The Cracks in the Shield


 “Trust everybody, but cut the cards.”
Finley Peter Dunne (1867-1936) and expressed in dialect by his character "Mr. Dooley" in Mr. Dooley's Philosophy (1900), p. 260: "Thrust ivrybody—but cut th' ca-ards."1
COVID-19 vaccine has been launched

“There is good news for you. COVID-19 vaccine launch is imminent! It is just a matter of days now. You must be very excited?”

I was on a telephone call with my old friend JS.2 He had superannuated from the service and was now working with a corporate hospital. Despite being above 60 years of age, he was in the thick of COVID-19 management in his hospital as senior consulting physician.

His answer was a long,”Hmmmmmmmm.” followed by a pause.

I remarked,”You don’t seem very enthusiastic about it!”

He said,”No, No, No. I am very excited that a vaccine has been made. But I don’t know how to respond!” He added after a pause,”My honest answer to your first question is – it’s a very good question.”

I remembered that once JS had told me that the phrase ‘It’s a very good question’, is used by a speaker when he wants to gain some time to think over the answer. I remarked, “I thought you would jump at it. Especially you, since you are working with COVID-19 cases at your age.”

He agreed,”Yes I should. So far I have managed to survive because of personal protective equipment (PPE). Work day in PPE is hell. It will be a big relief if I could work without it.”

I sensed a contradiction in his stance and asked,”Then what is the problem?”

Why are you hesitent?

JS was again silent for some time. Then he said,”The problem is that our medical administrators and decision makers are overwhelmingly committed to provide it as early as possible. The problem is that the vaccine has been declared safe and effective in the media reports without any peer reviewed publication. The problem is what they call emergency use authorization (EUA)!”

I thought I will refute his doubts one by one. I started with the first one and asked, “Isn’t it a good thing that our administrators are so concerned about everyone’s health?”

His voice was sharp this time, “I personally think that their primary aim is to create that perception for getting votes in the next election.”

I was surprised. JS was usually very mild mannered and this was a strong statement coming from him,”Why do you doubt their intentions?”

He turned around to accuse me,”Partly because of you!”

I was surprised, “Why? What have I done?”

He said, “Wasn’t it you who highlighted their repeated attempts to under report cases? Wasn’t it you who talked about the ‘Watchdog with a bone3 and ‘Privileged in pandemic’4 and calling all of them ‘Mr Hyde’?5. And you are not the only one. There are so many other reports that hint at those intentions.”

I stammered, “Don’t go by all the disinformation on the social media! What do you have against the vaccines? Haven’t we eradicated smallpox, a deadly viral disease with effective vaccination?”

Can the vaccine eradicate disease

JS retorted, “We also have an effective vaccine available against another viral disease – hepatitis B for nearly four decades now! Have we been able to eradicate it?”

I answered with another question, “But we do use it and recommend it to all vulnerable populations, don’t we?”

He answered,”That’s because it is cheap and has been proven to be safe after several hundred thousand doses in peer reviewed publications. That has not yet happened with COVID vaccines.”

I poked him, “So, it is a scientific publication that you want!”

JS shot back,”Without peer reviewed research publications, a media assertion is no better than Ayurvedic declaration of miracle cures!”

I reminded him, “But you remember the Lancet paper6 that suggested that MMR vaccine could lead to a new syndrome of gastrointestinal pathology and neurodevelopmental regression?”

JS had a knack of remembering such trivia, “Well, you cannot malign scientific medicine by quoting this example. This report was based on 12 cases where a parent or a physician thought that the child’s autistic behavior worsened after they were given an MMR vaccine. The study had limitations that were pointed out by others.7 The problem was the news media! The paper generated intense media and public attention resulting in perception among many that vaccines caused autism! It decreased MMR vaccination coverage, particularly in the United Kingdom, with resultant re-emergence of measles disease and deaths.”

MMR vaccine and autism

I added, “It wasn’t an isolated report. Another study8 reinforced the perception that vaccination-was-related-to-autistic-entercolitis hypothesis.

JS knew about it too, “Yes, I know. It had taken years of painstaking research to refute the second paper too.”

I said, “It had turned a generation of young mothers against MMR or any other vaccine. Although the article was retracted by the journal 12 years later, because of improprieties in subject recruitment and financial conflicts of interest.9,10, 11,12 However, the doubts it raised have lingered in many minds.”

JS was unmoved, “It was selective media coverage that formed the public opinion before the medical fraternity could declare its opinion.”

I agreed, “More definitive evidence came much later. It was a meta-analysis that concluded that MMR vaccine is not associated with an increased risk of autism 13 The evidence for a possible association between MMR vaccine and autism was also extensively reviewed by three committees of the National Academy of Medicine.14 All have concluded that MMR vaccine does not cause autism.”

A little knowledge is a dangerous thing

JS reiterated, “Well, when the media takes it upon itself to teach medicine to masses, such disasters will happen. People had started staying away from vaccinations during that decade!”15,16

I suggested, “Is that the reason why there are doubts in your mind about COVID vaccine too?”

JS answered, “AC, I belong to the generation that has prescribed the first generation anti-rabies vaccine when we were young. Those days we did what we were told. And I have seen a few of my healthy vaccine recipients develop crippling demyelinating neurological diseases. It was a terrible experience leaving one hopelessly guilt ridden.”

I added, “But that has become exceptionally rare with currently used vaccines.”

He answered, “Yes, but it is because of prolonged and stringent testing and screening for safety. A precaution we are planning to dispense with for COVID vaccines!”

I asked, “Why do you say that?”

JS said, “Vaccine development is a long, complex process, often lasting 10-15 years and involving a combination of public and private involvement.17 The vaccine development passes through exploratory stage, preclinical stage, followed by Phase 1, 2 and 3 clinical trials, before they come for regulatory review. In USA, for example, FDA 18has established a Vaccine Adverse Event Reporting System or VAERS 19 in 1990. On an average about 30,000 events are reported each year to VAERS. Between 10% and 15% of these reports describe serious medical events that result in hospitalization, life-threatening illness, disability, or death.

I asked, “What happens then?”

Safety is paramount

He said, “Another organisation CDC20 then monitors and evaluates them with computer programmes such as vaccine safety datalinks and Rapid Cycle Analysis to study associations between adverse events and vaccination.”

I poked a question, “All this has not been done for COVID-19 vaccine?”

JS replied, “Who knows? The whole process of 10-15 years has been compressed to less than a year and every manufacturer is pushing for EUA!”21

I questioned, “What does EUA involve?”

JS said,”It is to say that in emergency we can authorise use of a drug, device or test without stringent evidence to support its use!”22,23

I asked,”Are provisions of EUA used frequently by the regulatory authorities?”

JS declared,”It is rarely used. It was used for the first time in 2009, when Tamiflu was authorised for the H1N1 epidemic. Ir was followed by a huge uproar and some even called it a scandal.”24

Emergency use authorisation(EUA)

I asked, “Covid-19 is a global pandemic. So, the ‘emergency’ rule should apply to it?”

JS was sure, “It does. So far all the EUA given for use of medicines for COVID-19 had to be revoked as they did not benefit patients. Examples are hydroxychloroquine, remdesivir and plasma therapy. In our setup, where patients have to pay for treatment, it has led to significant monetary loss to the patients. Basically we learnt about its uselessness at the expense of the patient. Vaccine, I believe, is a more risky preposition!”

“Why?” I asked.

JS replied, “Because it will be given to millions of ‘normal’ people! We need to be 100% sure about its safety. Learning about its adverse effects in a post-approval surveillance systems,25,26,27 will turn out to be too expensive.

I remarked,”Well EUA for medicines was done in good faith!”

JS shook his head, “Unfortunately, political pressures28 may have led to the FDA making earlier decisions that were not well-supported by science. With a Covid-19 vaccine, the FDA has a chance to win back the public’s trust by being honest to itself. Though it seems unlikely at present.29 Besides, a subpar vaccine could give people a false sense of security, to abandon other public health measures. 

I was wondering, “If the vaccine is provided free, is it alright?”

JS laughed,”Despite their claims to the contrary, pharmaceutical companies are being run only for profits.30 If Governments make it free, it means the taxpayers will pay. No, even if it is free, the question of safety and efficacy needs to be ascertained.”

I asked, “Doesn’t EUA take into account that aspect?”

JS said, “AC, every vaccine developer is approaching the manufacturing process differently. Several candidate vaccines being tested have used a new technology (Example: RNA vaccines), which has not yet been used on human beings in the past. On top of that, everyone is now seeking the EUA! It makes me a bit uncomfortable.”31

Will this vaccine restore the trust of lay public in medical fraternity?

What about serious adverse reactions

I wasn’t sure I understood his discomfort,”But what is wrong with the EUA?”

JS replied,”Firstly, the EUA has been sought in many countries without completing phase III trials. Phase 1/II trials are not powered to detect less common (often very serious) adverse reactions to vaccines and the risk of those developing will remain on larger experience.

I interjected,”And?”

He remarked,”Even early phase I/II experience has thrown up serious side effects with COVID-19 vaccine.” 32,33,34,35

I saw his point,”I see. Anything else?”

JS continued,”Secondly, if trials only test for immunogenicity, the risk of immune enhancement of the disease, (the paradoxical risk of more severe disease in individuals who are vaccinated) has not been assessed and may surface only after public use.36 In fact there are report that suggest its plausibility.37

I said, “So the main worry is safety!”

Methodological Problems

JS added,”Yes, Trial machinery in India is, as it is, error prone and does not inspire confidence.38

I didn’t like his comment,”You cannot say that on basis of isolated reports.”

He said, “Okay, but there are more problems. Vaccines have been tested in young population only. This data may not represent the response of elderly population which is more vulnerable to adverse outcomes. Vaccines may need to be tweaked for a special population. Similar modifications were needed for the flu vaccines.39

I too was now getting convinced about his doubts about the vaccine, “Anything else?”

JS took a deep breath and added,”I wish it was all. We already know that immune response to human Coronaviruses is short lived – a few weeks to months.40,41,42 It has also been shown that detectable antibodies may not be protective.43  Second infection by SARS-COV-2 in the same individual is well known.44 Second infections may even be more severe!”45

I now understood the gravity,”It means manufacturing companies are permitted to sell the vaccine, but its use will be an extended research trial at the expense of the public!”

Ethical issues

JS said,”Exactly! And then, there are more ethical issues. Suppose Indian vaccine trials are still going on when US vaccines are marketed. Will you give the option to the public to buy the US vaccine and opt out of trial? In the latter case, Indian vaccine trials can never be completed. It will be unethical to deny the trial participants the benefit of a proven vaccine!; especially to those who might be assigned to the placebo arm”46

I remarked,”So you don’t trust the vaccines being given EUA?”

He replied, “I am a small man. The academic community has declared that lack of confidence is natural when there is lack of transparency.”47

I asked, “Is there no transparency?”

JS said,”A few manufacturers  like Moderna, Pfizer, AstraZeneca, and Johnson & Johnson have been forced by the academic community to share their clinical-trial protocols for vaccine candidates in phase III clinical trials publically. There are some other concerns too. For example, many vaccine trials are looking to “prevent mild disease” (as primary endpoint) rather than “protection against severe disease and death”.48

I asked, “What do you think should be done?”

Way-out: Transparency

JS had clear requirements, “Firstly, the evaluation criteria, process for evaluating EUA vaccine candidates, and data submitted for evaluation should be made transparent to the public. Secondly, EUA decisions for COVID-19 vaccines should require a favourable benefit–risk ratio based on available quality, safety, and performance data.49 

I asked, “Anything else?”

JS carried on, “Thirdly, since emergency use authorisations are designed for circumstances when the public is probably willing to tolerate less certainty about the efficacy and safety of medical products,50 exactly what constitutes a favourable benefit–risk ratio should be informed by engaging relevant communities. Finally, an accountable system of ethical and regulatory oversight and monitoring that aims to satisfy these conditions should guide EUA for COVID-19 vaccines.“51

I said,”I am told one company has released its data for scrutiny.”52

JS replied, “I know. Just before EUA was announced, we had a news that said ‘White House chief of staff Mark Meadows on Friday pressed Food and Drug Administration chief Stephen Hahn to grant an emergency use authorization for Pfizer’s coronavirus vaccine by the end of the day or face possible firing.’53

Will I take the vaccine tomorrow?

“So, will you take the vaccine if offered to you tomorrow?” I asked again.

JS declared his intention ver clearly,”I will wait for the results of first one million cases to be published before I take it.”

He was a die hard evidence based medicine fan and had reflected the mood of sceptics among the medical fraternity who may not rush into taking the vaccine. I was a little more flexible and would have taken the vaccine for larger good. But the facts brought out by JS, combined with some social media chatter (see figure below), were forcing me to have second thoughts.

As we moved towards more personal pleasantries in our long conversation, I was thinking that public health emergencies were a real waterloo for the research ethics.54 Exposure or challenge studies have their own ethical concerns.55 There were also concerns about approvals being rushed, fears of political interference, undue pressure on regulatory authorities to approve a vaccine before data show that it is effective and safe. Add to it the suspicions about the vaccine industry and an outbreak of vaccine misinformation. All these factors are combining to erode the public’s trust in the vaccine development and approval processes.56 

Let’s hope that the shield will protect us despite all the cracks.

Two interesting social media forwards on the subject. First one pokes fun at people expecting a miracle injection, while second one cautions people against rushing for it.
Post script

The author has tried to highlight the fears and limitations associated with a rushed vaccine production process. It does not in any way reduce the respect he has for thousands of professionals who have burnt the midnight oil to make a vaccine possible in a record time.


2 Anand AC. Swami Ramdev and scientific medicine: losing is fine, but the lesson should not be lost! Natl Med J India. 2007;20(5):256-9.
6 Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, et al. 1998 Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 351(9103):637–41
7 Chen RT, DeStefano F. Vaccine adverse events: causal or coincidental? Lancet 1998; 351(9103):611–12
8 Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, et al. 2002 Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Mol. Pathol 55(2):84–90
9 Lancet. 2010 Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 375(9713):445
10 DeStefano and Shimabukuro TT. The MMR Vaccine and Autism. Annu Rev Virol. 2019; 6(1): 585-600
11 Dyer C. Lancet retracts Wakefield’s MMR paper. BMJ 2010; 340:c696
12 Deer B. How the case against the MMR vaccine was fixed. BMJ 2011; 342:c5347
13 Taylor LE, Swerdfeger AL, Eslick GD. 2014 Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Vaccine 32(29):3623–29
14 a. IOM (Inst. Med. 2001 Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. Washington, DC: Natl. Acad; b. IOM (Inst. Med.). 2004 Immunization Safety Review: Vaccines and Autism. Washington, DC: Natl. Acad; c.IOM (Inst. Med.). 2012 Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: Natl. Acad.
15 Siddiqui M, Salmon DA, Omer SB. 2013 Epidemiology of vaccine hesitancy in the United States. Hum. Vaccin. Immunother 9(12):2643–48
16 DeStefano F, Shimabukuro TT. The MMR Vaccine and Autism. Annu Rev Virol. 2019 Sep 29;6(1):585-600. doi: 10.1146/annurev-virology-092818-015515.
18 Food and Drug Administration, a federal agency of the Department of Health and Human Services, USA
20 Centers for Disease Control and Prevention is a national public health institute in the United States
29, 53
31 Krause PR, Gruber MF. Emergency use authorization of Covid vaccines – safety and efficacy follow-up considerations. N Engl J Med. 2020 Oct 16.Doi: 10.1056/NEJMp2031373.
32 Anonymous. Claims and counterclaims over alleged adverse reaction in covid-19 vaccine in India.BMJ 2020;371:m4734
36 Takada A, Kawaoka Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol. 2003 Nov-Dec;13(6):38798. Doi: 10.1002/rmv.405.
37, 40 Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Rydyznski-Moderbacher C,et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell. 2020 Jun 25; 181 (7): 1489-1501. e15. Doi: 10.1016/j.cell. 2020.05.015.
39 Wagner A, Weinberger B. Vaccines to prevent infectious diseases in the older population: immunological challenges and future perspectives. Front Immunol. 2020 Apr 23;11: 717. Doi: 10.3389/fimmu.2020.00717.
41 Regalado A. What if immunity to Covid19 doesn’t last? MIT Technology Review. 2020 Apr 27. Available from:
43 Callow KA, Parry HF, Sergeant M, Tyrrell DA. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990 Oct;105(2):435–46. Doi: 10.1017/s0950268800048019.
44 Iwasaki A. What reinfections mean for COVID-19. Lancet Infect Dis. 2020 Oct 12. Corrected Nov 6. Available from:
47 Editorial. COVID vaccine confidence requires radical transparency.Nature. 2020 Oct; 586(7827):8. Doi: 10.1038/d41586-020-02738-y.
48 Vashishtha VM, Kumar P. Emergency use authorisation of Covid-19 vaccines: An ethical conundrum. Indian Journal of Medical Ethics Online First Published November 26, 2020; DOI: 10.20529/IJME.2020.122
49 Dal-Ré R, Caplan AL, Gluud C, Porcher R. Ethical and Scientific Considerations Regarding the Early Approval and Deployment of a COVID-19 Vaccine. Ann Intern Med. 2020 Nov 20:M20-7357. doi: 10.7326/M20-7357. Epub ahead of print. PMID: 33216636; PMCID: PMC7713906.
50 WHO. Emergency Use Assessment and Listing Procedure (EUAL) for candidate vaccines for use in the context of a public health emergency. July 7, 2015.
51 Smith MJ, Ujewe S, Katz R, Upshur REG. Emergency use authorisation for COVID-19 vaccines: lessons from Ebola. Lancet. 2020 Nov 28;396(10264):1707-1709. doi: 10.1016/S0140-6736(20)32337-0. Epub 2020 Nov 5. PMID: 33160452.
54 Solomon S. Public health emergencies: research’s friend or foe?. Am J Bioeth. 2013;13(9):21-23. doi:10.1080/15265161.2013.816582
55 Jamrozik E, Selgelid MJ. COVID-19 human challenge studies: ethical issues. Lancet Infect Dis. 2020;20(8):e198-e203. doi:10.1016/S1473-3099(20)30438-2
56 Koirala A, Joo YJ, Khatami A, Chiu C, Britton PN. Vaccines for COVID-19: The current state of play. Paediatr Respir Rev. 2020;35:43-49. doi:10.1016/j.prrv.2020.06.010



  1. Shyam Tewari said:

    At the end of the day, should the conclusion be drawn that one should not rush for the early vaccination and wait for the response in masses post inoculation.

    19 December 2020
  2. Lt Gen Akhil Nagpal Retd said:

    Dear Admiral
    Many thanks for flagging this very contentious yet contemporary issue in a very balanced manner.
    I totally identify with and share the concerns of JS which are genuine. While the global scientific community needs to be commended for the good work done in record time it is the same community which seems to succumb to the dictates of the political masters who have their own axe to grind. The regulatory bodies have also ended up playing to the gallery. EUA seems to be the norm.
    The multitude of vaccines on different platforms, all claiming upwards of 90% efficacy and coinciding timings of declaring success seems nothing short of a fairy tale. Only hope it ends ” happily after”.
    Closer home, Iam uncomfortable about the Chennai case which may have been brushed under the carpet. Temporal causality was ruled rather summarily.
    Would prefer to be a doubting Thomas and wait out with continuation of Covid appropriate behaviour.
    Thanks and regards.

    20 December 2020
  3. Sankar prasad Gorthi said:

    Dear Sir The dreadful possible post vaccinial complications demand long follow up studies before according approval for public use. Straight away launching a Phase IV effectiveness study in public may lead to devastating consequences.

    20 December 2020

    COVID19 and 2020 has left me a bit confused and disoriented.
    We had the HCQ story followed by Remdesivir and various immune therapies and finally the sublime steroids and anticoagulation which my have save the day.
    From best practices to NEXT practices.
    From allopathy to mixopathy.
    Fast tracking therapies using big data to anecdotal stand alone.
    Now the VACCINE RACE.
    I just hope this provides us breathing time to keep our SPO2 above 94.
    Running a 400 bedded centre in a rural medical College cannot give us much liberty beyond steroids anticoagulation and oxygen.
    Cheers to our metro – rural paradigm.
    The shift is slower than a seismic shift.
    Glad the amygdala with the admiral who has been our teacher from 1979 is sailing in a direction from younger lot to wear their thinking caps.
    Happy 2021

    20 December 2020

    Very eloquent combination of the scientific logic and the art of communicating. Nothing new for AC Anand Sir.
    Besides the points brought out very appropriately and with which I am in full agreement, there is one more doubt that has always been haunting me regarding COVID vaccine, maybe since I am from epidemiology and public health. While assessing vaccine efficacy, the primary end point is always “protection from the target disease” comparing the vaccinated with unvaccinated subjects. This does not seem to be the case with the COVID vaccines in which the primary end point seems to be development of some measurable titre of immunoglobulins. That itself throws open plenty of questions unless we are already fully convinced with evidence that presence of some measurable level of humoral immunity is equivalent to protection from this disease in question.
    Once again, Sir, compliments for bringing out this issue of “hesitancy to take vaccine among healthcare community ” in a very poignant manner.

    20 December 2020
  6. ganesh k said:

    It is unsurprising that skepticism is to the fore. Circumspection is a casualty at warp speed. I always commend Taiwan who just effectively blocked Covid19 transmission by mass supply and mandating of masks! This is far more cost effective than any vaccine bet right now. Anand sir has chosen to not point out Oxford’s churlish explanations for how they stumbled on their first half dose more effective vaccination scheme! JS or AC both are indulging in an adult conversation, which right now is very difficult to have in this pandemic frenzy! The perils are clear. Still we push our luck and move headlong with RNA fragment vaccines as of now! May Hippocrates and his Oath Takers be bailed out from this Darkest Hour!

    20 December 2020
  7. Nicely Elucidared Sir,

    The best way to be safe from Covid is to keeepup our immunity. QED.

    22 December 2020
  8. Brig S M Garg said:

    Excellent Site. Since joined today let me read all first as time permits . Admiral AC sir is well articulated writer on medical issues and issues affecting homo sapiens today. Regards Sir

    24 December 2020
  9. Lt Gen SD Duhan said:

    Skewed Th1 and Th2 responses seen with vaccines with cytokines adjuvants highlight the possible adverse effect of the vaccine with increase in other respiratory infections noted in veterinary coronavirus vaccines and animal models of SARS-CoV and MERS-CoV infections.
    N Engl J Med 2020; 383:1920-1931
    DOI: 10.1056/NEJMoa2022483

    Unique Th1/Th2 Phenotypes Induced during Priming and Memory Phases by Use of Interleukin-12 (IL-12) or IL-28B Vaccine Adjuvants in Rhesus Macaques ▿
    Matthew P. Morrow,1 Jian Yan,1 Panyupa Pankhong,1 Bernadette Ferraro,1 Mark G. Lewis,2 Amir S. Khan,3 Niranjan Y. Sardesai,3 and David B. Weiner1,*

    31 December 2020

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