A Therapeutic Approach from Lab to Clinic in the Domain of the Disease Caused by the Novel Coronavirus from the Perspective of an Egyptian Scientist

Laila Mahmoud Montaser

Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Egypt

*Correspondence to: Dr. Laila Mahmoud Montaser, Prof. of Clinical Pathology, Chair of Stem Cell, Regenerative Medicine, Nano medicine and Tissue Engineering (SRNT) Research Group, Faculty of Medicine, Menoufia University, Egypt.

Copyright © 2020 Dr. Laila Mahmoud Montaser. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Perspective 1
There was a problem started by Pneumonia of unknown cause detected in Wuhan, China. Every morning we wake up to the news about the contemporary pandemic in serious pneumonia caused by coronavirus. The coronavirus now is pandemic killed and infected thousands people according to World Health Organization (WHO). The coronavirus is a newly identified pathogen and there is no known pre-existing immunity in humans. Infection rates and death toll are rising. This crisis affects our attitude and our practice, as it certainly affects our lives. WHO characterizes COVID-19 as pandemic and so calls for urgent, aggressive actions to combat the virus [1]. Presently there are no vaccines or drugs available for COVID-19. Therefore, proposal of a therapy with accessible, rationale and applicable technique is urgently needed.

I was trying to discover how I would write about coronavirus in my novel Editorial as I have some things to say, and then Chinese doctors made it easy by using convalescent plasma (CP) to cure several people on their death beds. Chinese physicians have several trials ongoing using plasma to treat the disease. Early results look promising in curing the illness.

With a vaccine for COVID-19 up to this time a lengthy path from being recognized, I am handling to inspirit a century-old blood-derived therapy for use in hopes of slowing the propagation of the disease.

Under this circumstance, I hypothesize that platelet-rich plasma (PRP) rich in growth factors (convalescent plasma) from recovered patients proposed as a therapy for new COVID-19 patients.

The overall work-flow involved in the cure of new COVID-19 patients using blood plasma from recovered patients is schematically represented in Figure 1.

Human whole blood is produced by venipuncture of blood from recovered patient and then subject to two sequential centrifugation steps (i.e. separation and concentration). The first centrifugation separates pellet plasma, leukocytes, and platelets from the erythrocytes. The second centrifugation collects concentrated platelets in a small volume of plasma (designated as PRP). Activation of the prepared PRP is applied by CACl2 then rapidly administer to the new COVID-19 patient.

My objective is to establish an optimized method for treating new coronavirus patients using convalescent plasma (CP) from recovered patients suitable as a therapy for new COVID-19 patients.

The scope of the proposal is to develop and utilize the CP from recovered patients, which could alleviate the problems associated with the helplessness of fully licensed treatments or vaccines against the new coronavirus. CP is proposed alternative for curbing COVID-19.

Convalescent Plasma (CP) Preparation Protocol
CP prepared as per the protocol standardized and optimized in my Laboratory. CP is produced by drawing 100ml of blood (up to five multiples) from the recovered patient and then placing it in the centrifuge. This machine spins the blood at a rapid speed causing the platelets, growth factors, and WBCs to be separated from the rest of the blood products. Once introduced into the new COVID-19 patient, the platelets then release more growth factors and signaling proteins that basically tell the body to send in the stem cells and create the therapy process.

Steps of Preparation of Convalescent Plasma (CP)

100ml whole blood is collected by venipuncture in the presence of anticoagulants in ten 10ml plain sterile plain tubes each containing anticoagulant, 1500µl acid citrate dextrose (ACD) 10ml blood in each tube. Thereafter, a two-step centrifugation procedure occurs. The 10 tubes were 1st centrifuged with low forces (soft spin) at 200g for 15 minutes to separate plasma from sediment other blood cellular components. The 1st centrifugation yields three layers: RBCs (red blood cells), “buffy coat” (white blood cells and platelets) and PPP (platelet poor plasma); hence, PPP and “buffy coat” (upper layer) transfer by sterile syringes into another plain sterile tube and underwent a 2nd hard spin centrifugation (high centrifugal force) at 1200g for 10 minutes. Then the supernatant containing PPP is discarded; keeping only some plasma at the bottom of each tube. The platelet pellet is re-suspended in the plasma left i.e. mixing the platelets into lower 1/3rd of plasma. Finally, CP is collected in one plain sterile tube. Just before injection into the new coronavirus patient the resulting CP is suspended and activated by CACl₂ (50µl) for each 1ml PRP.

Although every expertise is different, but my pioneer deep-experience since more than one decade in the field of preparation, application, and implementation of CP as an example of a scientific and research success [2-7] may provide important historical precedents that are promising, optimistic and valuable as mankind now challenges the COVID-19 pandemic.

Success Story - Putting Technology into Practice [3-7]
The M.Sc. of Clinical Pathology, which was discussed in early time February 2016 themed “Platelet-rich plasma preparation applications in knee osteoarthritis” under my supervision as the main supervisor and chief scientist who selected the subject of the research, the jury board had recommended the adoption of the thesis and for being fabulous scientific breakthrough with 92.8% success rate for the first time in Egypt, addresses the Faculty Council before the end of February 2016 to put into clinical implementation in patients of knee Osteoarthritis. And Department of Clinical Pathology announced its full readiness to participate with clinical departments in the practical application of this technique for being a scientific prestigious achievement for Menoufia Faculty of Medicine and the Department of Clinical Pathology

Accordingly, now this CP promising method becomes low priced routine test in our Clinical Pathology, Hematology, and blood banking laboratories of Menoufia University hospitals for cure of patients. Designation of this choice relies on criterion blood-banking coaching.

Research by Prof Jishou and his team at Nankai University in Tianjin shows novel virus has converted gene identical to those found in HIV and Ebola. Findings may aid to clarify how much the contagion has expansion, wherever it derive from and how much preferable to combat that [8].

Molding of antibody-laden blood has been applied with notified successfulness in previous outbursts [9]. Medicinal letters issued through the Spanish flu pandemic of 1918 contains condition records characterizing how much transformation of blood outputs gained from survivors may have participated to a 50% decrease in demise between sorely sick cases. In 1934, a measles burst at a Pennsylvania school was stopped while plasma gained of the initial contaminated pupil was utilized to cure chum pupils. Lately, treatment by plasma was utilized to remedy sick persons in the course of outbursts of Ebola and avian flu. To originating therapies for Covid-19, the top streak of safeguard may be the plasma derived remedy [10].

During February 2020, doctors in Shanghai prepared CP to treat recent contaminated cases with the virus. As stated by to SHANGHAI/GENEVA (Reuters) - A Chinese professor said Doctors in Shanghai are utilizing infusions of blood serum from persons whom have convalescent from the coronavirus to cure these yet battling the infection, announcing several supporting preparatory outcomes. The president of a Wuhan hospital has notified serum infusions from convalescent cases have demonstrate several reassuring initial findings. He told “We are confirmed such way can be highly successful in our sick persons”. Dr. Mike Ryan, head of WHO’s health emergencies program reported in Geneva, CP has been proven effective and life-saving against other infectious diseases, including rabies and diphtheria, it is a very important area to pursue. A topmost contingency expert at the WHO state subsequently that employing CP was a highly useful tactic to experiment, but that it was substantial to bring the time quite to increase the improve of a case’s immunity. So it should be designated at the quite timing, as it wipers up the virus in the system, and it merely grants the novel case’s immune system a pivotal drive in the timing it necessary. However it has to be accurately timetabled [1].

The Japanese drug maker Takeda Pharmaceutical Co. reported developing a new coronavirus drug derived from the blood plasma of people who have recovered from Covid-19. The drug will harness the antibodies of recovered coronavirus patients. As stated by Takeda, plasma-derived remedies have formerly manifests effectiveness facing another serious critical viral respiratory infections, working those applicable therapy choice for utilize opposed to COVID-19 [11].

Presently, Regenerative Medicine symbolizes a transfer in respect of better approachable, inexpensive, and frequently beside a bed tactics to tissue repair. CP is incorporated into the domain of regenerative medicine. It is an autologous focus of human being platelets included in a little bulk of plasma. The major features of CP involve its accessibility, affordability, and less incursive output, as it is gathered from the sick person’s blood intravenously. CP is safe with no serious complications. As the making method is fast and seeks simple apparatus, CP can be infused to a sick person in no more than few hours of the resolution of therapy. These advantages activate CP highly desirable for application in a set of situations including hospitals, outpatient clinics, and in different regions escorted by restricted supplies. As the therapy is newly ready for every case so no necessity for inventory [3].

My point of view debates that CP is a selection for safeguard and therapy of COVID-19 which could be speedily available if there are enough numerals of cases who have improved. My technique is established on the thought that antibodies progressed by recuperated cases may prop the immune system of novel sick persons. The method harnesses antibodies from the blood plasma of persons who have recuperated from COVID-19 disease to elevate the immunity of recently contaminated cases and these ones at hazard of concluding the illness. The antibodies included in the plasma of blood possess the power to link to and equalize the virus that responsible for COVID-19. A defiance of the method is that exact time is significant orderly to increase the support to a sick person’s immunity. The therapy is not visualized as an antidote to treating coronavirus, but a tentative step that could support until robust options such as vaccines are available.

CP can be given in a preventive modality to prohibit contagion in high-risk patients, such as susceptible persons with hidden medicinal states, validity auspice suppliers, and persons with exposition to assured patients of COVID-19. In addition, blood plasma could possibly be used in individuals with disease to minimize clinical manifestations and death-rate.

My perspective agrees with the viewpoint of Casadevall and Pirofski who reported that an individual who is ill with COVID-19 and recuperated presented top calibers of equalizing antibody, serum carrying these antibodies can be given in a preventive style to prohibit contagion in top-hazard patients. Also, convalescent serum could possibly be utilized in persons with clinical illness to minimize illnesses and death-rate. Their point of view debates that human convalescent serum is a choice for preventing and therapy of COVID-19 sickness that could be quickly ready during the time that there are enough numerals of individuals who have recuperated and can give the serum [12].

In conclusion, there is a hope that my proposed plasma-derived therapy could shed light on a promising remedy. The treatment might be an ideal choice to be used or combined with other immune modulating agents. The doctors considered using CP therapy because Covid-19 has been shown in some studies to cause severe damage to the lungs, liver and other organs. By using this suggested technique, I expect to use the antibodies created by recovered cases as a succeeded therapy for novel sick persons, with the target of consolidation their immune systems and decreasing the riskiness of symptoms connected with the new virus. Well known that Patients who have retrieved from an illness have persistent antibodies produced by the impregnable system swimming in their plasma. Highly active immune globulin focuses the antibodies in a recuperated sick person. I am ultimately may provide the novel preys immune system an excess of antibodies to optimistically gain them during the very highly severe stage. Blood-derived plasma could supply my premier-line protection for Covid-19 patients, particularly those one who are elderly and in a lot big danger for problems. The effectiveness of this method is unbeknown, but historic expertise proposed that CP may be most efficient in forbidding malady than in the cure of affirmed disease. The remedy is not envisaged as an elixir to curing coronavirus, but may be an interim stage that could aid until availability of sturdy selections such as vaccines. Such method is merit attempting. I would pick up novel science from such disaster.

My recommendations are made for providing treatment centers (Local and International) in the isolation hospitals with simple equipped lab to implement my hypothesized therapeutic method. My perspetive presenting details of my optimized precise method of preparation of CP has to be spread locally and globally to all treatment centers in the isolation hospitals.

Bibliography

1. WHO (Updated 17 March 2020). Rolling updates on coronavirus disease (COVID-19).
2. Montaser, L. M. & Fawzy, S. M. (2014). Promising cell therapy achieves improvement outcomes. -Presented at: Int Society for Experimental Hematology (ISEH) 43 Annual Scientific Meeting 21-24. Montreal, Canada. Experimental Hematology, 42(8), S53-53.
3. Montaser, L. M., Abbassy, H. A. & Fawzy, S. M. (2016-b). Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with Nano scaffolds. Proc. SPIE 9930, 99300V, San Diego, CA, USA.
4. Montaser, L. M. (2016). Editorial: Regenerative Medicine & Tissue Engineering-Driven Innovation of Medical Science and Technology. Adv Tissue Eng Regen Med Open Access, 1(1), 1-2.
5. Montaser, L. M., Eid, T. A., Helwa, M. A. & Mesregah, M. K. (2017). Application of PRP preparation rich in growth factors in knee osteoarthritis. Men Med J (MMJ)., 30(1), 139-146.
6. Montaser, L. M. (2018). Editorial, Outcomes of technology’s epic success stories in the field of regenerative medicine and tissue engineering. Adv Tissue Eng Regen Med., 4(4), 100-101.
7. Chen, S. (2020). Coronavirus far more likely than Sars to bond to human cells due to HIV-like mutation, scientists say.
8. Pearce, K. (2020). Infusions of antibody-laden blood have been used with reported success in prior outbreaks, including the SARS epidemic and the 1918 flu pandemic.
9. Harper, M. & Feuerstein, A. (2020). How blood plasma from recovered patients could help treat the new coronavirus.
10. PM Group Worldwide (2020). Takeda begins development of COVID-19 plasma therapy.
11. Casadevall, A. & Pirofski, L. (2020). The convalescent sera option for containing COVID-19. J Clin Invest., 1-5.

Biography

Laila Mahmoud Montaser MD was born in the City of Alexandria, Egypt, in a family of dynasty doctors, graduated from Faculty of Medicine, Alexandria University and got Diploma degree in Microbiology from Alexandria University, Diploma degree in Clinical Pathology, and MD from Faculty of Medicine, Tanta University. Prof Montaser is a Professor in Clinical Pathology; Chair of Stem Cell, Regenerative Medicine, Nano medicine and Tissue Engineering (SRNT) Research Group. She served as the Founder of Clinical Pathology Department Faculty of Medicine, Menoufia University, Egypt, was being the Chair of Department of Clinical Pathology for more than 10 years. She supervised more than 44 M. Sc. theses and 13 Doctorate theses. She has made Faculty of Medicine a hub at Menoufia University. She is uniquely trained and situated and has a philosophy on how to manage research and has written numerous abstracts and research papers on Clinical Pathology, Hematology, and also Stem Cell, Regenerative Medicine, Nano Medicine and Tissue Engineering, her research interest, published in top international journals and Conferences. She has an important intellectual property (IP) on the proposal of a national project to launch an innovative strategy by integration of novel education method (Entrepreneurship Education) in the educational system in Egypt focus on the preparation of youth to meet the requirements of the labor market and develop a plan to implement the education needs associated with the labor market. She is a member of several international and national societies. She is an Honorable Editorial Board Member/Peer Reviewer for many National and International Journals. Montaser’s distinguished career as a Prof, and researcher who had an enormous international impact selected her for three times at 1986, 1998, and 2002 by Council of Menoufia University to Award of “Ideal Doctor” from Egyptian Medical Syndicate and also nominated to two major awards: TWAS prize in Medical Sciences and Nano Science Research Excellence due to her scientific achievements worldwide.

Email: lailamontaser@gmail.com