Greka Engineering and Technology, 28 Landmark Plaza, Outer Ring Road 1, CBD, Zhengzhou, 450000, China.
Current standard vaccine testing protocols take approximately 10-24 months of testing before a vaccine can be declared successful. Sometimes by the time a successful vaccine is out for public use, the outbreak may already be over. With no vaccine or antiviral drug available to treat the infected, we are left with the age-old methods of isolation, quarantine, and rest, to arrest such a viral outbreak. Convalescent blood therapy and covalent plasma therapy have often proved effective in reducing mortality, however, the role of innate and adaptive immune cells in these therapies have been overlooked. Antigen presenting cells (APCs), CD4+ T memory cells, CD8+ T memory cells, and memory B-Cells all play a vital role in sustainable defense and subsequent recovery. This report incorporates all these aspects by suggesting a novel treatment therapy called selective convalescent leukapheresis and transfusion (SCLT) and also highlights its potential in vaccination. The anticipated advantages of the proposed technique outweigh the cost, time, and efficiency of other available transfusion and vaccination processes. It is envisioned that in the future this new approach could serve as a rapid emergency response to subdue a pathogen outbreak and to stop it from becoming an epidemic, or pandemic.
Keywords: Convalescent Blood, WBC, Leukapheresis, Transfusion therapy, Vaccination, COVID-19
Four factors can make a novel pathogen outbreak extremely deadly: a) high reproduction number or Ro factor (Ro≥3); b) high mortality rate (≥50%); c) long incubation period (≥10 days); and d) asymptotic spreading. If a pathogen has any three of these four characteristics, it can be classified as Pathogen-X, i.e., a pathogen which has the potential to cause mass extinction. One of the hypotheses to explain past mass extinctions of certain species (recent and geological) is highly infectious disease outbreak [1-5].
Currently the world is facing one of the worst pandemics in human history. As of 25th July 2021 the officially reported cases of Corona Virus Pandemic or COVID-19 has touched nearly 194 million with about 4 million related deaths worldwide. Not to mention the billions of lives who are suffering due to the adverse effects of economic turmoil and disruption of normal livelihood; and there seems to be no end in sight. As scientists we can ask ourselves: Shouldn't we be better prepared? Isn't this a wakeup call for the scientific community?
Current standard vaccine testing protocols take nearly 10-24 months of testing before a vaccine can be declared successful. Sometimes by the time a successful vaccine is available for public use, the outbreak may already be over. A good example is the 'Spanish flu' or the 1918 influenza pandemic, which wreaked havoc over a short span of two years. The flu was caused by an H1N1 virus with genes of avian origin and can be categorized as the most severe pandemic in the last two centuries. Spanish flu infected around 500 million people worldwide, or one-third of the world's population, and nearly 50 million people died . No vaccine or antiviral drug was available to treat the infected. Isolation, quarantine, and rest were applied to arrest the viral outbreak. However, doctors around the world also used blood products from survivors, which helped to reduce the mortality rate by as much as 50%. Similar approaches using 'convalescent blood plasma therapy' have been reported in the treatment of viral outbreaks like Ebola [7,8] (Mupapa et al., 1999; van Griensven et al., 2016).
Can the human race (species) afford long testing protocols when struck with a deadly pathogen like a novel pathogen-X? This paper suggests a hypothesis of a possible option to minimize the rate the spread of a disease like COVID-19, if not completely stop it.
Techniques like 'monoclonal antibody technique' or 'covalent plasma therapy' all focuses on administration of 'antibodies' from survivors to patients. However, during these transfusion techniques, little attention is paid to the generating mechanism of the antibodies. When convalescent blood transfusion therapy is applied, one, or all, of the following three things could be happening (Figure 1):
Some medical scientists argue that factor I is the only factor responsible for a successful recovery. It is unclear whether 500 mL or 1 L of new blood holds sufficient antibodies to overrun the pathogen population without a further increase in their numbers. Antibodies cannot generate more antibodies, unless there is a copying mechanism that is still unknown to medical science. Therefore, it is seems most likely that 'knowledge transfer' (factor II) leads to a sustainable defense (Figures 1 & 3) and subsequent recovery. Some recent research reviews in medical science [16,17] (viz. Grifoni et. al 2020, Sette and Crotty 2020) seem to support this conjecture (factor II) and highlights the possible role memory CD4+ and CD8+ T-cells in the immune response against COVID-19. Furthermore, studies of techniques such as T-cell engineering  highlight the importance of factor II in therapeutic uses against cancer cells.
Hypothesis on what might be happening during convalescent blood transfusion therapy. Reprinted from Mukherjee .
Whole blood and its components. Courtesy: http://givingblood.org/about-blood/blood-components.aspx.
Schematic steps for Leukapheresis and enrichment process in engineered T-Cell therapy for cancer treatment. For details please refer to research papers like Fesnak et al. .
Based on the aforementioned hypothesis, I propose selective convalescent leukapheresis and transfusion (SCLT) as a rapidly deployable therapeutic treatment for highly infectious diseases like COVID-19, Ebola, influenza, SARS, and MERS. The technique would involve:
Stage 1: selection of a suitable donor, i.e., a survivor with a strong immune system. In other words convalescent blood should be taken from survivors who exhibited mild symptoms, quick recovery, and have no underlying conditions or other transmittable disease like HIV, HPV, etc.
Stage 2: the whole blood (Figure 2) should be subjected to fractional separation by suitable leukapheresis processes  to extract the convalescent WBCs (Figure 3). If required, this process could be repeated by collecting convalescent blood from different donors until sufficient convalescent WBC was available for transfusion.
Stage 3: the transfusion of the convalescent WBC. The convalescent WBC can be administered in different quantities based on whether it is used for therapeutic treatment or for the purpose of vaccination (Table 1).
The proposed SCLT technique has the following potential advantages:
Anticipated dosage of white blood cell (WBC) + plasma from convalescent blood (caution: must be tested clinically for safe use)
|Patient age group 0-10 years||Patient age group 11-50 years||Patient age group 51-65 years||Age >65 years|
|Already infected patient (for treatment)||Dosage: small amt. of WBC + small amt. of Plasma||Dosage : medium amt. of WBC + medium amt. of Plasma||Dosage: medium amt. WBC + large amt. of Plasma||Dosage: medium amt. WBC + very large amt. of Plasma|
|Critical Condition: 2 dosage/day||Critical Condition: 3 dosage per day||Critical Condition: 4 dosage per day||Critical Condition: 4 dosage per day|
|Normal Condition: 1 dosage/day||Normal Condition: 2 dosage per day||Normal Condition: 3 dosage per day||Normal Condition: 3 dosage per day|
|Mild Condition: 1 dosage/day||Mild Condition: 1 dosage per day||Mild Condition: 2 dosage per day||Mild Condition: 2 dosage per day|
|small amt. of WBC||small amt. of WBC||small amt. of WBC||small amt. of WBC|
Here, WBC: WBC derived from convalescent blood.
Blood components and simple Boolean logic to emphasize the importance of convalescent white blood cells (WBCs).
Clearly, the possible side effects of GVD must be carefully considered prior to administration of WBC for therapeutic use. Furthermore it is very important to note that the SCLT technique in not a panacea and is just an alternative approach which can be used for vaccination and treatment against diseases like COVID-19.
Since the release of papers Mukherjee 2020 [10, 11] in March 2020 in open access journals; the SCLT hypothesis has been scrutinized by experts; and its EQA (External Quality Assessment) is currently being tested in some medical laboratories/organizations like Saint Louis University Center for Vaccine Development and Duke Health (Duke University Health System). Call for human trials [14, 15] have already begun for vaccine development.
In the absence of readily available vaccines or cures against a deadly novel pathogen, SCLT could not only act as a first line of defense but could potentially be used to vaccinate human populations against diseases like COVID-19, influenza, SARS, MERS, Ebola, etc. If applied correctly, this technique may be able to prevent a pathogen disease outbreak from turning into an epidemic or pandemic. However, before trying this technique on humans, it is mandatory that medical scientists must carefully consider the side effects of WBC related transfusion.
The author is grateful to the medical world for their kind support; and their tireless effort in the ongoing fight against COVID-19. The author would like to dedicate this paper to his Late father Lt. Col. Ashis Prarthi Sinha who has been constant source of inspiration for him. Special thanks to Ms. Wang Xian Yo, Ms. Du Xiao Shuang and Mr. Randeep Singh Grewal (CEO Greka Group) for their encouragement and constant support. The author would like to express his gratitude to Ms. Sayme Perez, and Ms. Shireen Aziz for the patience they displayed with author's long list of “never ending” queries related to medical science.
The author gives guarantee of the following ethical statements which are true to the best of his knowledge:
Date: 26th Mar 2020,
Signed: Dr. Arka Prava Mukherjee.
The authors have declared that no competing interest exists.
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9. Mukherjee AP. Training the immune system: an alternative approach to counter COVID-19 (2019-nCOV), MERS, SARS, Influenza-A/B, Ebola. 2020. Preprint submission, Researchgate. DOI: https://doi.org/10.13140/RG.2.2.13997.23525.
10. Mukherjee AP. Hypothesis: Immunotherapy by Selective Convalescent Blood Engineering to stifle diseases like COVID-19. 2020. Preprint submission, Researchgate. DOI: https://doi.org/10.13140/RG.2.2.16569.11368.
11. Mukherjee AP. Hypothesis: Immunotherapy by Selective Convalescent Blood Engineering to stifle diseases like COVID-19. 2020. Preprint submission, OSF Preprints. DOI: https://doi.org/10.31219/osf.io/s7jwz.
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13. Casadevall A, Pirofski L. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 DOI: https://doi.org/10.1172/JCI138003
14. Leukapheresis Protocol - Clinical Trial: Testing leukapheresis fluid (cells) of the immune system to support vaccine development. Duke Health. Year 2020. Protocol Number: IRB: PRO00000873. https://www.dukehealth.org/clinical-trials/directory/pro00000873
15. Clinical Trials -SLU: Leukapheresis study for those who have tested positive to COVID-19 (18-65 years old). Year 2020, Refer to study IRB #27790. https://www.slu.edu/medicine/internal-medicine/infectious-disease/vaccine-development/current-studies.php
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17. DOI: https://doi.org/10.1016/j.cell.2020.05.015
18. Sette A, Crotty S. 2020 Pre-existing immunity to SARS-CoV-2: the knowns and unknowns. 2020, Nature Reviews: Immunology, Vol. 20, 457-458. DOI: https://doi.org/10.1038/s41577-020-0389-z.
Corresponding author: E-mail: arka_pravacom; apmcom; Phone: +86-18503861302.