Covid-19 Vaccines May Be a Double Edged-Sword.
by Richard Cheng, M.D., Ph.D.
80% of people who contract Covid-19 develop only mild diseases. 20% of those who contract Covid-19 show no symptoms. The death rate of Covid-19 for young people up to 50 years of age is similar to an influenza. Between 50 and 70, it starts to increase (but still may not be much worse than a flu, unfortunately there is no age-specific breakdown data to compare with). At age above 75, the risk starts going up significantly.
While for most people, Covid-19 vaccine may not be necessary nor worthwhile, these vaccines may cause deleterious side effects. Antibody-Dependent Enhancement, described above, is just one of such concerns. Distrust of vaccines has been a long standing issue, which can’t be simply dismissed as anti-vaccine mentality1.
Covid-19 Vaccines: Light at the end of the very long tunnel?
The whole world has been immersed in the Covid-19 panic for the most part of 2020. Like US politics, the world also seems split towards Covid-19. Most people experience fear, anxiety and hopelessness, while a significant number of people seem to downplay the danger of Covid-19, not adhering the general warnings of facial masks and social distancing. Americans are not very patient people. After a couple of months of Covid fear and anxiety in the spring, we saw a decline of Covid statistics in the summer resulting in relaxed attitude towards Covid-19. But now, early winter, Covid stats seem to be creeping up again. We begin to see reports that some European countries and US states start locking down again. In the backdrop of unsettled US presidential election, I sense rising levels of fear, anxiety, anguish and even anger in the air. Some even fear the breakout of yet another civil war. This time of the year, winter blues and holiday depression will usually also begin to emerge. Just when the pieces for a perfect storm seem to be falling into places, Pfizer and Moderna both announced their “highly effective” vaccine.
What a shot in the arm: finally, the long-awaited savior has arrived.
After the initial excitement, some of us need to calm down and do a reality check. After some analysis with a dose of common sense, the picture down the road may not be as rosy as most of us want to believe, or at least not in the coming months.
Pfizer reported a Covid-19 vaccine effective in ~90% of 43,000 people. Moderna also reported their similar mRNA vaccine trial on ~30,000 people with 94% effectiveness. These reports really excited the world, offering a glimpse of light at the end of the long Covid-19 tunnel. These vaccines are mRNA vaccines, a new class of vaccines. In a nutshell, instead of injecting a piece of the virus (dead or alive) as in conventional vaccines, Pfizer’s and Moderna’s vaccines inject a messenger RNA to instruct the recipient’s body to start an immune reaction against the spike protein of the SARS-Cov2 virus. This spike protein is what this virus uses to infect and enter the host cell. If we can block this process, then we can block the infection or render it less harmful, at least. This is a brand-new vaccine strategy, one that has never been tested before. Questions towards both the effectiveness and safety arise. Some of the questions are pretty serious2.
- The mRNA vaccine technology is the first of its kind, longtime effectiveness and safety are unclear. Only time will tell. Pfizer says viral mutations are not a problem for their mRNA vaccine which will be effective against SARS-Cov2 viral mutants. This also remains to be seen.
- Among the younger population, Covid-19 is not more threatening than a seasonal flu. The population that Covid-19 causes more problems is primarily the eldest of the elderly and immune compromised. Will the vaccine protect the elderly, children, pregnant women and immune compromised? We don’t know the answer.
- Safety concerns. Several Covid-19 vaccine attempts have met with side effects severe enough to halt the clinical trial. Although Pfizer and Moderna didn’t report serious side effects of their vaccines so far among the 43,000+ and 30,000+ recipients. One of the concerns is a phenomenon called Antibody-Dependent Enhancement (ADE). More below on ADE.
- Other problems. To effectively halt the spread of Covid-19 worldwide, it’s estimated that ~2/3 of the world’s population need to develop immunity to Covid-19, whether through vaccine or viral exposure/infection. To immunize several billions of people worldwide or ~200 million in US is a daunting task, let alone that a large number of US residents are reported to be resistant to vaccines. CNN reports recently that up to 45% of people in a survey were against Covid-19 vaccines. Only about half of the people in the survey were willing to receive vaccines. To immunize half of the US population, it’ll still take a considerable amount of time to manufacture, distribute and immunize. We don’t know when that will happen, but we probably shouldn’t expect that before summer of 2021.
ADE (Antibody-Dependent Enhancement)
A Nature article in September 2020 cautioned the potential risks of ADE (Antibody-Dependent Enhancement) of Covid-19 vaccines3. ADE describes a biological phenomenon where vaccines do not protect the vaccine recipients, but instead the vaccine make it easier for the virus to infect and enter cells and may potentially make the recipient develop more serious disease had they not been vaccinated. In other words, vaccines will not protect these patients and instead when they are infected with the virus, the vaccine will make it worse for these patients.
Previous vaccine attempts have been made towards respiratory coronaviruses SARS-Cov (2002-2003), MERS-Cov (2012) and also Respiratory Syncytial Virus (RSV) all seemed to trigger ADE4,5. ADE has become a serious concern to vaccine deveopment6,7. ADE has been observed in many viruses including HIV8,9, Ebola10,11, Influenza12 in addition to SARS-Cov, MERS-Cov and RSV.
So far there has been no vaccines SARS-Cov, MERS-Cov or RSV vaccines approved. ADE is part of the reason.
Worse, there is evidence to suggest that elderly people may be more prone to develop ADE disease5,13. In other words, the population that needs protection the most is also more likely to develop the serious ADE effects.
Should you get the Covid-19 vaccines?
The million (or maybe billion) dollar question is why nearly half of US residents are not interested in getting the Covid-19 vaccines?
Covid-19 is a serious disease that, compared to flu, transmits more rapidly and has a longer incubation period (2-14 days for Covid-19 compared to 1-4 days for flu), these 2 factors make Covid-19 spread to more people than flu. Covid-19 also seems to be more serious in some people than influenza. Infection Fatality Ratio (IFR) is one of the metrics to measure the severity of a disease. It measures the proportion of deaths among all infected individuals. In other words, IFR measures the probability of death if you catch Covid-19.
Using this metric, IFR for Covid-19 is similar to that of influenza and may be even lower, at least for people (Table 1), according to CDC. Another study published at the Annals of Internal Medicine recently also estimates the Covid-19 IFR for people 40 years or younger at 0.01% and for people 60 years or older at 1.71%14, in line with CDC’s estimates. These data show that for most people, esp. young people, Covid-19 is not a more serious disease than an influenza. It’s the older population and the population with immune-compromised conditions that may display more serious symptoms when they catch SARS-Cov2.
Table 1. Infection Fatality Rate (CDC) for Covid-1915 and IFR (WHO) for Influenza16
|Age (years)||Covid-19 IFR15||Influenza IFR16|
For all age groups combined. No Age specific breakdown data.
So, if you are young and generally healthy, and don’t want Covid-19 vaccines, and don’t want to catch Covid-19, or if you catch it, you hope you don’t develop serious diseases, is there anything you can do? I’ll answer these questions in the next article. Stay tuned.
- Shodiya, Z. W., Titilayo. Why So Many Americans Are Skeptical of a Coronavirus Vaccine. Scientific American https://www.scientificamerican.com/article/why-so-many-americans-are-skeptical-of-a-coronavirus-vaccine/.
- Allen, A. Five Important Questions About Pfizer’s COVID-19 Vaccine. Kaiser Health News https://khn.org/news/pfizer-covid-19-vaccine-effectiveness-5-things-to-know/ (2020).
- Lee, W. S., Wheatley, A. K., Kent, S. J. & DeKosky, B. J. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nature Microbiology 5, 1185–1191 (2020).
- Cardozo, T. & Veazey, R. Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease. International Journal of Clinical Practice n/a, e13795.
- Mercola, Joe. How COVID-19 Vaccine Can Destroy Your Immune System. Mercola.com http://articles.mercola.com/sites/articles/archive/2020/11/11/coronavirus-antibody-dependent-enhancement.aspx.
- Tirado, S. M. C. & Yoon, K.-J. Antibody-dependent enhancement of virus infection and disease. Viral Immunol 16, 69–86 (2003).
- de Alwis, R. Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161485/.
- Robinson, W. E., Montefiori, D. C. & Mitchell, W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet 1, 790–794 (1988).
- Robinson, W. E. et al. Antibody-dependent enhancement of human immunodeficiency virus type 1 (HIV-1) infection in vitro by serum from HIV-1-infected and passively immunized chimpanzees. Proc Natl Acad Sci U S A 86, 4710–4714 (1989).
- Takada, A., Watanabe, S., Okazaki, K., Kida, H. & Kawaoka, Y. Infectivity-enhancing antibodies to Ebola virus glycoprotein. J Virol 75, 2324–2330 (2001).
- Takada, A., Feldmann, H., Ksiazek, T. G. & Kawaoka, Y. Antibody-dependent enhancement of Ebola virus infection. J Virol 77, 7539–7544 (2003).
- Ochiai, H. et al. Infection enhancement of influenza A NWS virus in primary murine macrophages by anti-hemagglutinin monoclonal antibody. J Med Virol 36, 217–221 (1992).
- Wu, Fan & Et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. 20.
- Blackburn, J., Yiannoutsos, C. T., Carroll, A. E., Halverson, P. K. & Menachemi, N. Infection Fatality Ratios for COVID-19 Among Noninstitutionalized Persons 12 and Older: Results of a Random-Sample Prevalence Study. Ann Intern Med (2020) doi:10.7326/M20-5352.
- CDC. Coronavirus Disease 2019 (COVID-19). Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html (2020).
- WHO. Coronavirus disease 2019 (COVID-19) Situation Report – 46. (2020).