Vaccines, convalescent plasma, and monoclonal antibodies for covid-19BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2722 (Published 09 July 2020) Cite this as: BMJ 2020;370:m2722
All rapid responses
Professor Sewell et al have rightly urged caution with respect to the role of antibodies . As they point out, use of convalescent plasma or monoclonal antibodies, not to mention the induction of antibodies via vaccination, have potential for both therapy and pathogenic antibody-dependent enhancement (ADE).
However, ADE has also been observed during the course of infection in over 40 types of virus, including other coronaviruses. It occurs when the binding of antibodies to viral surface proteins can promote viral invasion into host immune cells instead of preventing it. Once the virus has entered the cells, infectivity is enhanced as it can now replicate and destroy the immune cell, known as the ‘Trojan horse strategy’.
ADE was found with both the SARS-CoV-1 and MERS epidemics, with high antibody titres correlating with disease severity and increased tissue injury, with the entry of virus/antibody complexes promoting inflammation. It was suggested that ADE was one of the mechanisms causing hyperactivation of macrophages and monocytes, leading to the often fatal cytokine storm. [2-4]
Are we seeing this in COVID-19? Possibly. Study after study reports that the magnitude of antibody titres correlates with disease severity and worse outcome, with elevated pro-inflammatory cytokines, which may lead to organ damage/failure as well as respiratory failure. [5-7]
However, elevated antibodies could just reflect the immune system working overtime to destroy the virus. Evidence against this includes the fact that the increase in antibody titres occurs so frequently in convalescent or recovered patients, when one would presume that the virus had been vanquished. Furthermore, relatively low antibodies are normally associated with high viral clearance rate, while a stronger antibody response is associated with delayed viral clearance and greater disease severity or mortality, indicating that higher antibody titres are not required for viral clearance. This gives credence to the ADE hypothesis. [3,7-10]
We also know that autoantibodies may develop in severe infection, impeding the immune system, attacking proteins in the blood vessels, heart and brain (the organs most affected by COVID-19), damaging the phospholipids known to control blood clotting (another potential problem in severe COVID-19) and attacking annexin A2 (the protein which ensures the integrity of small blood vessels in the lungs). [11-14] The presence of autoantibodies also causes concern with respect to the initiation or worsening of various autoimmune conditions in COVID-19; an Israeli study found that SARS-CoV-2 triggers autoimmunity in some predisposed individuals. It has also been proposed that ADE could be responsible for long COVID. [11,12,15-17]
One of the most potentially fatal autoimmune conditions induced by COVID-19 and other viral infections is immune thrombocytopaenic purpura (ITP), possibly better known as a vaccine reaction. A Systematic Review of COVID-19 ITP patients found that the majority were older and with more severe disease, while a Russian post-mortem study found autoimmune damage in the lungs, kidneys, liver, adrenal gland and intestines of COVID-19 patients. [18,19]
The reasons why ADE may take place are currently unknown and we still do not know what might protect us from ADE. A clue might lie in the fact that recovery following mild COVID-19 is characterised by optimised immune functioning, whereas severe outcomes are associated with dysregulated immune responses, particularly excessive cytokine production and suboptimal T cell responses, including Th2-skewing.  Interestingly, a study of UK healthcare workers showed that vitamin D deficiency was the only independent risk factor for increased production of COVID-19 antibodies.  Possibly the absence of adequate vitamin D levels triggers the immune dysregulation seen with ADE.
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Competing interests: No competing interests
Plasma from Healthy Young People and Human Thymopoiesis as Potential Therapy Against COVID-19: Further and Concrete Up-To-Date Scientific Support
I have previously postulated that the administration of plasma from healthy young people and children might offer a treatment for patients infected with COVID-19 (1). This conjecture was based on the fact that COVID-19’s infectivity among young people and children is uncommon and it appears that this group is insusceptible to it (2-4). This insusceptibility to SARS-CoV-2 might be related to the fact that the thymus gland and its hormones remain active during puberty where the thymus grows and reaches its maximum size and then starts to atrophy (involution). Since the thymus is the primary site of de novo naïve T cell production (5), the presence of thymic hormones in the blood pool might be the reason for the resistance of this group to COVID-19. Hence, blood plasma obtained from this group administered to moderately and severely diseased patients suffering from COVID-19 might offer a cure.
Further evidence and support related to this postulate will be presented here from up-to-date data and research. As noted previously (1), this approach is totally different than convalescent plasma or CP such as the one discussed by Sewell et al. (6). Also CP is not feasible since only 1% of recovered patients has enough levels of antibodies to possibly neutralize the virus and their levels declined quickly, which was the case for the majority of patients tested for the presence of COVID-19’s antibodies (7, 8).
The human immune system is comprised of two compartments: the myeloid and the lymphoid progenitors where both play essential and vital roles against all types of infections (9). The lymphoid progenitor produces lymphocytic B and T cells where both originate from the bone marrow. The B cells (bone marrow derived) and T cells (thymus derived) mature in the bone marrow and the thymus, respectively. The B lymphocytes upon activation differentiate into plasma cells that secrete antibodies while the T cells encompass 2 classes of cells where one differentiate into cytotoxic T cells killing cells infected with viruses while the other class differentiate and activate other cells such as B cells. The myeloid progenitor produces granulocytes, dendritic cells, macrophages and mast cells.
Recovered COVID-19 patients do not produce robust antibodies that can manifest themselves for a prolonged period of time, making it difficult to produce an effective vaccine (8, 10). The immunity developed from COVID-19 infection is suboptimal, dysfunctional and short-lived (8, 10). This surprising observation might be explained by the finding that only the myeloid response is hyperactivated while the lymphatic response is silenced (11). In essence, myeloid cell-mediated attacks the virus directly and causes significant inflammatory body response, creating a cytokine storm and resulting in higher morbidity for elderly and severely diseased patients.
It appears that the virus somehow is engineered to attenuate the lymphatic response and concurrently stimulate the myeloid response, which might explain the cytokine storm and at the same time the absence or low levels of antibodies for moderately and severely diseased patients. This also might lend support to the fact that elderly patients are much more susceptible to SARS-CoV-2 than younger ones since T cells production ceases with increasing age, T cell senescence.
Transient lymphopenia is a common feature in most respiratory viral infections which occurs 2 to 4 days around the onset of symptoms and rapidly subsides (12); however, this is not true with COVID-19. Lymphopenia associated with COVID-19 is more pronounced and is prolonged, especially with severely diseased patients, and seems to be more selective towards T cell lineages (13), emphasis added. In the case of COVID-19, lymphopenia is rarely observed in infected children where the mortality rate is almost zero, while in the elderly where the mortality rate is high, lymphopenia occurs more frequently with moderately and severely diseased cases, and always associated with significant decrease in T cell counts (14).
Stress has also a profound effect on T cell functions and atrophy of the thymus. This as a result will negatively affect the homeostasis of the immune system, the production of T cells and therefore the lymphatic response to infections. Indeed, this was observed with COVID-19’s infectivity (15).
Collectively, it can be concluded that T cells impairment and downregulation are the culprit and might be the major player in the treatment of COVID-19. It is well documented that T cells that survive the selection process in the thymus differentiate into CD4+ or CD8+ single positive T cells. Studies have shown that both CD4+ T and CD8+ T memory cells were found in 100% and 70% of COVID-19’s recovered patients, respectively (16). These cells are essential in protective immunity and the production of antibodies. Hence, the mounting evidence presented here supports the supposition suggested earlier regarding the notion that administration of plasma obtained from healthy young people might enhance human thymopoiesis and might treat patients suffering from COVID-19, producing T cells and their differentiating counterparts CD4+ and CD8+ cells (1). As a side note, it is also anticipated that this method of treatment might be able to alleviate stress-mediated inflammatory response to COVID-19, viz., psychoneuroimmunology (17).
Accordingly, the treatment scheme suggested here might excite and fine-tune the lymphatic response rather than the myeloid one in moderately and severely diseased COVID-19 patients, and thereby treating COVID-19 and eventually producing antibodies that can neutralize SARS-CoV-2. As mentioned earlier, almost all moderately and severely COVID-19’s patients are age advanced, which is associated with impaired T cells and downregulation of both CD4+ T and CD8+ T cells responses. Previously, it was found that growth hormone (GH) therapy can in fact enhance thymopoiesis, thus increasing thymic hormonal output and the production of de novo naïve and total CD4+ T cells, which in turn facilitated immune restoration in HIV-1 patients (18). The study concluded that thymic involution can be pharmacologically reversed and thymic function can be restored in immuno-deficient patients (18). Thus and according to above newly published research on COVID-19, it is more than likely and highly plausible that plasma procured from young people might enhance human thymopoiesis and treat patients suffering from COVID-19.
1. Batarseh KI. Plasma from healthy young people and human thymopoiesis as potential therapy against COVID-19. BMJ. Published Online July 13, 2020. https://www.bmj.com/content/368/bmj.m1252/rr-29
2. Rasmussen S, Thompson L. Coronavirus disease 2019 and children what pediatric health care clinicians need to know. JAMA. Published Online April 3, 2010. file:///C:/Users/layla/Downloads/jamapediatrics_rasmussen_2020_vp_200009.pdf
3. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. Published Online February 28, 2020. https://www.nejm.org/doi/pdf/10.1056/nejmoa2002032
4. Xu Y, Li X, Zhu B, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med 2020. https://doi.org/10.1038/s41591-020-0817-4
5. Tesselar K, Miedema F. Growth hormone resurrects adult human thymus during HIV-1. J Clin Invest 2008: 118(3): 844-847. https://www.jci.org/articles/view/35112/pdf
6. Sewell H, Agius R, Kendrick D, et al. Vaccines, convalescent plasma, and monoclonal antibodies for covid-19. BMJ 2020;370:m2722
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9. Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York, NY: Garland Scienc. The components of the immune system (2001). https://www.ncbi.nlm.nih.gov/books/NBK27092/
10. Long, Q., Tang, X., Shi, Q, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 2020. https://doi.org/10.1038/s41591-020-0965-6
11. Haseltine W. The way that COVID-19 tricks the immune system could result in more severe illness. Forbes 2020. https://www.forbes.com/sites/williamhaseltine/2020/05/27/a-nasty-trick-i...
12. McClain M T, Park LP, Nichoson B, et al. Longitudinal analysis of leukocyte differentials in peripheral blood of patients with acute respiratory viral infections. J Clin Virol 2013; 58(4): 689–695. 10.1016/j.jcv.2013.09.015
13. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130: 2620–2629. 10.1172/JCI137244
14. Tavakolpour S, Rakhshandehroo T, Wei E, et al. Lymphopenia during the COVID-19 infection: What it shows and what can be learned. Immunol Lett 2020; 225: 31–32. 10.1016/j.imlet.2020.06.013
15. Debnath M, Berk M, Maes M. Changing dynamics of psychoneuroimmunology during the COVID-19 pandemic. Brain, Behavior & Immunity 2020. https://doi.org/10.1016/j.bbih.2020.100096
16. Grifoni A, Weiskopf D, Ramirez S, et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020; 181: 1489–1501.e15. https://doi.org/10.1016/j.cell.2020.05.015
17. Ader R. Psychoneuroimmunology. New York, NY: Academic Press (1981b).
18. Napolitano L, Schmidt D, Gotway M, et al., Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest 2008; 118(3): 1085-1098. https://www.jci.org/articles/view/32830/pdf
Competing interests: No competing interests
I read with interest the editorial on vaccines and passive immunity (1), which ‘injected’ a note of caution in the expectations of the public. Professor Sewell et al give the triple warnings of vaccines being less effective in those with greatest need (ie older age groups), having likely short term protective immunity or even injurious effect, and the need for careful timing of treatments such as convalescent plasma to avoid progression to a overactive immune-inflammatory response (cytokine storm) with consequent severe organ damage in those predisposed.
While intensive research for effective and safe vaccines continues, in addition to public health measures, we should search widely for ways to ameliorate the underlying pathological processes at an early stage in those affected. Mast cells are known to be the main source of cytokine release that leads to lung damage in SARS-Co-V2. Mast cell stabilisers together with mediator blockers may therefore help to ameliorate the pro-inflammatory effects of covid-19.
Mast cells are the sentinels lining mucosal and connective tissues throughout the body, including the respiratory tract, being located at the junction point of the host and external environment at places of entry of antigen. They are heterogeneous, multifunctional immune master-cells containing an exceptionally large number of granules which store preformed and other inflammatory mediators and equally have a large number of interactions. Their physiological functions include regulation of vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis, and venom detoxification. On activation, mast cells release preformed histamine, proteases, (chymase, tryptase, and carboxypeptidase A type), and later, proinflammatory cytokines including IL-1, IL-6, leukotrienes and TNF α
In the respiratory tract, the immune response to mast cell activation results in airway constriction, increased mucous production, rhinorrhoea, fever and cough. Mast cell degranulation increases vascular permeability and local oedema, which can obstruct nasal airways and lead to congestion. There is increased production of mucus and its accumulation may block off the sinuses and result in a bacterial infection.
Mast cell stabilisers and mediator blockers, such as antihistamines and anti-leukotrienes, are widely used in allergic conditions and mast cell disorders, which may have similar respiratory symptoms, and are therefore logical substances to consider in the fight against SARS-CoV-2. (2)
Mast cell stabilisers include Vitamin D (3), ketotifen (also an antihistamine), sodium cromoglycate, quercetin, luteolin. Vitamin C also has a role in mast cell stabilisation. These could be trialled individually or in combination at an early stage of infection in a patient with moderate symptoms or on admission to assess effect on the subsequent course.
1. Vaccines, convalescent plasma, and monoclonal antibodies for covid-19 https://www.bmj.com/content/370/bmj.m2722
2. Mast cell stabilisers, leukotriene antagonists and antihistamines: A rapid review of the evidence for their use in COVID-19 https://www.cebm.net/covid-19/mast-cell-stabilisers-leukotriene-antagoni...
3. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) https://www.frontiersin.org/articles/10.3389/fimmu.2020.01451/full
Competing interests: No competing interests
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’ !! 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 ! 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’ ! 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’ !! 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  and ‘Vaccines against Other RNA Viruses’ were also not successful with some even causing ‘Disease Exacerbations’ from ‘Antibody-Dependent Enhancement (ADE)’ !! 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’  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’ !! 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’ !! 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 !!
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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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’. https://www.bmj.com/content/370/bmj.m2668/rr-0 of 21st July 2020
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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
The ongoing pandemic of Coronavirus disease-2019 (COVID-19) has threatened millions of lives globally. An effective vaccine against COVID-19 is need of the hour. India has been a hub for vaccine productions and Indian pharmaceutical companies have contributed immensely to the vaccine related projects running all over the world. Indian companies have also been pioneers in starting working on COVID-19 vaccine and finishing preclinical trials1. Recently, two indigenous COVID-19 vaccines, Covaxin by Bharat Biotech and ZyCoV-D by Zydus, Cadila, have got regulatory approval to enter Phase I/II human clinical trials1. COVID-19 cases are surging fast in India, hence the commencement of the clinical trials for the vaccine has raised great hope and brought a sense of relief in the common people. However, as any proposed viral vaccine may have important safety risks for the clinical trial participants, and subsequent users, related issues have now come to the fore.
It has been a global understanding among medical institutions and research organizations that sticking to the guidelines set by World Health Organization (WHO) for human clinical trials for any vaccine is a must2, and any haste in that may be risky. Also, keeping to the standard ethical principles in selecting clinical trial participants, following up for the adverse effects, taking due care of their safety, and eligible scrutiny of the trial results are the mandatory concerns which cannot be overlooked. It is also necessary that the health centres chosen for the vaccine trial should have prior experience in running clinical trials2.
Surprisingly, Indian Council of Medical Research (ICMR), the top medical research regulatory body of the country, has asked participating health centres for setting a target completing all three phase clinical trials for Covaxin until 15th August, 20203,4. Covaxin has been developed in partnership with ICMR’s National Institute of Virology (NIV). The hastened approach by the regulatory body has astonished medical experts, biological scientists, and scientific organizations of the country 4 . However, later, the regulatory body has clarified on the issue and said that it was only an attempt to fast track the process, and any deadline has not been fixed. The organization has also assured that the quality of the vaccine and participant’s safety will not be compromised5. We hope that, hereafter the standard operative procedures will be followed and participants’ safety will remain a priority for the COVID-19 vaccine clinical trials in the country.
1. India approves second Covid-19 vaccine for clinical trials [Internet]. [cited 2020 Jul 6];Available from: https://www.clinicaltrialsarena.com/news/india-trials-second-covid19-vac...
2. WHO Expert Committee on Biological Standardization Sixty-seventh report /Guidelines on clinical evaluation of vaccines: regulatory expectations. https://www.who.int/biologicals/expert_committee/WHO_TRS_1004_web_Annex_...
3. Bharat Biotech ICMR [Internet]. [cited 2020 Jul 6];Available from: https://www.scribd.com/document/467859231/Bharat-Biotech-ICMR#download&f...
4. India’s Foremost Science Academy Calls ICMR’s August 15 Vaccine Deadline “Unfeasible” [Internet]. [cited 2020 Jul 6];Available from: https://thewire.in/science/indian-academy-of-sciences-covid-19-vaccine-i...
5. ICMR press release, July 4, 2020. [cited 2020 Jul 6];Available from: https://www.icmr.gov.in/pdf/press_realease_files/ICMR_Press_Release_0407...
Competing interests: No competing interests