fundamentals begin to tell you what questions to ask, enable you to identify basic errors in fact, and give you some idea how to find well-founded information. I don’t have the immunology, by the way, so you should not take anything I say on the subject for granted!
It is always OK to ask questions. But if we are not experts in a field, questioning should always be done with a measure of humility, and be a genuine search for knowledge, not silly smart-arsy or “gotcha” pretend questions, which just make the asker look foolish and insincere.
Now onward and upward! References listed in-line, and compiled below. If you are not used to reading scientific papers you may find this heavy going. That’s OK. Take it in stages. Ask questions along the way. Look at the references. Press on regardless! And let us all give thanks for the knowledge and persistence and attention to detail of medical researchers, and the effectiveness of modern pharmaceuticals, which have resulted in humans now living longer and healthier lives than at any time in our history.
Not all early COVID-19 vaccines used mRNA technology. The Pfizer-BioNTech and Moderna COVID-19 vaccines used mRNA technology. The vaccines developed by AstraZeneca, Johnson & Johnson, and those produced in China, such as Sinovac and Sinopharm, did not. Instead, these vaccines used different approaches, such as using a harmless cold virus (adenovirus) to deliver genetic material into cells, or using an inactivated version of the SARS-CoV-2 virus.
The most widely used COVID-19 vaccines globally have been the Pfizer-BioNTech vaccine, known as BNT162b2, and the Moderna vaccine, known as mRNA-1273, both of which are mRNA vaccines. These vaccines have been administered extensively across various countries due to their high efficacy rates and the rapid development and approval processes that characterized their introduction during the pandemic. Studies have reported that the efficacy of BNT162b2 against symptomatic COVID-19 infection is approximately 91.3% (Gálvez, 2023), while the efficacy of mRNA-1273 is reported to be around 93.2% (Gálvez, 2023). Both vaccines utilize messenger RNA technology to prompt an immune response, distinguishing them from traditional vaccine types such as viral vector or inactivated virus vaccines.
The widespread acceptance and deployment of mRNA vaccines like Pfizer-BioNTech and Moderna is not a result of any nefarious conspiracy, but of the fact that their delivery system allows for a quicker response to emerging pathogens. The mRNA vaccines work by using a small piece of the virus’s genetic material to instruct cells to produce a protein that is part of the virus, thereby eliciting an immune response without causing the disease itself (Soegiarto et al., 2022). Their quick response time and high effectiveness, coupled with low cost, have been pivotal in global vaccination efforts against COVID-19, leading to high vaccination rates in many populations.
A brief discursion into spike proteins. The spike protein of coronaviruses, including SARS-CoV-2, plays a crucial role in the viral life cycle by mediating the virus’s entry into host cells. This glycoprotein is essential for the virus’s ability to infect cells, as it facilitates binding to specific receptors on the host cell surface, such as angiotensin-converting enzyme 2 (ACE2) (Shang et al., 2020). The interaction between the spike protein and ACE2 is a critical determinant of viral infectivity and pathogenicity, as alterations in the spike protein can influence the virus’s ability to evade the host immune response and enhance its transmissibility (Zhou, 2021; Ding et al., 2021). This makes targeting the virus’s spike protein a key element of reducing infection and transmission.
These immunogenic properties make the spike protein a primary target for vaccine development. Vaccines that elicit an immune response against spike proteins in COVID-19and other coronaviruses have been shown to produce high-titer neutralising antibodies, which are essential for preventing infection (Baisa et al., 2020; Guo et al., 2015). For instance, studies have demonstrated that recombinant spike proteins can effectively stimulate robust immune responses in animal models, leading to the production of antibodies that neutralise the virus (Wal et al., 2022; Guo et al., 2015). This has led to the design of various vaccine platforms, including mRNA and viral vector vaccines, which aim to induce a strong immune response against the spike protein (Shen et al., 2021).
The Sinovac COVID-19 vaccine, known as CoronaVac, has been widely used in various countries, particularly in Asia and Latin America. It is an inactivated virus vaccine. That is, it is not an mRNA vaccine. It has been administered extensively in countries such as Brazil, Chile, Indonesia, and Turkey, among others (Uzun et al., 2022). The World Health Organization (WHO) has included Sinovac in its Emergency Use Listing, which has facilitated its widespread distribution and use, particularly in regions with limited access to mRNA vaccines.
A study in Brazil reported that the efficacy of a single dose of CoronaVac was approximately 50.7% against symptomatic COVID-19, while two doses yielded an efficacy of about 67% (Li et al., 2021). Furthermore, research has indicated that while the vaccine is effective in reducing severe disease and hospitalization, its effectiveness against variants such as Delta has been a subject of ongoing investigation (Li et al., 2021). In Turkey, a significant decrease in healthcare worker deaths was observed following the vaccination campaign with Sinovac, underscoring its role in mitigating severe outcomes (Uzun et al., 2022).
Despite its widespread use, the Sinovac vaccine has faced scrutiny regarding its immunogenicity compared to mRNA vaccines. Studies have shown that individuals vaccinated with Sinovac may have lower levels of neutralizing antibodies compared to those vaccinated with mRNA vaccines like Pfizer-BioNTech (Ata et al., 2022). This has raised discussions about the potential need for booster doses, particularly in populations with compromised immune responses, such as cancer patients.
In terms of safety, Sinovac has been reported to have a favourable safety profile, with most adverse reactions being mild and similar to those observed with other inactivated vaccines. Common side effects include injection site pain and mild fever, although the incidence of fever appears to be lower compared to mRNA vaccines (Ata, 2023). Observational studies have also indicated that the vaccine is generally well-tolerated among different demographic groups, including those with comorbidities (Zachreini et al., 2022).
Studies have shown that like inactivated virus vaccines, adenovirus vector vaccines like AstraZeneca have a lower efficacy compared to mRNA vaccines such as Pfizer-BioNTech and Moderna. The AstraZeneca vaccine has been reported to have an efficacy of approximately 76% against symptomatic COVID-19 after two doses (Toubasi et al., 2022). In contrast, mRNA vaccines have demonstrated significantly higher efficacy rates, with Pfizer-BioNTech showing around 94% efficacy and Moderna around 95% against symptomatic infection (Mahallawi & Mumena, 2021). This disparity in efficacy can be attributed to the different mechanisms of action and immune responses elicited by the two types of vaccines.
Many further studies confirm mRNA vaccines have superior efficacy compared to non-mRNA vaccines like AstraZeneca (Dagan et al., 2021). mRNA vaccines have shown higher effectiveness in preventing severe disease and hospitalization, particularly against variants of concern such as Delta and Omicron, and even amongst patients with significant co-morbidities (Drácz et al., 2022; Bidari et al., 2022). For instance, a nationwide study in Israel reported that the mRNA vaccine was 92% effective in preventing severe disease, compared to lower rates for viral vector vaccines (Dagan et al., 2021).
What about in Australia? The first COVID-19 vaccines used in Australia were the Pfizer-BioNTech vaccine (BNT162b2), an mRNA vaccine, and the AstraZeneca vaccine (ChAdOx1-S), which used an adenovirus delivery method. The Pfizer-BioNTech vaccine was granted provisional approval by the Therapeutic Goods Administration (TGA) in January 2021, followed by the AstraZeneca vaccine in February 2021 (Dagan et al., 2021). Both vaccines were pivotal in Australia’s initial vaccination rollout, with the Pfizer vaccine being primarily used for younger populations and vulnerable groups, while AstraZeneca was recommended for older adults and those unable to access mRNA vaccines (Varma et al., 2022).
Real-world data from Australia indicated that mRNA vaccines provided better protection against COVID-19-related hospitalization and death compared to AstraZeneca, especially in younger populations who were more likely to receive the mRNA vaccines (Varma et al., 2022; John et al., 2022). This trend has been consistent across various studies, reinforcing the notion that mRNA vaccines are more effective in controlling the spread of COVID-19 and reducing severe outcomes compared to their non-mRNA counterparts (Drácz et al., 2022; Bidari et al., 2022).
Despite what you may have read on Facebook or heard in YouTube videos, evidence consistently confirms that vaccination against COVID-19 is associated with lower all-cause mortality rates compared to unvaccinated individuals.
A cross-sectional study conducted across 178 countries demonstrated that higher vaccination coverage correlates with lower all-cause mortality rates, suggesting that immunization efforts have played a crucial role in mitigating the pandemic’s impact (Mendoza-Cano, 2023). This finding is supported by data from the U.S., where a report indicated that unvaccinated individuals experienced substantially higher rates of COVID-19 cases, hospitalizations, and deaths compared to those who were fully vaccinated (Scobie et al., 2021). Furthermore, a study in Brazil highlighted that vaccination had a significant indirect impact on mortality trends, reinforcing the strong scientific consensus that increased vaccination coverage leads to decreased mortality rates (Percio et al., 2021).
In addition to overall mortality, specific studies have examined the clinical outcomes of vaccinated versus unvaccinated patients. For instance, a study from India found that vaccinated patients exhibited lower severity of COVID-19 pneumonia, which translated into reduced rates of mechanical ventilation and death compared to their unvaccinated counterparts (Bajpai et al., 2022). Similarly, research conducted in the U.S. indicated that vaccinated individuals hospitalized with COVID-19 had lower odds of requiring intensive care and had a significantly reduced likelihood of death (Sagiraju et al., 2021). These findings underscore the protective effect of vaccination not only against COVID-19 itself but also against severe outcomes that could lead to increased mortality.
A comprehensive observational study in the U.S. reported that counties with high vaccination rates observed more than an 80% reduction in mortality compared to areas with low vaccination coverage (Suthar et al., 2022). This stark contrast emphasizes the critical role of vaccination in enhancing population immunity and reducing the burden of COVID-19-related deaths.
While some social media posts raise concerns about mortality related to vaccination, the overwhelming evidence based on real-world research demonstrates clearly that vaccination significantly reduces the risk of severe illness and death from COVID-19 (Lytras et al., 2022). For example, a large systematic review highlighted that vaccination is associated with lower infection fatality rates, which is crucial in understanding the overall impact of vaccination on public health (Meyerowitz-Katz & Merone, 2020).
The evidence strongly supports the conclusion that individuals vaccinated against COVID-19 experience significantly lower all-cause death rates compared to those who are unvaccinated.
In the United States, for example, the proportion of COVID-19 deaths among vaccinated and unvaccinated individuals has been a significant area of research, particularly as vaccination efforts have ramped up. Studies consistently show that unvaccinated individuals account for a substantial majority of COVID-19-related deaths. For instance, a study by Samuels et al. indicates that unvaccinated individuals were 10 times more likely to be hospitalized and 11 times more likely to die from COVID-19 compared to those who were fully vaccinated (Samuels et al., 2022). Similarly, research by Balian et al. highlights that unvaccinated patients had a significantly higher likelihood of requiring intensive care and experiencing fatal outcomes, with an adjusted odds ratio of 0.33 for vaccinated patients progressing to mechanical ventilation or death (Balian et al., 2023).
Further supporting this trend, Yavuz and Sezerol found that approximately 77% of COVID-19 deaths in their study population were among unvaccinated or incompletely vaccinated individuals (Yavuz & Sezerol, 2023), despite the unvaccinated being a much smaller proportion of the population. This aligns with findings from Havers et al., which reported that a significant proportion of hospitalized patients were unvaccinated, particularly in older age groups where vaccination coverage was high (Havers et al., 2022). The data from multiple large studies confirms that while vaccinated individuals, particularly those with serious co-morbidities, may still contract severe cases of COVID-19, the mortality rate among vaccinated patients is markedly lower.
References
Ata, S., Çil, T., Duman, B. B., & Ünal, N. (2022). Evaluation of antibody response after two doses of the sinovac vaccine and the potential need for booster doses in cancer patients. Journal of Medical Virology, 94(6), 2487-2492. https://doi.org/10.1002/jmv.27665
Baisa, G., Rancour, D. M., Mansfield, K. G., Burns, M., Martin, L., Cunha, D., … & Luke, K. (2020). A recombinant protein sars-cov-2 candidate vaccine elicits high-titer neutralizing antibodies in macaques… https://doi.org/10.1101/2020.12.20.422693
Balian, S., Bailey, B. A., Abboud, S., Kim, Y., Humphries, D., Kambali, S., … & Haddad, N. (2023). Comparative admission rates and infection severity of covid-19 among unvaccinated and vaccinated patients. Journal of Investigative Medicine, 71(4), 329-338. https://doi.org/10.1177/10815589221149191
Bidari, A., Asgarian, S., Mohammad, A. P., Naderi, D., Anaraki, S. R., Mesgarha, M. G., … & Naderkhani, M. (2022). Immune thrombocytopenic purpura secondary to covid‐19 vaccination: a systematic review. European Journal of Haematology, 110(4), 335-353. https://doi.org/10.1111/ejh.13917
Dagan, N., Barda, N., Kepten, E., Miron, O., Perchik, S., Katz, M. A., … & Balicer, R. D. (2021). Bnt162b2 mrna covid-19 vaccine in a nationwide mass vaccination setting. New England Journal of Medicine, 384(15), 1412-1423. https://doi.org/10.1056/nejmoa2101765
Ding, C., He, J., Zhang, X., Jiang, C., Sun, Y., Zhang, Y., … & Gao, Y. (2021). Crucial mutations of spike protein on sars-cov-2 evolved to variant strains escaping neutralization of convalescent plasmas and rbd-specific monoclonal antibodies. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.693775
Drácz, B., Müller, V., Takács, I., Hagymási, K., Dinya, E., Miheller, P., … & Werling, K. (2022). Effectiveness of covid-19 vaccination with mrna vaccines for patients with cirrhosis in hungary: multicentre matched cohort study. Vaccines, 11(1), 50. https://doi.org/10.3390/vaccines11010050
Gálvez, J.M.; Pinzón-Rondón, Á.M.; Chaparro-Solano, H.M.; Tovar-Romero, H.V.; Ramírez-Prieto, J.; Ortigoza-Espitia, S.A.; Ruiz-Sternberg, Á.M. (2023) Effectiveness of the Booster Dose in Protecting against COVID-19, Vaccines 2023, 11, 1461. https://doi.org/10.3390/vaccines11091461
Guo, X., Deng, Y., Chen, H., Lan, J., Wang, W., Zou, X., … & Tan, W. (2015). Systemic and mucosal immunity in mice elicited by a single immunization with human adenovirus type 5 or 41 vector‐based vaccines carrying the spike protein of middle east respiratory syndrome coronavirus. Immunology, 145(4), 476-484. https://doi.org/10.1111/imm.12462
Havers, F., Pham, H., Taylor, C. A., Whitaker, M., Patel, K., Anglin, O., … & McMorrow, M. (2022). Covid-19-associated hospitalizations among vaccinated and unvaccinated adults 18 years or older in 13 us states, january 2021 to april 2022. JAMA Internal Medicine, 182(10), 1071. https://doi.org/10.1001/jamainternmed.2022.4299
Li, X., Huang, Y., Wang, W., Jing, Q., Zhang, C., Qin, P., … & Zhong, N. (2021). Effectiveness of inactivated sars-cov-2 vaccines against the delta variant infection in guangzhou: a test-negative case–control real-world study. Emerging Microbes &Amp; Infections, 10(1), 1751-1759. https://doi.org/10.1080/22221751.2021.1969291
Lytras, T., Athanasiadou, M., Demetriou, A., Stylianou, D., Heraclides, A., & Kalakouta, O. (2022). Excess mortality in cyprus during the covid-19 pandemic and its lack of association with vaccination rates.. https://doi.org/10.1101/2022.08.05.22278487
Mahallawi, W. H. and Mumena, W. A. (2021). Reactogenicity and immunogenicity of the pfizer and astrazeneca covid-19 vaccines. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.794642
Mendoza-Cano, O., Trujillo, X., Huerta, M., Ríos-Silva, M., Guzmán-Esquivel, J., Lugo-Radillo, A., … & Murillo-Zamora, E. (2023). Assessing the influence of covid-19 vaccination coverage on excess mortality across 178 countries: a cross-sectional study. Vaccines, 11(8), 1294. https://doi.org/10.3390/vaccines11081294
Meyerowitz-Katz, G. and Merone, L. (2020). A systematic review and meta-analysis of published research data on covid-19 infection fatality rates. International Journal of Infectious Diseases, 101, 138-148. https://doi.org/10.1016/j.ijid.2020.09.1464
Pércio, J., Cabral, C. M., Fantinato, F. F. S. T., Barrera, L. S. G., & Araújo, W. N. d. (2021). Indirect impact of covid-19 vaccination on weekly trends in morbidity and mortality indicators in brazil, 2020 to 2021.. https://doi.org/10.21203/rs.3.rs-1146790/v1
Riad, A., Pokorná, A., Mekhemar, M., Conrad, J., Klugarová, J., Koščík, M., … & Attia, S. (2021). Safety of chadox1 ncov-19 vaccine: independent evidence from two eu states. Vaccines, 9(6), 673. https://doi.org/10.3390/vaccines9060673
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., … & Li, F. (2020). Structural basis of receptor recognition by sars-cov-2. Nature, 581(7807), 221-224. https://doi.org/10.1038/s41586-020-2179-y
Sagiraju, H. K. R., Elavarasi, A., Gupta, N., Kumar, R., Paul, S. S., Vig, S., … & Bhatnagar, S. (2021). The effectiveness of sars-cov-2 vaccination in preventing severe illness and death – real-world data from a cohort of patients hospitalized with covid-19.. https://doi.org/10.1101/2021.08.26.21262705
Scobie, H. M., Johnson, A. G., Suthar, A. B., Severson, R., Alden, N., Balter, S., … & Silk, B. J. (2021). Monitoring incidence of covid-19 cases, hospitalizations, and deaths, by vaccination status — 13 u.s. jurisdictions, april 4–july 17, 2021. MMWR. Morbidity and Mortality Weekly Report, 70(37), 1284-1290. https://doi.org/10.15585/mmwr.mm7037e1
Soegiarto, G., Fajar, J. K., Wulandari, L., Anshory, M., Ilmawan, M., Asmiragani, A., … & Harapan, H. (2022). Seroconversion rates among different designs of covid-19 vaccines: a network meta-analysis of randomized controlled trials. F1000Research, 11, 299. https://doi.org/10.12688/f1000research.110281.1
Sagiraju, H. K. R., Elavarasi, A., Gupta, N., Kumar, R., Paul, S. S., Vig, S., … & Bhatnagar, S. (2021). The effectiveness of sars-cov-2 vaccination in preventing severe illness and death – real-world data from a cohort of patients hospitalized with covid-19.. https://doi.org/10.1101/2021.08.26.21262705
Samuels, S., Niu, J., Sareli, C., Sareli, A. E., & Eckardt, P. (2022). Characteristics, vaccination status and outcomes among healthy younger adults in a large public healthcare system in the south florida region. Journal of Community Health, 47(2), 371-377. https://doi.org/10.1007/s10900-022-01062-y
Shen, X., Tang, H., McDanal, C., Wagh, K., Fischer, W., Theiler, J., … & Montefiori, D. C. (2021). Sars-cov-2 variant b.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines.. https://doi.org/10.1101/2021.01.27.428516
Toubasi, A. A., Al-Sayegh, T., Obaid, Y. Y., Al-Harasis, S. M., & AlRyalat, S. A. (2022). Efficacy and safety of covid‐19 vaccines: a network meta‐analysis. Journal of Evidence-Based Medicine, 15(3), 245-262. https://doi.org/10.1111/jebm.12492
Uzun, O., Akpolat, T., Varol, A., Turan, S., Bektaş, Ş., Çetinkaya, P. D., … & İtil, O. (2022). Covid-19: vaccination vs. hospitalization. Infection, 50(3), 747-752. https://doi.org/10.1007/s15010-021-01751-1
Varma, S., Horton, A., Taylor, A., Ditchfield, M., Hope, S., & Rao, S. J. (2022). Myocarditis after covid ‐19 mrna vaccination in australia. Medical Journal of Australia, 217(5), 260-261. https://doi.org/10.5694/mja2.51657
Wal, P., Wal, A., Vig, H., Srivastava, A. K., & Kumar, A. (2022). The structure and mechanism of spike protein, as well as its role in numerous viral diseases. International Journal of Pharmaceutical Investigation, 12(2), 129-135. https://doi.org/10.5530/ijpi.2022.2.24
Yavuz, M. Y. and Sezerol, M. A. (2023). The vaccination characteristics and mortal causes analysis of covid-19 deaths at a district level. Journal of Medicine and Palliative Care, 4(2), 145-150. https://doi.org/10.47582/jompac.1255788
Zachreini, I., Bashiruddin, J., Tamin, S., Priyono, H., Mayangsari, I. D., Supartono, N., … & Manukbua, T. (2022). Covid-19 among indonesian ent specialist and resident after second dose of sinovac vaccination. F1000Research, 11, 1454. https://doi.org/10.12688/f1000research.126527.1
Zhou, I. Y. (2021). Link prediction of viral spike proteins and cell receptors using structural perturbation method.. https://doi.org/10.21203/rs.3.rs-1038054/v1