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Covid-19: FDA authorizes Moderna vaccine as US starts vaccinating health workers

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4924 (Published 21 December 2020) Cite this as: BMJ 2020;371:m4924

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COVID-Vaccinations: Why it Matters to Know the Real Effectiveness

Dear Editor,

As argued in previous responses [1][2][3], the current COVID vaccines' supposed effectiveness of 95% may be a substantial overestimation. Even so, pretending such effectiveness may bring a placebo effect to vaccine recipients heightening their chances of staying healthy or not becoming severely ill. This may be a valid reason for indulging the high estimate, even if incorrect. Moreover, with lower effectiveness, people's getting vaccinated may still be worthwhile. The high estimate will motivate people to receive the vaccine. Why should we even find out whether the effectiveness is less? And isn't the outcome the same in what needs to be done?

We see reasons leaving no doubt that it matters:

• Science as a value of Western enlightenment, more or less worldwide accepted.
• Judicial: informed consent, whereby information should be as rational and open as possible.
• Accurate information can lead to better vaccine developments and to vaccine tweaking of the present one. We recommended treatment assumption testing. [2]
• People's behavior change (including healthcare personnel) depends on correct information.
• If part of the vaccines' effectiveness is actually a placebo effect, we should know more about placebo and the mind's influence on COVID. It is better to discuss this openly.
• Resource allocation, leading to more attention for cost-effective solutions, such as tracing.
• With lower effectiveness of the vaccine at the start, we may need to redo the whole vaccination effort sooner. It's important to be optimally prepared, even though or precisely because much remains inconclusive at the moment: How well do the vaccines diminish morbidity and mortality? How long do they work? To what degree do they lower infectiveness?
• Likewise, more is needed to achieve herd immunity.
• Economic costs: optimal business decisions at micro and macro scales depend on correct information.
• This helps us in being better prepared for the next pandemic and other future worldwide calamities.
• Lower effectiveness may lead to a greater danger of virus vaccine resistance. This is an additional reason not to give a single dose. Compare this with the correct use of antibiotics.

+ If substantially lower effectiveness becomes apparent after some time:

• Deontological: People may get ill by not adhering to other safety measures. If people even die through being careless (from untowardly thinking to be safe), their loved ones feel immensely cheated. Who will pay for indemnification?
• People may lose confidence in vaccines, their physicians, medicine, or even science in general.
• A loss of confidence in science may have unforeseen cultural effects. Many anti-science groups are eager to take advantage.
• This loss of confidence may lead to a huge nocebo effect and mass psychogenic illness upon being vaccinated. Such psychogenic illness has been described repeatedly in cases of mass vaccination. [4][5][6]
• The loss of confidence may lead to post-traumatic stress immediately and after years.
• There may be huge demotivation, loss of hope, growing despair.
• This can additionally hurt the economy worldwide through many misinformed business decisions.

Also, we want to point to the obvious fact that long-term safety has not been investigated. The past shows unforeseen eventualities. E.g., vaccination against former SARS in mice, including one with an rDNA S protein vaccine, led to pulmonary eosinophil immunopathology on a challenge with live SARS virus, suggesting hypersensitivity to SARS-CoV components. The authors concluded that "Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated… The concern arising from the present report is for an immunopathologic reaction occurring among vaccinated individuals on exposure to infectious SARS-CoV, the basis for developing a vaccine for SARS. Additional safety concerns relate to effectiveness and safety against antigenic variants of SARS-CoV and for the safety of vaccinated persons exposed to other coronaviruses." [7] The same direction has been noted with MERS, [8] but not with influenza vaccines. [7] In cost-benefit ratio, a lower benefit is more important in the light of long-term danger-in-not-knowing. Without falling into anti-vax paranoia, the fact is that we cannot have certainty in this regard at present, even more so since the virus keeps mutating.

If vaccinations turn out to be effective only in a lower range, this will not be readily apparent unless it gets related to flaws in the vaccination studies. We have argued previously about a major flaw in this specific type of study, generally. [1][2][3] At present, we advise to be vigilant. The study results are less certain than generally thought.

At present, the world embarks upon an immense prospective cohort study on a large part of its entire human population. In this prospective study, confounding factors may interfere with a clear view on effectiveness. In case doubts about effectiveness arise, several arguments may be brought to bear as possible explanations:

• Seasonality of the virus: As summertime positive evolution may be attributed to the vaccination's success, a lack of success may be attributed to the fall and wintertime. (The opposite can also happen.)
• New variants show here and there, possibly being more infective or vaccine-resistant.
• People don't adhere to other safety measures.
• The virus' has shown 'strange behavior' in the past. Note: Part of such behavior may have human rather than viral causes.
• Coincidence, or yet-to-be-found factors in the environment.
• The immune response to the vaccine attenuates quicker than hoped. This can go together with lower effectiveness from the start.

Vested interests may push towards accepting these arguments too readily, such as 'big pharma' financially and the ubiquitous unwillingness to see the mind as a causal factor.

We urge for truth and transparency all the way through, even if this means that people can profit less from the vaccines' possibly substantial placebo-effect. [1][2][3] The balance will eventually be positive.

Dr. Jean-Luc Mommaerts, M.D., M.A.I., - Ph.D. Jean-Luc.Mommaerts@vub.be - Vrije Universiteit Brussel (Free University Brussels)
Prof. dr. Dirk Devroey, M.D., Ph.D., Dean of Medicine & Farmacy - dirk.devroey@vub.be - Vrije Universiteit Brussel (Free University Brussels)

Bibliography
[1] Jean-Luc Mommaerts and Anne-Mieke Vandamme, "Blindness breach powered by inadvertent placebo proneness may confound COVID-19 vaccination study results", 23 December 2020, https://www.bmj.com/content/371/bmj.m4924/rr-0
[2] Jean-Luc Mommaerts, Dirk Devroey, Anne-Mieke Vandamme, "The Importance of Testing for Blindness in COVID-19 Vaccination Trials", 02 January 2021, https://www.bmj.com/content/371/bmj.m4924/rr-5
[3] Jean-Luc Mommaerts, Dirk Devroey, "COVID Vaccination Studies: From Double-Blind to Hardly-Blind?", 04 January, 2021, https://www.bmj.com/content/371/bmj.m4924/rr-6
[4] Yang TU, Kim HJ, Lee YK, Park YJ. "Psychogenic illness following vaccination: exploratory study of mass vaccination against pandemic influenza A (H1N1) in 2009 in South Korea." Clin Exp Vaccine Res. 2017 Jan;6(1):31-37. doi: 10.7774/cevr.2017.6.1.31. Epub 2017 Jan 25. PMID: 28168171; PMCID: PMC5292354.
[5] Simas C, Munoz N, Arregoces L, Larson HJ. "HPV vaccine confidence and cases of mass psychogenic illness following immunization in Carmen de Bolivar, Colombia." Hum Vaccin Immunother. 2019;15(1):163-166. doi: 10.1080/21645515.2018.1511667. Epub 2018 Sep 7. PMID: 30118381; PMCID: PMC6363158.
[6] Kharabsheh S, Al-Otoum H, Clements J, Abbas A, Khuri-Bulos N, Belbesi A, Gaafar T, Dellepiane N. "Mass psychogenic illness following tetanus-diphtheria toxoid vaccination in Jordan." Bull World Health Organ. 2001;79(8):764-70. Epub 2001 Oct 24. PMID: 11545334; PMCID: PMC2566491.
[7] Tseng CT, Sbrana E, Iwata-Yoshikawa N, et al." Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus." PLoS One. 2012;7(4):e35421. doi:10.1371/journal.pone.0035421
[8] Agrawal AS, Tao X, Algaissi A, et al. "Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on a challenge with live virus." Hum Vaccin Immunother. 2016;12(9):2351-2356. doi:10.1080/21645515.2016.1177688

Competing interests: No competing interests

Competing interests: No competing interests

06 January 2021
Jean-Luc Mommaerts
Medical doctor, researcher
Dirk Devroey (VUB)
Vrije Universiteit Brussel
Oude Godstraat 200