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The constant thread running through several rapidly evolving ‘COVID-19 Pandemic Conversations’ is the incontrovertible fact of the ‘Unprecedented Rapidly Dynamically Transmuting Specifics’ concerning the ‘Coronavirus (SARS-CoV-2)’ and the ‘Coronavirus Disease 2019 (COVID-19)’! By the day, it increasingly becomes clearer that what is yet ‘Unknown and Uncertain’ about the ‘COVID-19 Pandemic’ increasingly outpaces and dims what is ‘Known and Certain’ because of the rapidly changing and emerging ‘Pandemic Information’!! Since ‘Nature abhors Vacuum’, the ‘Unprecedented Information Gaps’ are rapidly eclipsed by ‘Unreliable Unscientific Unsubstantiated Body of Information’ now recognized as the ‘COVID-19 Infodemic’!! The World is increasingly stimulated to gear up for the ‘Huge Stressful Intellectual and Programmatic Work’ to rise to this ‘Unacceptable Public Health Challenge’ by effecting ‘Rapidly Emerging Information Outpourings’ from several ‘Enterprises’ including ‘COVID-19 Research’!!! This ‘Communication’ focuses specifically on the ‘COVID-19 Pandemic’ as it relates to ‘SARS-CoV-2’ and the investigated ‘Antibodies’.
The ‘COVID-19 Research’ on the ‘SARS-CoV-2 Antibodies’ have become part of the evolving ‘Public Health Challenge’ in this ‘Pandemic Era’! There are several ‘Issues’ concerning the ‘SARS-CoV-2 Antibodies’ which increasingly still require critical ‘Research Investigative Attention and Enquiry’ making the ‘Pandemic Interventional Role of Antibodies Testing’ largely continuous ‘Work in Progress’!! What are the ‘Types of Antibodies’? Some ‘Communications’ have explored the possibility of ‘Neutralizing Antibodies’ but a particular Report is highlighted for its detailed exploration of several determinants concerning the ‘SARS-CoV-2 Antibodies’ [1]!! This ‘Communication’ identified ‘Neutralizing Antibodies’ as possibilities for ‘Antibody Response’ to the ‘SARS-CoV-2 Infection’! It is further evaluated whether these ‘Neutralizing Antibodies’ actually confer ‘Individual/ Personal Immunity’ against infection by the ‘SARS-CoV-2’ and it is yet another issue what the ‘Coverage Level of Antibodies’ is that achieves ‘Herd Immunity’ for ‘Defined Populations’! The complex ‘Issues’ of how the ‘SARS-CoV-2 Antibodies’ target the ‘Receptor Binding Domain (RBD)-epitope’ and actively block the already identified ‘ACE2 Sites’ have also been reported re: the likely ‘Mechanism for Neutralization’[1]!! Whether the investigated ‘Monoclonal Antibodies (mAbs)’ are ‘Neutralizing Antibodies’ is still ‘Work in Progress’ and this needs further exploration for ‘Possible Therapeutics’ in the ‘COVID-19 Pandemic Interventions’! What about the ‘Issues’ of ‘Disease Severity’, ‘Cross-Neutralizations’, ‘Clonal Expansions’, ‘Somatic Hypermutation (SHM)’ and the ‘Neutralizing Potency’ of ‘Convalescent Serum’ which all require further investigations to successfully and sustainably address the ‘COVID-19 Pandemic’[1,2]!!
Yet another ‘Issue for Investigation’ is the ‘Optimal Time for Antibody Testing’! A recent ‘Communication’ disposed impressive data to address the ‘Issue’ viz: Only 30% ‘Antibody Positivity’ after 1 week from the ‘Onset of Symptoms’, 72% after 2 weeks and 94% after 3 weeks [3]! The existence of ‘Asymptomatic Infected Persons’ remains a ‘Difficult Public Health Challenge’ in mounting effective ‘COVID-19 Pandemic Interventions’! Impressive as these data are, and from a Cochrane Review, they are mostly from ‘Hospitalized Patients’ raising issues concerning this ‘Optimal Antibody Testing Time’ and appropriateness in relation to ‘Disease Severity’; Would this be applicable for ‘Mild and Moderate Cases’? In the Report, Antibodies were not detected after 35 days! These ‘Issues’, and several others (The Range of Studies included in the Cochrane Review, Span of the Studies up to 27th April 2020, Geographical and Population Diversity of the Studies Locations, 27 Commercial Antibody Tests among 316 Commercially Available Tests, Accuracy of the Different Tests, Sensitivity and Specificity Issues etc), were critically exposed in another recent ‘Communication’ [4]!! Indeed, more ‘Updated Systematic Reviews and Mete-Analyses’ were suggested as imperatives to further address these ‘Identified Outstanding Issues’ [4]!!!
It will be interesting to unearth the ‘SARS-CoV-2 Antibodies Profile and Pattern’ when the data for ‘SARS-CoV-2 Natural Infections’ are compared with ‘Antibodies Responses’ to the current ‘Candidate Vaccines in Clinical Trials’ re: Optimal Time for Testing, Neutralizing Status, Duration of Detectable Antibodies, Immunity Conferred on Individuals, Implications for achieved ‘Herd Immunity’ for ‘Defined Populations’ etc! The implications of these for ‘Shield Immunity’ and, indeed, the ‘Stratified Shielding’ for differentially managing the ‘Populations Protection in Easing Interventional Lockdowns’ will be worth further ‘Investigative Evaluations’ [5,6]!! A previous ‘Communication’ critically discussed the value of the ‘Differentially Distributed Burden’ in the ‘Stratified Shielding’ in the ‘Gradual Easing from Interventional Lockdowns’ with several issues exposed for further attention [7]!! Considering the ‘Genetic Diversity’ and ‘Viral Recombination Capacity’ of the ‘SARS-CoV-2’ and the ‘Vaccines Production Diversity’ (Different ‘Vaccine Precursors’: Whole Virus, Viral Gene Sequence, Viral Proteins etc), it will be quite instructive to harvest the ‘Outcomes’ of such envisioned ‘’Further Investigative Evaluations’ [8,9]!!
This ‘Communication’ is a ‘Contribution’ to the extant ‘SARS-CoV-2 Antibodies Conversations’ which are currently exploring the plethora of ‘Issues’ that are related to unearthing the ‘Facts’ to be addressed in disposing ‘Antibodies Testing’ for appropriate integration into the ‘COVID-19 Pandemic Interventions’ to achieve the desired success in the ‘Global Fight’ against the ‘Unprecedented Ravagingly Devastating 21st Century Scourge’!
REFERENCES
1. 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
2. Weitz Weitz JS, Beckett SJ, Coenen AR et al. Intervention serology and interaction substitution: modeling the role of ‘shield immunity’ in reducing covid-19 pandemic spread. medRxiv 2020.04.01.20049767 (Preprint) doi:10.1101/2020.04.01.20049767
3. 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
4. Wise J. Covid-19: Timing is critical for antibody tests, finds Cochrane review. BMJ 2020; 369:m2584
5. McKeigue PM, Colhoun HM. Evaluation of ‘stratify and shield’ as a policy option for ending the COVID-19 lockdown in the UK. medRxiv 2020.0425.20079913 (Preprint) doi:10.1101/2020.04.25.20079913
6. Smith GD, Spiegelhalter D. Shielding from covid-19 should be stratified by risk. BMJ 2020; 369:m2063
7. Eregie CO. COVID-19 pandemic and stratified shielding: some more matters for the works. https://www.bmj.com/content/369/bmj.m2063/rr-2 of 18th June 2020
8. 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
9. Eregie C.O. COVID-19 Pandemic: The difficult unresolved increasing challenges in weathering the storm. https://www.bmj.com/content/368/bmj.m1199/rr-10 of 31st March 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
16 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.
Covid-19 Pandemic, SARS-CoV-2 antibodies and testing: Still searching for more facts
The constant thread running through several rapidly evolving ‘COVID-19 Pandemic Conversations’ is the incontrovertible fact of the ‘Unprecedented Rapidly Dynamically Transmuting Specifics’ concerning the ‘Coronavirus (SARS-CoV-2)’ and the ‘Coronavirus Disease 2019 (COVID-19)’! By the day, it increasingly becomes clearer that what is yet ‘Unknown and Uncertain’ about the ‘COVID-19 Pandemic’ increasingly outpaces and dims what is ‘Known and Certain’ because of the rapidly changing and emerging ‘Pandemic Information’!! Since ‘Nature abhors Vacuum’, the ‘Unprecedented Information Gaps’ are rapidly eclipsed by ‘Unreliable Unscientific Unsubstantiated Body of Information’ now recognized as the ‘COVID-19 Infodemic’!! The World is increasingly stimulated to gear up for the ‘Huge Stressful Intellectual and Programmatic Work’ to rise to this ‘Unacceptable Public Health Challenge’ by effecting ‘Rapidly Emerging Information Outpourings’ from several ‘Enterprises’ including ‘COVID-19 Research’!!! This ‘Communication’ focuses specifically on the ‘COVID-19 Pandemic’ as it relates to ‘SARS-CoV-2’ and the investigated ‘Antibodies’.
The ‘COVID-19 Research’ on the ‘SARS-CoV-2 Antibodies’ have become part of the evolving ‘Public Health Challenge’ in this ‘Pandemic Era’! There are several ‘Issues’ concerning the ‘SARS-CoV-2 Antibodies’ which increasingly still require critical ‘Research Investigative Attention and Enquiry’ making the ‘Pandemic Interventional Role of Antibodies Testing’ largely continuous ‘Work in Progress’!! What are the ‘Types of Antibodies’? Some ‘Communications’ have explored the possibility of ‘Neutralizing Antibodies’ but a particular Report is highlighted for its detailed exploration of several determinants concerning the ‘SARS-CoV-2 Antibodies’ [1]!! This ‘Communication’ identified ‘Neutralizing Antibodies’ as possibilities for ‘Antibody Response’ to the ‘SARS-CoV-2 Infection’! It is further evaluated whether these ‘Neutralizing Antibodies’ actually confer ‘Individual/ Personal Immunity’ against infection by the ‘SARS-CoV-2’ and it is yet another issue what the ‘Coverage Level of Antibodies’ is that achieves ‘Herd Immunity’ for ‘Defined Populations’! The complex ‘Issues’ of how the ‘SARS-CoV-2 Antibodies’ target the ‘Receptor Binding Domain (RBD)-epitope’ and actively block the already identified ‘ACE2 Sites’ have also been reported re: the likely ‘Mechanism for Neutralization’[1]!! Whether the investigated ‘Monoclonal Antibodies (mAbs)’ are ‘Neutralizing Antibodies’ is still ‘Work in Progress’ and this needs further exploration for ‘Possible Therapeutics’ in the ‘COVID-19 Pandemic Interventions’! What about the ‘Issues’ of ‘Disease Severity’, ‘Cross-Neutralizations’, ‘Clonal Expansions’, ‘Somatic Hypermutation (SHM)’ and the ‘Neutralizing Potency’ of ‘Convalescent Serum’ which all require further investigations to successfully and sustainably address the ‘COVID-19 Pandemic’[1,2]!!
Yet another ‘Issue for Investigation’ is the ‘Optimal Time for Antibody Testing’! A recent ‘Communication’ disposed impressive data to address the ‘Issue’ viz: Only 30% ‘Antibody Positivity’ after 1 week from the ‘Onset of Symptoms’, 72% after 2 weeks and 94% after 3 weeks [3]! The existence of ‘Asymptomatic Infected Persons’ remains a ‘Difficult Public Health Challenge’ in mounting effective ‘COVID-19 Pandemic Interventions’! Impressive as these data are, and from a Cochrane Review, they are mostly from ‘Hospitalized Patients’ raising issues concerning this ‘Optimal Antibody Testing Time’ and appropriateness in relation to ‘Disease Severity’; Would this be applicable for ‘Mild and Moderate Cases’? In the Report, Antibodies were not detected after 35 days! These ‘Issues’, and several others (The Range of Studies included in the Cochrane Review, Span of the Studies up to 27th April 2020, Geographical and Population Diversity of the Studies Locations, 27 Commercial Antibody Tests among 316 Commercially Available Tests, Accuracy of the Different Tests, Sensitivity and Specificity Issues etc), were critically exposed in another recent ‘Communication’ [4]!! Indeed, more ‘Updated Systematic Reviews and Mete-Analyses’ were suggested as imperatives to further address these ‘Identified Outstanding Issues’ [4]!!!
It will be interesting to unearth the ‘SARS-CoV-2 Antibodies Profile and Pattern’ when the data for ‘SARS-CoV-2 Natural Infections’ are compared with ‘Antibodies Responses’ to the current ‘Candidate Vaccines in Clinical Trials’ re: Optimal Time for Testing, Neutralizing Status, Duration of Detectable Antibodies, Immunity Conferred on Individuals, Implications for achieved ‘Herd Immunity’ for ‘Defined Populations’ etc! The implications of these for ‘Shield Immunity’ and, indeed, the ‘Stratified Shielding’ for differentially managing the ‘Populations Protection in Easing Interventional Lockdowns’ will be worth further ‘Investigative Evaluations’ [5,6]!! A previous ‘Communication’ critically discussed the value of the ‘Differentially Distributed Burden’ in the ‘Stratified Shielding’ in the ‘Gradual Easing from Interventional Lockdowns’ with several issues exposed for further attention [7]!! Considering the ‘Genetic Diversity’ and ‘Viral Recombination Capacity’ of the ‘SARS-CoV-2’ and the ‘Vaccines Production Diversity’ (Different ‘Vaccine Precursors’: Whole Virus, Viral Gene Sequence, Viral Proteins etc), it will be quite instructive to harvest the ‘Outcomes’ of such envisioned ‘’Further Investigative Evaluations’ [8,9]!!
This ‘Communication’ is a ‘Contribution’ to the extant ‘SARS-CoV-2 Antibodies Conversations’ which are currently exploring the plethora of ‘Issues’ that are related to unearthing the ‘Facts’ to be addressed in disposing ‘Antibodies Testing’ for appropriate integration into the ‘COVID-19 Pandemic Interventions’ to achieve the desired success in the ‘Global Fight’ against the ‘Unprecedented Ravagingly Devastating 21st Century Scourge’!
REFERENCES
1. 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
2. Weitz Weitz JS, Beckett SJ, Coenen AR et al. Intervention serology and interaction substitution: modeling the role of ‘shield immunity’ in reducing covid-19 pandemic spread. medRxiv 2020.04.01.20049767 (Preprint) doi:10.1101/2020.04.01.20049767
3. 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
4. Wise J. Covid-19: Timing is critical for antibody tests, finds Cochrane review. BMJ 2020; 369:m2584
5. McKeigue PM, Colhoun HM. Evaluation of ‘stratify and shield’ as a policy option for ending the COVID-19 lockdown in the UK. medRxiv 2020.0425.20079913 (Preprint) doi:10.1101/2020.04.25.20079913
6. Smith GD, Spiegelhalter D. Shielding from covid-19 should be stratified by risk. BMJ 2020; 369:m2063
7. Eregie CO. COVID-19 pandemic and stratified shielding: some more matters for the works. https://www.bmj.com/content/369/bmj.m2063/rr-2 of 18th June 2020
8. 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
9. Eregie C.O. COVID-19 Pandemic: The difficult unresolved increasing challenges in weathering the storm. https://www.bmj.com/content/368/bmj.m1199/rr-10 of 31st March 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