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­­Speaking truth to power

BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n24 (Published 07 January 2021) Cite this as: BMJ 2021;372:n24

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COVID-19 Pandemic and COVID-19 Vaccinations: Beyond the ‘Vaccines Marathon Finish Line’; The Unfolding ‘Works in The Work’

The BMJ is appreciated for its ‘Institutional Policy’: Recognizing ‘Personalities’ with well-formed Human Conscience, Knowledge and Courage who ‘Speak Truth to Power’[1]. Beyond listing some previous BMJ Prize Winners, and the current, several ‘Issues’ relating to ‘COVID-19 Vaccines’-‘Vaccinations’ are ventilated. These ‘Issues’, similarly exposed in previous ‘Communications’, critically distil the clear ‘Programmatic Difference’ between ‘Vaccines’ and ‘Vaccinations’ re: ‘Matters’ disposing ‘Before’ and ‘Beyond’ the ‘Vaccines Marathon Finish Line’[2-7]! This ‘Communication’ amplifies some ‘Tantalizing Matters’: ‘Beyond’ the ‘Vaccines Marathon Finish Line’!

A ‘Huge Challenge’ with ‘Vaccine Production’ exists. There was ‘Mass Vaccine Production’ with ‘Anticipated Approvals (‘FINISH LINE’)’ BUT there is now a ‘Landmark Difficulty’: No ‘Reserved Vaccines’ for the ‘Second Doses’!! While some appropriately received their ‘Recommended Second Doses’, several others have no hope for theirs and, indeed, their ‘First Doses’!!!

The ‘Vaccine Transportation’ is ‘Multi-dimensional’: Warehouse-Airports/ Trucks, Airports-Airports/ Aircrafts, Airports-District Warehouses/ Trucks and District Warehouses-Health Facilities/ Vehicles! Reported ‘Difficulties’ exist with ‘Vaccine Transportation’ through ALL the ‘Multi-dimensional Levels’!!

The ‘Vaccine Distribution’ is another ‘Issue’ being grappled with ‘Beyond the Finish Line’. There is reported ‘Inverse Equity Hypothesis-related Vaccine Distribution’ with the POTENTIALITY of worsening ‘Social Disparities’-‘Health Inequalities’[3,7]. There appears to be ‘Difficulty’ assuring those ‘Most in Need’ have the vaccines ‘Timeously Delivered as Priority’! While millions of ‘Vaccine Doses’ have been delivered to the High-Income Countries, most Low-Income Countries are yet to have theirs! There should be ‘Global Vaccine Equity’[8,9]!!

Another ‘Issue’ is ‘Vaccine Delivery-Vaccine Administration Dissociation’. With millions of vaccines delivered to ‘Desired Designated Places’, significantly much less proportions have been successfully administered to the populace! A bothersome proportion of the populace is yet to receive ‘Vaccines in the Arms’! The ‘Confounding Contributors’ to this ‘Dissociation’ include, among others: Inadequate Personnel, Inadequate ‘Vaccination Sites’, Inequitable Vaccines Distribution, Lack of Uniform National Vaccination Plan and ‘Vaccine Hesitancy’!

‘Vaccine Hesitancy’ is another ‘Beyond the Finish Line Issue’. This mirrors the ‘Populace Demand’ for the ‘Approved Vaccines’. The ‘Confounding Contributors’, among others, include: The Vaccines Development Speed, Questionable Strict Adherence to the Science of Vaccinology, Questionable Application of Strict Research Principles in the Clinical Trials Phases and the Role of Politics undermining Science as previously disposed [3,7, 10-20].

‘Vaccines’ do NOT control ‘Pandemics’ but ‘Vaccinations’ may and the ‘Difference’ and ‘Determinants’ are denominated in ‘Vaccines Uptake’[3,7,21]! The ‘Vaccines Uptake Determinants’ are protean and ultimately reflect ‘Vaccine Hesitancy’. The ‘Vaccine Efficacy-Safety-Trust’ must never be taken for granted or eroded by ‘POLITICS’ undermining ‘SCIENCE’ of ‘Vaccines-Vaccinations-Protection’!!

Yet another compelling ‘Issue’, as a ‘Programmatic Thrust’, is ‘Vaccine Efficacy’. The ‘Vaccine Efficacy Determinants’ were explored in previous ‘Communications’: Vaccine Production Precursor Diversity/ Specific Type Used, Type of Immune Response/ Profile, Antibodies Produced/ Determinant Specifics, Immunity Duration and Reactivation/ Reinfection among others[22-28]! This rekindles the implications of the ‘VIP Triad/ Concept’: Vaccination-Immunization-Protection’!! The ‘Issue’ of ‘Vaccine Safety’ also comes to the fore. ‘Safety Issues’ appear not to have been critically reported antedating the ‘Vaccine Marathon Finish Line’!! Subsequently, ‘Adverse Reactions’ were reported with ‘Approved Vaccines’!!!

‘Vaccine Trial Population Diversity Issue’ impacting ‘Beyond the Finish Line’ is also exciting further deserving attention. The ‘Vaccines’ from ‘Candidate Vaccines’ in the ‘Phase III Clinical Trials’ were not exposed to ALL possible ‘Population Diversity Spectrum’[29] with implications for ‘Vaccines Administration’-‘Population Coverage’-‘Herd Immunity’-‘COVID-19 Pandemic Control’!! A raging ‘Case-in-Point’ is the ‘Conflicting and Confusing Recommendation’ concerning ‘Vaccine Administration’ to ‘Pregnant Women and Breastfeeding Mothers’[30]!

The emergence of ‘SARS-CoV-2 Variants’ was only a matter of time and a short time indeed! No sooner had ‘Approved Vaccines’ been ‘Transported-Delivered-Administered’ than various ‘SARS-CoV-2 Variants’ were reported from different parts of the world: United Kingdom, United States of America, South Africa, Brazil and still counting and reporting!! The ‘SARS-CoV-2’ distinctly has ‘Viral Genetic-Genomic Diversity’-‘Viral Recombination Capacity’[31]! These ‘SARS-CoV-2 Variants’ have more ‘Transmissibility’ with implications for ‘Daily New Infections’, ‘Daily Hospitalizations’ and possibly ‘Daily Deaths’ which ‘Reshape’ the ‘COVID-19 Epidemic Curves’ in the affected areas!! A particular ‘SARS-CoV-2 Variant’ is reported to have several ‘Mutant Strains’!! The discourse on ‘Vaccine Efficacy’ with respect to the ‘SARS-CoV-2 Variants’ is an evolving matter with protean possibilities[32-34]!!

The ‘SARS-CoV-2 Variants’ have also introduced a ‘Huge Issue’ into ‘Beyond the Finish Line Possibilities’: Reported worrisome emergence and existence of ‘Vaccine-resistant Virus Varieties’! This has implications for ‘Vaccine Efficacy’ and the alteration of the ‘COVID-19 Epidemic Curves’ in the affected locales.

The ‘COVID-19 Pharmaceuticals Catastrophe’ related largely to ‘Before the Vaccines Marathon Finish Line’[7] but it definitely impacts hugely on the unfolding ’Post-Vaccines Approval Realities’! This is the imperative of upholding the ‘Best Practices’-‘Research Governance Principles’ in ‘Vaccines Development’: The ‘Initial Investigations’ and the ‘Candidate Vaccines through the 3-Phase Clinical Trials’!!

The ‘Vaccines Rollout Plan’ MUST align with the ‘WHO Counsel’ for winning the ‘Global War’ against the ‘COVID-19 Pandemic’: ‘National Unity’ and ‘International Solidarity’! The ‘Country Rollout Plan’ MUST regard the ‘End-Point’ as ‘Vaccines Administered into the Arms’ and not merely ‘Vaccines Delivered to Places’! There must be verifiably available ‘Coordinated Strategies’ for assuring that ‘Vaccines’ approximate ‘Vaccinations’ for the Populace for ‘Vaccines’ to become ‘Solutions’ to the ‘COVID-19 Pandemic’!!

Other ‘Issues’ exist but not ventilated herewith: ‘Vaccine Temperatures Maintenance’, ‘Vaccine Dosage Wastages’, ‘Vaccine Reconstitution Difficulties’, ‘Vaccine ‘Open and Must Use’ Prescription’, ‘Vaccine Dosage Schedules’ etc. As feasible, these ‘Determinant Issues’ may be further critically explored and comprehensively exposed!

The ‘Non-Pharmaceutical Interventions (NPIs)’, the ‘Interventions that Work’ in the ‘COVID-19 Pandemic Control’, MUST continue to be implemented in a ‘Horizontal Programme’ in complementarity with ‘Vaccines Intervention’! The ‘Vaccines Production-Distribution-Availability-Administration’ should not be implemented in ‘Vertical Programmatic Alignment’ with the NPIs!! Too many ‘Confounding Determinants’ affect ‘Vaccine Efficacy’ while ONLY ‘Strict Compliance’ is largely required for effectiveness of the NPIs in the ‘COVID-19 Pandemic Control’!!

This ‘Communication’ is a modest ‘Contribution’ in appreciation of the ‘BMJ Institutional Policy’ to continue encouraging, recognizing and rewarding ‘Speaking Truth to Power’! It also further ventilates the ‘Difficult Realities’ which dot the terrain ‘Beyond the Vaccines Marathon Finish Line’. There are certainly ‘More Works in the Work’ to transform ‘Vaccines’ to ‘Vaccinations’ and ‘Vaccines’ to ‘Solutions’ in the ‘Global Fight’ against the ‘COVID-19 Pandemic’.

REFERENCES
1. Godlee F. Speaking truth to power. BMJ 2021; 372:n24
2. Graham BS. Rapid COVID-19 vaccine development. Science 2020; 368:945-6. Doi:10.1126/science.abb8923 pmid:32385100
3. Eregie CO. COVID-19 Pandemic, vaccines, vaccinations and antibody therapies: The paradox of making haste slowly with cautious optimism. https://www.bmj.com/content/370/bmj.m2722/rr-2 of 27th July 2020
4. 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
5. Mahase E. Covid-19: Where are we on immunity and vaccines? BMJ 2020;370:m3096
6. 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
7. Eregie CO. COVID-19 Pandemic and compromise of science and standards: Still on ‘COVID-19 Pharmaceutical catastrophe’; before and beyond the ‘Vaccines Marathon Finish Line’. https://www.bmj.com/content/370/bmj.m3260/rr-6 of 8th October 2020
8. Wang W, Wu Q, Yang J et al. Global, regional and national estimates of target population sizes for covid-19 vaccination: descriptive study. BMJ 2020; 371:m4704
9. Schwartz JL. Equitable global access to coronavirus disease 2019 vaccines. BMJ 2020; 371:4735
10. Bastos ML, Tavaziva G, Abidi SK et al. Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ 2020; 370:m2516
11. Folegatti PM, Ewer KJ, Aley PK et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-cOv-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial. Lancet 2020; S0140-6736(20)31604-4.
12. Mahase E. Covid-19: Where are we on immunity and vaccines? BMJ 2020;370:m3096
13. Altmann D. Finding the best covid-19 vaccine should not be a race: 14th August 2020. https://blogs.bmj.com/bmj/2020/08/14/finding -the-best-covid-19-vaccine-should-not-be-a-race.
14. Torreele E. The rush to create a Covid-19 vaccine may do more harm than good. BMJ 2020; 370:m3209
15. Nassisi M, Audo I, Zeitz C et al. Impact of the COVID-19 lockdown on basic science research in ophthalomology: the experience of a highly specialized research facility in France. Eye (Lond) 2020; 34:1187-8
16. Conroy G. Preprints boost article citations and mentions. Nature Index 2019 Jul 9. https://www.natureindex.com/news-blog/preprints-boost-article-citations-...
17. Fry NK, Marshall H, Mellins-Cohen T. In praise of preprints. Microb Genom 2019; 5:e000259. Doi: 10.1099/mgen.0.000259. pmid:30938670
18. Karmakar S, Dhar R, Jee B. Covid-19: research methods must be flexible in a crisis. BMJ 2020; 370:m2668
19. Eregie CO. COVID-19 Pandemic, the quest for urgent information and solutions and the paradox: making haste slowly to avoid ‘COVID-19 Research Waste’. https://www.bmj.com/content/370/bmj.m2668/rr of 17th July 2020
20. Eregie CO. COVID-19 Pandemic, the quest for urgent information and solutions and the paradox: making haste slowly to avoid ‘COVID-19 Research Waste’; time for strategic ‘COVID-19 Research Retreat for a Decad’. https://www.bmj.com/content/370/bmj.m2668/rr-0 of 21st July 2020
21. Salisbury H. Helen Salisbury: Don’t squander patients’ trust in the vaccine rollout. BMJ 2021; 372:n3
22. Zhu N, Zhang D, Wang W et al. China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020; 382:727-33
23. 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
24. 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
25. Duong YT, Wright CG, Justman J. Antibody testing for coronavirus disease 2019: not ready for prime time. BMJ 2020; 370:m2655
26. 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
27. 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
28. 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
29. Doshi P. Pfizer and Moderna’s ‘95% effective’ vaccines-we need more details and the raw data. BMJ Opinion. 4 Jan 2021
30. Hare H, Womersley K. Why were breastfeeding women in the UK denied the covid-19 vaccine? BMJ 2021; 372:n4
31. Shen Z, Xiao Y, Kang L et al. Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients. Clin Inf Dis. https://doi.org/10.1093/cid/ciaa203 of 9th March 2020
32. Li X, Giorgi EE, Marichann MH et al. Emergence of SARS-CoV-2 through recombination and strong purifying selection. BioRxiv 2020.03.20.000885 (Preprint)2020.doi:10.1126/sciadv.abb9153.pmid:32511348
33. Koyama T, Weeraratne D, Snowdon JL, Parida L. Emergence of drift variants that may affect covid-19 vaccine development and antibody treatment. Pathogens 2020; 9:E324. Doi:10.3390/pathogens9050324 pmid:32357545
34. Swell HF, Agius RM, Kemdrick D, Stewart M. Vaccines, convalescent plasma and monoclonal antibodies for Covid-19. BMJ 2020; 370:m2722

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

20 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.