Intended for healthcare professionals

Rapid response to:


Vaccines, convalescent plasma, and monoclonal antibodies for covid-19

BMJ 2020; 370 doi: (Published 09 July 2020) Cite this as: BMJ 2020;370:m2722

Read our latest coverage of the coronavirus pandemic

Rapid Response:

COVID-19 Pandemic, vaccines, vaccinations and antibody therapies: The paradox of making haste slowly with cautious optimism

The ‘Unprecedented Ragingly Devastating 21st Century Scourge’ continues to ‘Task and Challenge’ the ‘Global Capacity/ Preparedness’ to ‘Weather the Storm’ [1-6]! The deployed ‘Global Armoury’ for the ‘COVID-19 Pandemic’ is increasingly undermined by the ‘Rapidly Dynamically Transmuting Pandemic Specifics’ which have necessitated the ‘Deluge of COVID-19 Research Outpourings’ but which, unfortunately with STRICT ADHERENCE to ‘Best Research Standards’, are largely reported as ‘COVID-19 Research Waste’ [7-10]!! While some ‘Communications’ call for OVERLOOKING the ‘Time-tested Research Standards’ [11-14], others advocate STRICTLY UPHOLDING ‘Conventional Research Standards’ to eclipse the enlargement, and possible reduction, of extant ‘COVID-19 Infodemic’ [15,16]!! The level of ‘Politics’ polluting the ‘Science-Facts-Evidence’ of ‘COVID-19 Pandemic’/ ‘COVID-19 Research’ has the POTENTIALITY of assuming ‘Pandemic Proportions’ [17]!! Some ‘Issues’ will be disposed concerning Vaccines, Vaccinations and Antibody Therapies for ‘SARS-CoV-2’ and ‘COVID-19’.

The ‘COVID-19 Pandemic Devastations’ are due to ‘Lethality’ and ‘Transmissibility’ of ‘SARS-CoV-2’ against which ‘Global Interventions’ are directed! These reflect ‘Pathogenicity’ and ‘Immunogenicity-Antigenicity’ of the ‘Novel Coronavirus’! Some ‘Anti-COVID-19 Pharmaceuticals’ are directed against ‘SARS-CoV-2 Lethality’ to influence the ‘Clinical Outcomes’ for ‘Persons Contracting the SARS-CoV-2’ and are currently in various ‘Stages and Phases of Clinical Trials’: ‘Anti-COVID 19 Drugs, Vaccines and Antibody Therapies’!! These ‘Anti-COVID-19 Pharmaceuticals’ are expected to also influence ‘SARS-CoV-2 Transmissibility’ altering the ability of ‘Transmission’ by ‘Persons who Contract SARS-CoV-2’!! These ‘Anti-COVID-19 Pharmaceuticals’ are still largely in ‘Clinical Trials’ requiring STRICT ADHERENCE to ‘Best Research Standards’ COMPLETELY DEVOID of ‘Worrisome Politics’!! The WHO has recommended that ‘Politics’ should be ‘Quarantined’ in the ‘COVID-19 Pandemic’!!!

The ‘SARS-CoV-2 Transmissibility’ can also be altered by ‘Anti-COVID-19 Pharmaceuticals’ still largely in ‘Clinical Trials’ and ‘Anti-COVID-19 Non-Pharmaceutical Interventions (NPIs)’! The latter are the ‘Interventions that Work and still also in the Works’ and should attract proportionately more ‘Research-Development Investments’ but currently not so; ‘Interventional Inequity’ [10,18]!! The NPIs are part of the ‘COVID-19 Mitigation Methods’ [19-27]!!! This current ‘Communication’ addresses ‘Anti-COVID-19 Pharmaceuticals’ still largely in ‘Clinical Trials’ and, hence, the World MUST ‘MAKE HASTE SLOWLY’ with demonstrable ‘CAUTIOUS OPTIMISM’ kowtowing to the ‘Best Research Standards’ and AVOIDING ‘Dangerous Politics’; The ‘Uncertainties and Unknowns’ concerning the ‘Pharmaceuticals’ are legion!!! The ‘Anti-COVI-19 Drugs’ are not discussed in this ‘Communication’.

The ‘Non-Drugs Anti-COVID-19 Pharmaceuticals’ are bifid concerning their ‘Domain of Action’: ‘Active Immunity’ and ‘Passive Immunity’! For ‘Active Immunity’, several ‘Candidate Vaccines’ are in different ‘Phases of Clinical Trials’ [28,29]! Many such ‘COVID-19 Candidate Vaccines’ target the ‘Receptor Binding Domain (RBD)’ Region of the ‘Viral Spike Protein’ required for ‘Cell Invasion’ by binding to the ‘ACE 2 Receptor’ on the Human Cell Membrane [29]! There are several ‘Issues in the Works’ concerning this ‘Vaccine-Target Approach’: Do they induce ‘Neutralizing Antibodies’ sufficiently blocking the ‘ACE 2 Receptors’, ‘Antibody Production Determinants’, ‘Antibody Production Response Time’, ‘Antibody Span/ Reinfection-Reactivation’, ‘Antibody Presence/ Level’ equivalent to ‘Immunity/ Protection’, ‘T Cell Role’ etc? The ‘Implications’ of ‘SARS-CoV-2 Genetic-Genomic Diversity’/ ‘Viral Recombination Capacity’ need exploration re: ‘Vaccine-Target Approach’ [30]! The ‘RBD of the Spike Protein’ is relatively conserved with some ‘Mutations’ but very ‘Substantial Mutations’ possibly affect ‘Vaccine Effectiveness’ [31-33]!! ‘Lessons from Previous Epidemics-Pandemics’ are instructive re: sustained ‘Interest and Impetus’ for ‘Candidate Vaccines Research Enterprise’ with waning of the ‘Pandemic Numbers’ [34]!! From previous experience, ‘Big Company Investments’ dwindle with ‘Victory over the Pandemic’ with abandonment of ‘Further Candidate Vaccines Research-Production Commitments’!! Additionally, the efforts to produce ‘Coronavirus Vaccines’ against SARS and MERS were unsuccessful [35] and ‘Vaccines against Other RNA Viruses’ were also not successful with some even causing ‘Disease Exacerbations’ from ‘Antibody-Dependent Enhancement (ADE)’ [36]!! The ‘SARS-CoV-2 Genetic-Genomic Diversity’ begets ‘Vaccine Production Precursor Diversity’: Whole Virus, Viral Genetic Sequence, Viral Proteins etc!!!

Concerning ‘Anti-COVID-19 Pharmaceuticals’ and ‘Passive Immunity’, there are ‘Bifid Possibilities’: ‘Convalescent Plasma Antibodies in Clinical Trials’ [37] and ‘Monoclonal Antibodies in Clinical Trials’ [38,39]! The success with ‘Convalescent Blood’ for ‘Ebola Virus Disease’ in 2014 is instructive/ ‘Driving Impetus’ for the ‘Convalescent Plasma Trials’ [40]!! Still ‘Unresolved Issues’ with ‘Convalescent Plasma Antibodies’: ‘Many Antibodies’ with some ‘Non-Neutralizing’, ‘Non-Viral Spike Protein Targeted’, ‘Optimal Administration Time’ and possible ‘Antibody-Dependent Enhancement (ADE)’/ ‘Worsening Disease’; ‘T Cells from Recovered Patients’? For ‘Monoclonal Antibodies’, again, ‘Bifid Approach’: ‘Humanized Monoclonal Antibodies’ from ‘B Cells from Recovered COVID-19 Patients’ and ‘Laboratory-based Genetically Engineered Monoclonal Antibodies’ [41,42]!! ‘Monoclonal Antibodies’ are beneficial: ‘Single Neutralizing Antibodies’ more specific to ‘Target Sites’ compared with ‘Convalescent Plasma’! The ‘COVID-19’ induces ‘Immune Dysregulation’ with very ‘High Antibody Levels-Immune Hyperactivity’ in Severe Disease [43,44] making ‘Optimal Time for Antibody Administration’ an ‘Unresolved Issue’ re: Possible ‘Antibody-Dependent Enhancement’! This applies to ‘Convalescent Plasma’ and ‘Monoclonal Antibodies’!! Outstanding ‘Issues’: ‘Cross-Neutralizations’, ‘Clonal Expansions’, ‘Somatic Hypermutation (SHM)’ etc [45,46]!!!

Another ‘Issue in the Works’ is ‘Vaccination’ even after ‘Successful Candidate Vaccines Research’! The ‘Issues’: Mass Production, Supply Chain Variables, Distribution and ‘Inverse Equity Hypothesis’ with worsening ‘Vaccines Access-Health Inequalities’; Those most in need possibly are the least to receive the critically needed ‘Interventions’!! Another ‘Issue for the Works’’: ‘VIP Triad’ even when there is ‘Vaccination’! Does ‘Vaccination’ necessarily result in ‘Immunization’ and does this necessarily result in ‘Protection’? For example, the ‘Elderly Population’ who experience ’More Severe COVID-19’ are reported with poor ‘Immune Response’ to ‘COVID-19 Candidate Vaccines’ from ‘Immune Senescence’ [33]!! Would this necessitate ‘Frequent/ Multiple Vaccinations’ or ‘Vaccine Adjuvants’? An evolving ‘Unimaginable Issue’ is ‘Compromised Public Trust’ on the ‘COVID-19 Candidate Vaccines Trials’ because of the ‘Frightening Reported Progress Speed’ which is conjectured will most likely breach ‘Conventional Research Standards and Integrity’!! The ‘Public Acceptance of Vaccination’ is now seriously questioned!! This will likely affect Vaccination Coverege, Population Antibody Levels and Herd Immunity!!! The dangerous influence of ‘Politics and Political Pressure’ over ‘Science, Facts and Evidence’ concerning ‘COVID-19 Pandemic’ is, once again, brought to the fore [17]!!

This ‘Communication’ is a ‘Contribution’ to the extant ‘Anti-COVID-19 Pharmaceuticals Conversations’ as they concern ‘Candidate Vaccines’, ‘Vaccinations’ and ‘Antibody Therapies’ (‘Convalescent Plasma’ and ‘Monoclonal Antibodies’) with a ‘Clarion Call’ to ‘MAKE HASTE SLOWLY’ with ‘CAUTIOUS OPTIMISM’!

1. Godlee F. COVID-19: Weathering the storm. BMJ 2020; 368:m1199 of 26th March 2020
2. Eregie C.O. COVID-19 Pandemic: Still on the difficult unresolved increasing challenges in weathering the storm. of 2nd April 2020
3. Eregie C.O. COVID-19 Pandemic: Further perspectives on the difficult unresolved increasing challenges in weathering the storm. of 5th April 2020 Godlee Weather
4. Kickbusch I, Leung GM, Bhutta ZA, Matsoso MP, Ihekweazu C, Abbasi K. Covid-19: how a virus is turning the world upside down. BMJ 2020; 369:m1336 of 3rd April 2020
5. Appleby J. Tackling covid-19: are the costs worth the benefits? BMJ 2020; 369:m1496
6. Eregie C.O. Tackling COVID-19 Pandemic: all relevant impactful observables should be captured in the cost-benefit balance. of 7th May 2020
7. Waste Clinical History of changes for study. NCT04280705, 1 May 2020.
8. 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.
9. Glasziou PP, Sanders S, Hoffmann T. Waste in covid-19 research. BMJ 2020; 369:m1847
10. Eregie CO. COVID-19 Pandemic: The multifaceted picture of compromised COVID-19 research and the COVID Phenomenon’. of 10th June 2020
11. 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
12. Conroy G. Preprints boost article citations and mentions. Nature Index 2019 Jul 9.
13. Fry NK, Marshall H, Mellins-Cohen T. In praise of preprints. Microb Genom 2019; 5:e000259. Doi: 10.1099/mgen.0.000259. pmid:30938670
14. Karmakar S, Dhar R, Jee B. Covid-19: research methods must be flexible in a crisis. BMJ 2020; 370:m2668
15. Eregie CO. COVID-19 Pandemic, the quest for urgent information and solutions and the paradox: making haste slowly to avoid ‘COVID-19 Research Waste’. of 17th July 2020
16. 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’. of 21st July 2020
17. Eregie C.O. COVID-19 Pandemic, ‘COVID Phenomenon’ and the politics of the science, facts, research evidence and ‘evidence-based medicine (EBM): the imperative for rekindling the ‘multiparameter-based medicine (MBM) in the 21st Century. of 17th April 2020
18. Eregie C.O. Obesity as a Public Health Emergency: A look at the ‘Pre-FOAD Hypothesis’ as a Panacea for the ‘Interventional Inequity. of 4th October 2019
19. Melnick ER. Should governments continue lockdown to slow the spread of covid-19? BMJ 2020; 369:m1924
20. Godlee F. Covid-19: It’s too soon to lift lockdown. BMJ 2020; 369:m2202
21. Eregie CO. COVID-19 Pandemic Interventions: Lockdown is not lockout; avoid interventional precocity with easing lockdowns. of 14th June 2020
22. Middleton JD, Lopes H. Face masks in the covid-19 crisis: caveats, limits and priorities. BMJ 2020; 369:m2030
23. Wetsman N. CDC recommends people wear cloth masks to block the spread of COVID-19. The Verge of 3rd April 2020
24. Eregie C.O. COVID-19 Pandemic and face mask use: Limitless matters for extant conversation. of 11th June 2020
25. Schroter RC. Social distancing for covid-19: is 2 meters far enough? BMJ 2020; 369:m2010
26. Hwang J, Lee K. Determination of outdoor tobacco smoke exposure by distance from a smoking source. Nicotine Tob Res 2014; 16:478-84
27. Eregie CO. COVID-19 and social distancing: more work in the works to be there. of 12th June 2020
28. Caddy S. Developing a vaccine for covid-19. BMJ 2020; 369:m1790
29. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest 2020; 130:1545-
30. Shen Z, Xiao Y, Kang L et al. Genomic diversity of SARS-CoV-2 in Coronavirus Disease 2019 patients. Clin Inf Dis. of 9th March 2020
31. 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
32. 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
33. Swell HF, Agius RM, Kemdrick D, Stewart M. Vaccines, convalescent plasma and monoclonal antibodies for Covid-19. BMJ 2020; 370:m2722
34. COVID-1: Lessons and Recommendations. of 12th March 2020
35. Padron-Regalado E. Vaccines for SARS-CoV-2: lessons from other coronavirus strains. Infect Dis Ther 2020:1-20.doi:10.1007/s40121-020-00300-x. pmid:32328406
36. Graham BS. Rapid COVID-19 vaccine development. Science 2020; 368:945-6. Doi:10.1126/science.abb8923 pmid:32385100
37. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020; 181:281-292. e6. doi:10.1016/j.cell.2020.02.058 pmid:32155444
38. Liu A. Regeneron scales up manufacturing, eyes human tests of COVID-19 antibody cocktail in June. Fierce Pharma. 5 May 2020.
39. Lilly begins world’s first study of potential covid-19 antibody treatment in humans. Press release., 1 June 2020
40. Sahr F, Ansumana R, Massaquoi TA et al. Evaluation of convalescent whole blood for treating Ebola virus disease in Freetown, Sierra Leone. J Infect 2017; 74:302-9
41. Alansari K, Toaimah FH, Almatar DH, El Tatawy LA, Davidson BL, Qusad MIM. Monoclonal antibody treatment of RSV bronchiolitis in young infants: a randomized trial. Pediatrics 2019; 143:e20182308. doi:10.1542/peds.20182308 pmid:30760509
42. Biegel JH. Polyclonal and monoclonal antibodies for treatment of influenza. Curr Opin Infect Dis 2018; 31:527-34
43. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med 2020; 8:e46-7
44. Hou H, Wang T, Zhang B et al. Detection of IgM and IgG antibodies in patients with coronavirus disease 2019. Clin Transl Immunology 2020; 9:e01136
45. 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
46. Eregie CO. Covid-19 Pandemic, SARS-CoV-2 antibodies and testing: Still searching for more facts. of 16th July 2020

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 July 2020
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.