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Letters Covid-19: late stage vaccine candidates

Unwarranted optimism about vaccine efficacy

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4918 (Published 23 December 2020) Cite this as: BMJ 2020;371:m4918

Rapid Response:

COVID-19 Pandemic and COVID-19 Vaccines as the Panacea: not yet the ‘Magical Pharmaceutical Intervention’

Dear Editor

The recent ‘Communication’[1] in The BMJ is instructive and, indeed, calls for caution regarding ‘COVID-19 Vaccines’: ‘Unwarranted optimism about vaccine efficacy’! The ‘COVID-19 Vaccines’ appear to be inappropriately touted as near-‘Pharmaceutical Magic Gun’ against the ‘COVID-19 Pandemic’!! To be sure, the availability of ‘Approved COVID-19 Vaccines’ is not an invitation to vacate the ‘Non-Pharmaceutical Interventions (NPIs)’; The ‘Interventions that Work’ against the ‘COVID-19 Pandemic’[2]! We are, indeed, cautioned against ‘Unwarranted Optimism’ concerning ‘COVID-19 Vaccines’ as the long-awaited ‘Programmatic Intervention’ which may not have the ‘Magic Wand’ or be envisioned as the ‘COVID-19 Intervention’ with the ‘Midas Touch’ in the ‘Global Fight’ against the ‘COVID-19 Pandemic’!!

It was reported that the ‘Phase III Clinical Trial’ of the ‘Oxford-AstraZeneca Candidate Vaccine’ produced intriguing results still baffling Immunologists labouring hard trying to understand and explain the rather ‘Unexpected’ or ‘Unusual’[3]! In the ‘Phase III Clinical Trial’, a group received the ‘Intended Regimen’ of ‘2 Doses’ and a second group received ‘2 Doses with a Reduced 1st Dose’1!! It is reported that the ‘Reduced 1st Dose Regimen’ was ‘90% Effective’ compared with ‘62% Effectiveness’ for the ‘Intended Regimen’!! Indeed, the ‘Reduced 1st Dose Regimen’ was an ‘Error in Preparation’ and not as a ‘Study Design’ with proper ‘Research Question’ and ‘Research Hypothesis’!! Recall always that consistent with strict ‘Robust Research Governance Principles’: ‘No Research Question, No Research’!!! These strict ‘Robust Research Governance Principles’ MUST be upheld to avoid the enlarging unacceptable ‘Body’ of ‘COVID-19 Research Wastes’[4-8] and also to protect against the ‘Vulnerabilities’ of Science[9]!! Reports from ‘Study Designs’ without a ‘Research Question’ and a ‘Research Hypothesis’ should be viewed with extreme caution[1,8]!!

A ‘Communication’[10] recently critically evaluated a ‘Report’ on the ‘Pfizer-BioNTech Candidate Vaccine Clinical Trials’ with intriguing disposition! Of the 36,523 Healthy Subjects, 18, 198 received the ‘Candidate Vaccine’ while 18, 325 received Placebo. A total of 170 Participants with ‘COVID-19 Manifestations’ were recorded: 162 among ‘Placebo Group’ and 8 in the ‘Candidate Vaccine Group’. Also 9 out of 162 (5.56%) in the ‘Infected Placebo Group’ were severely ill compared with 1 out of 8 (12.5%) in the ‘Vaccinated Group’; a very disturbing critique[10]!! Additionally, there was no determination of ‘SARS-CoV-2 Antibodies’ in evaluating the ‘Candidate Vaccine Efficacy’[10] as 40% of ‘COVID-19 Cases’ may be ‘Asymptomatic’[11]! The ‘COVID-19 Antibodies’ are also reported to be dysfunctional, suboptimal and with short-lasting Immunity[12]!! Also, the ‘Confounding Influence’ of ‘Social Distancing’ on the reported results was not considered in evaluating the ‘Candidate Vaccine Efficacy’[10]!! Yet another ‘Confounding Variable’ that was not considered in the ‘Clinical Trial’ is the ‘ABO Blood Group’ of the ‘Clinical Trial Participants’ as ‘Blood Group O’ is reported to be associated with reduced likelihood of ‘Severe Illness’ and ‘Death’ in ‘COVID-19 Cases’[13]!!! This is the importance and relevance of ‘Good Study Design’ situate with strict ‘Research Governance Principles’ for ‘Valid Conclusions’ to avoid ‘COVID-19 Research Wastes’, more particularly so, concerning ‘Candidate Vaccine Phase III Clinical Trial’ with envisioned ‘Outcomes’ and ‘Determinant Programmatic Interventional Impact’ on the ‘COVID-19 Pandemic’!!!

Indeed, another ‘Study Report’ on the ‘SARS-CoV-2 Antibodies’ and ‘Protective Efficacy’ against ‘COVID-19’, did not administer the ‘Antibodies’ to moderately and severely affected ‘COVID-19 Cases’ with monitored ‘Outcome/ End-Point’[14]! This is a ‘Study Design Requirement’ for ‘Valid Conclusions’ on the evaluation of ‘SARS-CoV-2 Antibodies Efficacy’!! Too many ‘Unresolved Issues’ continue to plague the ‘SARS-CoV-2 Antibodies’ in the ‘Global Fight’ against the ‘COVID-19 Pandemic’[15-24]!! There have been calls for caution in the rush towards the ‘Vaccines Marathon Finish Line (Vaccine Approval)’ to assure ‘Vaccine Efficacy’, ‘Vaccine Safety’, ‘Vaccine Uptake’ and successful ‘Vaccination’ in the ‘Global Fight’ against the ‘COVID-19 Pandemic’!!!

This brief ‘Communication’ is a modest ‘Contribution’ to the evolving ‘COVID-19 Pharmaceuticals Conversation’ as the ‘Envisioned Panacea’ in the ‘Global Fight’ against the ‘COVID-19 Pandemic’! There should be strict compliance with the prescribed NPIs even with ‘Approved Vaccines Availability’ and ‘Successful Vaccination Programmes'!! The envisioned ‘Approved Vaccines’ should be regarded with ‘Cautious Optimism’ and not ‘Unwarranted Optimism’ with downing of guards particularly with respect the ‘COVID-19 Pandemic Mitigation Measures’ that work!!!

REFERENCES
1. Skegg D, Pearce N. Unwarranted optimism about vaccine efficacy. BMJ 2020; 371:m4198
2. Eregie CO. COVID-19 Pandemic and COVID-19 Vaccinations: Beyond the ‘Vaccines Marathon Finish Line’; The Unfolding ‘Works in the Work’ https://www.bmj.com/content/372/bmj.n24/rr-1 of 20th January 2021
3. Mahase E. Covid-19: What do we know about the late stage vaccine candidates? BMJ 2020; 371:m4576
4. Clinical Trials.gov. History of changes for study. NCT04280705, 1 May 2020. https://clinicaltrials.gov/ct2/history/NCT04280705?A=10&B=15&C=Side-by-S....
5. Yan W. Coronavirus tests science’s need for speed limits. New York Times 2020 Apr 14. https://www.nytimes.com/2020/04/14/science/coronavirus-disinformation.html
6. Hoffmann T, Glasziou P. What if the vaccine or drugs don’t save us? Plan B for coronavirus means research on alternatives is urgently needed. The Conversation, 21 Apr 2020. https://theconversation.com/what-if-vaccine-or-drugs-dont-save-us-plan-b...
7. Glasziou PP, Sanders S, Hoffmann T. Waste in covid-19 research. BMJ 2020; 369:m1847
8. Eregie CO. COVID-19 Pandemic: The multifaceted picture of compromised COVID-19 research and the COVID Phenomenon’. https://www.bmj.com/content/369/bmj.m1847/rr-12 of 10th June 2020
9. Eregie CO. COVID-19 Pandemic and vulnerability of science to assault: Imperatives to uphold research governance principles. https://www.bmj.com/content/372/bmj.n12/rr-4 of 22nd January 2021
10. Batarseh KI. The Efficacy of Pfizer/ BioNTech Vaccine on COVID-19: The Devil is in the Details. https://www.bmj.com/content/371/bmj.m4198 of 11th January 2021
11. COVID-19 Pandemic Planning Scenarios. CDC. Updated September 10, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html.
12. Batarseh KI. Plasma from healthy young people and human thymopoiesis as potential therapy against COVID-19: further and concrete up-to-date scientific support. BMJ. Published Online August 13, 2020. https://www.bmj.com/content/370/bmj.m2722/rr-4 of 13th August 2020
13. Zietz M, Zucker J, Tatonetti P. Associations between blood type and COVID-19 infection, intubation and death. Nat Commun 11, 5761 (2020). Published Online November 13, 2020. https://doi.org/10.1038/s41467-020-19623-x.
14. Polack F, Thomas S, Kitchin N et al. Safety and efficacy of the BNT162b2 Mrna Covid-19 vaccine. NEJM. Published Online December 10, 2020. Doi:10.1056/NEJMoa2034577
15. Lisboa Bastos M, Tavaziva G, Abidi SK et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ 2020; 370:m2516
16. Premkumar L, Segovia-Chumbez B, Jadi R et al. The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol 2020; 5:eabc8413
17. Duong YT, Wright CG, Justman J. Antibody testing for coronavirus disease 2019: not ready for prime time. BMJ 2020; 370:m2655
18. Antibodies Brouwer PJM, Caniels TG, Straten K et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. https://science.sciencemag.org/content/2020/06/15/science.abc5902
19. Deeks JJ, Dinnes J, Takwoingi Y, et al. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev 2020; 6:CD013652
20. Eregie CO. Covid-19 Pandemic, SARS-CoV-2 antibodies and testing: Still searching for more facts. https://www.bmj.com/content/369/bmj.m2584/rr of 16th July 2020
21. Liu A. Regeneron scales up manufacturing, eyes human tests of COVID-19 antibody cocktail in June. Fierce Pharma. 5 May 2020. https://www.fiercepharma.com/pharma/regeneron-scales-up-manufacturing-ey...
22. US Food and Drug Administration. Independent Evaluations of COVID-19 Serological Tests. FDA, 2020 https://open.fda’gov/apis/device/covid-19serology/
23. Branda JA, Body BA, Boyle J et al. Advances in Serodiagnostic Testing for Lyme Disease Are at Hand. Clin Infect Dis 2018; 66:1133-9
24. Andersson M, Low N, French N et al. Rapid roll out of SARS-CoV-2 antibody testing-a concern. BMJ 2020; 369:m2420

Professor Charles Osayande Eregie,
MBBS, FWACP, FMCPaed, FRCPCH (UK), Cert. ORT (Oxford), MSc (Religious Education),
Professor of Child Health and Neonatology, University of Benin, Benin City, Nigeria.
Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria.
UNICEF-Trained BFHI Master Trainer,
ICDC-Trained in Code Implementation,
*Technical Expert/ Consultant on the FMOH-UNICEF-NAFDAC Code Implementation Project in Nigeria.
*No Competing Interests.

Competing interests: No competing interests

25 January 2021
CHARLES OSAYANDE EREGIE
MEDICAL DOCTOR
Professor of Child Health and Neonatology, University of Benin and Consultant Paediatrician and Neonatologist, University of Benin Teaching Hospital, Benin City, Nigeria. Also, UNICEF-Trained BFHI Master Trainer and ICDC-Trained in Code Implementaion. Also a Technical Expert/ Consultant on FMOH-UNICEF-NAFDAC Project on Code Implementation in Nigeria
Institute of Child Health, College of Medical Sciences, University of Benin, Benin City, Nigeria.