Intended for healthcare professionals

Rapid response to:

News News Analysis

Covid-19 vaccination: What’s the evidence for extending the dosing interval?

BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n18 (Published 06 January 2021) Cite this as: BMJ 2021;372:n18

Read our latest coverage of the coronavirus outbreak

Opinion

Covid-19 vaccines: to delay or not to delay second doses

Opinion

How do you take your vaccine—one lump or two?

Rapid Response:

COVID-19 Pandemic, beyond the ‘Vaccines Marathon Finish Line’ and ‘Post-Vaccine Approval Programmatic Haze’: The evolving ‘2nd Dose Uncertainties’; still more unfolding ‘Matters in the Work’

Dear Editor

The ‘Global Fight’ against the ‘COVID-19 Pandemic’ is ‘Programmatically Signposted’ with the ‘Approved COVID-19 Vaccine Interventional Milestones’! The clear ‘Programmatic Difference’ between ‘Vaccines’ and ‘Vaccinations’ is increasingly a ‘Yawning Interventional Difficulty’!! The ‘Vaccines-Vaccinations Programmatic Metamorphosis’ is replete with ‘Poked Holes’ ascribable to the evolving ‘2nd Dose Uncertainties’[1-11]!! With further unfolding ‘Programmatic Difficulties’ quaking the ‘Vaccines-Vaccinations Metamorphosis’, this ‘Communication’ disposes more emerging ‘2nd Dose Uncertainties’!!!

Additional emerging ‘2nd Dose Uncertainties’ are disposed vide infra:

1. ‘2nd Dose and Booster’: Emerging ‘Conversation’ now entertains the possibility of ‘Booster Doses’ after the ‘2nd Dose’: Not ‘Clinical Trials Data’-based but occasioned by ‘Programmatic Difficulties’ and ‘COVID-19 Interventional Distortions’; Troubled ‘Global Fight’ against the ‘COVID-19 Pandemic’! Evolving ‘Contemporary Conversation’ suggests ‘Booster Doses’ are heading towards the ‘Vaccination Programme Front-Burner’!! The ‘Booster Doses’, possibly not initially part of the ‘Vaccination Programme’, will soon attain another ‘Locus’ for ‘Contemporary Vaccination Conversation’!!!

2. ‘2nd Dose and Signed Informed Consent Form’: People are made to sign the ‘Informed Consent Form’ ostensibly predicated on ascertained ‘Understanding and Acceptance’ of the ‘Undergirding Terms’ for ‘Receiving the Vaccine’ including: Number of Doses, Interval between Doses among others[12,13]!! There are implications for the altered ‘Terms’ re: ‘Informed Consent Form’-‘Informed Consent’ including the ‘2nd Dose Specifics’!!!

3. ‘2nd Dose and Indemnity’: There is ‘Indemnity’ for Manufacturers, Distributors and Administrators/ Vaccinators in case of ‘Adverse Reactions’ arising from the ‘Vaccine’ provided the ‘Anticipated Authorization Parameters’ are ‘Intact/ Unaltered’[12-14]!!

4. ‘2nd Dose and Other Legal Issues’: A ‘Contract’ is an ‘Actionable Agreement’! The ‘Vaccines Availability’ is one issue and ‘Vaccination’ is yet another denominated in ‘Vaccines in the Arms’ according to ‘Actionable Agreement’ with the ‘Vaccine Recipients’. Therefore, any breach is a basis for ‘Legal Tango’!

5. ‘2nd Dose and Emergency Use Authorization Basis’: The rush to the ‘Vaccines Marathon Finish Line’ took cognizance of ‘Clearly Distilled Conditions’ predicated on verifiably available ‘Transparent Clinical Trials Data’ situate with ‘Best Practices’-‘Robust Research Governance Principles’. These ‘Conditions’ are reflected in the ‘Anticipated Authorization Parameters’ which enable the ‘Vaccines’ to be ‘Administered into Arms’ (Vaccinations)! Adherence to the strict ‘Anticipated Authorization Parameters’ is sacrosanct and must be so incontrovertibly disposed!!

6. ‘2nd Dose and Epidemic Curve Realities’: It is rather bothersome that ‘Authorities/ Experts’ certainly knowledgeable about the ‘Terms’ of the ‘Vaccine Administration’ will be kowtowing to the ‘Pressures’ due to the ‘COVID-19 Epidemic Curve Realities’ to justify/ rationalize ‘1st Vaccine Dose’ ahead of ‘2nd Dose’ with the inherent dangers and potentiality of ‘Vaccine Inefficacy/ Ineffectiveness’ and ‘Vaccine Resistance’!!

7. ‘2nd Dose and Health Services Strain’: Here is another tenuous stance for prioritizing ‘1st Dose’ ahead of the ‘Scheduled 2nd Dose’ believing that with more persons receiving the ‘1st Dose’, there will be less ‘Infections’ and less ‘Hospitalizations’ with ‘Reduced Strain’ on the ‘Stretched Resources’ of the Health Services; ‘Complete Vaccination’ is determinant!!

8. ‘2nd Dose and Contraindications’: Are there clearly stated ‘Contraindications’ for the ‘2nd Dose’ and what should be done to assure ‘Complete Vaccination’ and ‘Protection’ while minimizing possible ‘Health Hazards’ and ‘Vaccine Resistance’?

9. ‘2nd Dose Delays, Vulnerable Groups and Consequences’: Previous Report indicates that a particular ‘Approved Vaccine’ is more effective in the 18-55 years bracket and less so in those over 55 years[14]! Another Report indicates ‘Immune Response’ from ‘1st Dose’ is not sustained beyond 42 days[15]!! What then is the fate of the more vulnerable ‘Persons over 55 years’ and are beyond 42 days waiting for rescheduled ‘2nd Dose’ to end of 12 weeks[2]?

10. ‘2nd Dose Delays, Interval Infection and Burden-Cost’: In the event of an ‘Interval Infection’ while waiting for the rescheduled ‘2nd Dose’, who is responsible for the ‘Burden’ and ‘Cost’ of care and any liabilities for the breach of the ‘Anticipated Authorization Parameters’ and the ‘Signed Informed Consent Form’?

11. ‘2nd Dose and Dose Reduction’: With the ‘Vaccine Production-Supply Chain Logistics Difficulties’, there are ‘Projected Vaccine Availability Distortions’! Reductions in ‘Vaccine Doses’ are being considered and may affect both the ‘1st Doses’ and the ‘2nd Doses’[16]!!

12. ‘2nd Dose and Shipment Supplies in Reserve’: Indeed, there are strategies to support ‘Front-Loading’ for the ‘1st Dose’ against the ‘Halving of Shipments in Reserves’ for the ‘2nd Dose’ with implications[17]!

13. ‘2nd Dose, ‘Vaccination Coverage’ and ‘Complete Vaccination’: The ‘Science of Vaccinology’ and the ‘VIP Triad/ Concept’ are important for this discourse. ‘Vaccination’ begets ‘Immunization’ and ‘Immunization’ results in ‘Protection’[18]!! Of course, there are ‘Confounding Variables’ which assure the ‘VIP Triad Transformation’ but the ‘Vaccination’ that is of ‘Determinant Impact/ Importance’ is ‘Complete Vaccination’ which requires the ‘2nd Dose’ as a Sine Qua Non! The mass spreading of the ‘1st Dose’ impacts on ‘Vaccination Coverage’ but it is the ‘2nd Dose’ that assures ‘Complete Vaccination’!!!

14. ‘2nd Dose, Vaccine Production-Supply Chain Logistics and International Politics-Transparency’: The WHO recommends that ‘National Unity’ and ‘Global Solidarity’ are necessary for the successful ‘Global Fight’ against the ‘COVID-19 Pandemic’! With ‘Vaccine Availability Difficulties’, the envisioned recommended ‘Global Solidarity’ is being fractured! The European Union is raising concerns and alert regarding the ‘Agreements’ with ‘Vaccine Manufacturers’ seemingly being disrupted by some interested Countries as Parties!! Germany recently indicated its intention not to delay the ‘2nd Dose’ suggesting no ‘Global Solidarity’ on the ‘Issue’[19]!!

15. ‘2nd Dose and Inverse Equity Hypothesis-‘Vaccine Nationalism’’: The High-Income Countries are ‘Bulk Buying and Blocking-Trapping Vaccines’ away from the ‘Reach’ of the Low-Income Countries! The Low-Income Countries in need are not likely to benefit timeously from the ‘Approved Vaccines’ amplifying the ‘Inverse Equity Hypothesis’. Within Countries, ‘Inequitable Distribution’ is a ‘Huge Issue’!! The ‘Vaccine Nationalism’ of this ‘Vaccine Distribution Inequity’ to protect ‘Country Nationals’ is different from the previously reported ‘Vaccine Nationalism’ of some Countries ‘Crossing’ the ‘Vaccines Marathon Finish Line’ before getting to the ‘Finish Line’: ‘Approving’ and ‘Using’ the ‘Candidate Vaccines’ while still in the ‘Phase III Clinical Trials’[20]!!

The ‘2nd Dose Issue’ is increasingly quaking the ‘COVID-19 Vaccination Programmes’! It was recently suggested: ‘Vaccine Dose Delayed is Vaccine Dose Never Received’!! This ‘Communication’ is a further ventilation of this extant ‘COVID-19 Vaccination Programmatic Difficulty’ re: ‘2nd Dose Uncertainties’!!

REFERENCES
1. NHS. Letter to chief executive of all NHS trusts and foundation trusts. 30 Dec 2020. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/... -December-2020.pdf.
2. Department for Health and Social Care. Letter to the profession from the UK chief medical officers regarding the UK covid-19 vaccination programmes. 31 Dec 2020. https://www.gov.uk/government/publications/letter-to-the-profession-from....
3. Voysey M, Clemens SAC, Mahdi SA et al. Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa and the UK. Lancet 2020; S0140-6736(20)32661-1.doi:10.1016/S0140-6736(20)32661-1.pmid:33306989
4. EU says interval between Pfizer vaccine doses should be respected. Reuters. 4 Jan 2021. https://www.reuters.com/article/us-health-coronavirus-ema-pfizer-idUSKBN...
5. Mahase E. Covid-19: Order to reschedule and delay second vaccine dose is ‘totally unfair’ says BMA. BMJ2020; 371:m4978
6. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. 4 Jan 2021. https://www.gov.uk/government/publications/regulatory-approval-of-covid-....
7. Robertson J et al. Covid-19 vaccines: to delay or not to delay second doses. BMJ Opinion. 5 Jan 2021. https://blogs.bmj.com/bmj/2021/01/05/covid-19-vaccines-to-delay-or-not-t....
8. Mahase E. Covid-19: Vaccine brands can be mixed in ‘extremely rare occasions’ says Public Health England. BMJ 2021; 372:n12
9. Branswell H. Britain takes a gamble with Covid-19 vaccines, upping the stakes for the rest of us. Stat 2021. https://www.statnews.com/2021/01/04/britain-takes-a-gamble-with-covid-19....
10. British Society for Immunology. Statement on covid-19 vaccine dosing schedules. https://www.immunology.org/policy-and--public-affairs/briefing-and-posit....
11. Eregie CO. COVID-19 Pandemic, beyond the ‘Vaccines Marathon Finish Line’ and ‘Post-Vaccine Approval Programmatic Haze’: The evolving ‘2nd Dose Uncertainties’. https://www.bmj.com/content/372/bmj.n18/rr-12 of 24th January 2021
12. Public Health England. Green Book. Chapter 14a: Covid-19-SARS-CoV-2. Dec 2020.https://assets.publishing.service.gov.uk/government/uploads/system/uploa...
13. lacobucci G, Mahase E. Covid-19 Vaccination: What is the evidence for extending the dosing interval? BMJ; 3021:n18
14. Public Assessment Report-Gov.uk. https://www.assets.publishing.service-gov.uk/
15. EU says interval between Pfizer vaccine doses should be respected. Reuters. 4 Jan 2021. https://www.reuters.com/article/us-health-coronavirus-ema-pfizer-idUSKBN...
16. Ehley B. Feds may cut moderna doses in half so more people get shots. Warp Speed Adviser says. https://www.politico.com/news/2021/01/03/moderna-vaccine-doses-warp-speed
17. Tufekci Z. The Mutated Virus is a Ticking Time Bomb. https://www.theatlantic.com/science/archive/2020/12/virus-mutation-catas...
18. Swell HF, Agius RM, Kemdrick D, Stewart M. Vaccines, convalescent plasma and monoclonal antibodies for Covid-19. BMJ 2020; 370:m2722
19. Reuters Staff. Germany says does not intend to delay second COVID-19 vaccine shot. Thhps://www.reuters.com/article/us-health-coronavirus-germany-spahn/germany
20. 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.

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

27 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.