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

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2722 (Published 09 July 2020) Cite this as: BMJ 2020;370:m2722

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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’!

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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
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.