Ali A, et al., Journal of Ideas in Health 2020;3(4):254-257 © The Author(s). 2020 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. e ISSN: 2645-9248 Journal homepage: www.jidhealth.com Open Access To which extent a convalescent plasma therapy could be a benefit for COVID-19 patients? Abdelmonem Ali1, Ahmed Abuelhassan1, Ebtehal Fawzi1, Alfatih Aboalbasher2, Sheima Elbasheer3, Nagia Suliman4*, Alaa Elhussein5, Mayada Ali6 Abstract The emergence of an unprecedented pandemic SARS-COV-2 caused perplexed in the medical community because of a high infection rate and rising mortality among COVID-19 patients. Till now, there is no particular treatment for the disease; nevertheless, there is an extensive effort from scientists to find out an immediate therapeutic plan to show how to deal with the current situation. One of the solutions currently presented is Convalescence plasma (CP). Through this narrative review, we will shed light on CP's efficiency as a therapeutic agent for COVID-19, especially there is no proven vaccine or antiviral available up to date. CP could be considered one of the therapeutic approaches, but some limitations are still considered before it is established as a therapeutic agent. Along with evaluating CP from blood donors, the plasma companies could take future steps by manufacturing a target dose of globulins that contain standardized antibody, to reach the terms of health setting administering therapy. Keywords: Convalescence plasma, COVID-19, Transfusion, Neutralizing Antibodies, Sudan Background In the time of COVID-19, where coronavirus disease has spread Severe respiratory distress symptoms caused by SARS-CoV-2 are considered a newly emerged beta coronavirus responsible for COVID-19. It was first reported in Wuhan, China, in December 2019, when around 81 767 cases with 3281 deaths have been recorded [1]. Later in March, the WHO proclaimed COVID-19 a pandemic disease when it appeared in approximately 195 countries [2]. The mechanism of the pathogenesis of COVID-19 infection has not been fully clarified [3]. There is no proven vaccine or therapy for COVID-19 until now. The disease's clinical management protocol recommended by WHO focuses on infection prevention, monitoring, and detection [4]. Despite the continued lack of accuracy and transparency about the COVID-19, scientists are still trying to figure out ideal strategies to develop a treatment for COVID-19. One of the promising strategies is Convalescent Plasma Therapy (CPT). Up to date, using CPT for COVID-9 patients has been demonstrated in multiple studies to reduce the mortality rate in this unprecedented pandemic situation. The investigators in these studies relied on the fact that the CPT is not a new technique, its efficacy and safety had already been tested in other causative agents similar to SARS-CoV-2, despite the presence of a few difference between SARS-CoV-2 and other types of coronavirus, but the mechanism of CP could be the same. [5,6,7]. The issue of using the convalescent plasma has grown in importance in light of pandemic COVID-19, especially in the absence of availability of vaccine or other treatment, so in the current review, we will attempts to discuss the desired benefits and some limitation of CPT. Previous utilization of convalescent plasma Convalescent plasma (CP) therapy is known for a long time and was used for many viral and bacterial diseases. Previously CP used to treat patients with various viral infections, such as treating the Spanish flu in 1918, H1N1 infection in 2009, Ebola patients in 2014, and Middle East Respiratory Syndrome (MERS) in 2015 [8,9,10]. Thereby, CP was suggested as one of the therapeutic options for COVID‐19 patients [11]. The CPT mechanism is based on plasma transfusion from recovered individuals (Who are harmful to COVID‐19) to patients with COVID-19 [12,13]. This transfusion is considered as a type of passive immunity, whereas the plasma transfused from patients recovered to patients exposed to the same virus (the plasma contains a Neutralizing Antibodies (NAbs)) (Figure 1) [14,15]. ___________________________________________________ nagiasuliman@hotmail.com 4Department of Clinical Chemistry, College of Medical laboratory science, Al Gezira University, Sudan Full list of author information is available at the end of the article http://www.jidhealth.com/ Ali A, et al., Journal of Ideas in Health (2020); 3(4):254-257 255 This therapy's efficacy has been associated with the concentration of NAbs in plasma from recovered donors [16]. The neutralizing antibodies against SARS-CoV-2 that has been isolated from donors may serve as a promising intervention to SARS-CoV-2 (Figure 2) [17]. Discussion Donors of CP should fulfill the standard eligibility requirements [18], in accordance with the National Guide on Preparation, in addition to following the recommendations from an accredited agency such as WHO. Multiple published studies have discussed CP antibodies' ability to viremia clearance, some of these studies support using CPT for COVID-19, but before starting the process of plasma transfusion, all precaution rules should be applied strictly [19,20]. For instance, Sudan is one of the developing countries that struggle against the spreading of COVID-19. One of the Sudanese studies reported the benefits of using convalescent plasma to treat COVID-19 symptomatic patients. This study has mentioned that specific criteria should be followed for both patient and donor before starting the process of transfusion. One of the CP transfusion criteria from a donor, the donor, should be free from SARS-CoV-2 infection at the time of plasma transfusion. On the other hand, one of the most important CP transfusion criteria to a patient is that the patient should have a clear symptomatic and confirmed diagnosis for COVID-19 depending on the official Sudanese therapeutic protocol for COVID -19. Furthermore, this study recommended using CPT in COVID-19 Sudanese patients at least currently is considered an available costless therapeutic option, especially all other COVID-19 therapeutics alternatives still under investigation studies [21]. Neutralizing antibodies in donor Convalescent sera could be used for critical COVID-19 patients as recommended in one of the previous issues by the Food and Drug Administration [22,23,24]. However, the similarity between some human amino acid sequences with SARS-CoV-2 sequence could unintentionally way induce the autoimmune system [25]. Hence, a rapid vaccination strategy is needed to study interference between viral particles and human molecules to avoid an undesired self-immunity reaction, especially for those who suffer from previous medical history with autoimmune disease. Up to date, a few original practical studies used CPT for COVID-19 patients, but noteworthy still, the validation of the efficacy of CP is a controversial issue between supporters and opponents. Despite this, some reports reveal less hospitalization and a low mortality rate among patients who have been given convalescent plasma [26]. Challenges facing the use of convalescent plasma Dante Mário and his colleagues had mentioned that there are some challenges when we were thinking of using convalescent plasma therapy for COVID -19 patients. Some of these challenges are:- a. Is the convalescent plasma transfusion being more protective if compared with other antiviral treatments? b. Which one is more effective for patients, plasma from donors who have no symptoms or plasma from donors with symptoms? c. What is the best time to transfuse plasma to COVID-19 patients, in other words, early-stage or late-stage? Some previous studies have also mentioned that there are expected complications accompanied by plasma transfusions, such as circulatory overload, anaphylactic reactions, and alloimmunization [27]. These are logical questions that need to be answered before starting accrediting plasma as an acceptable treatment for COVID-19. The current status of therapeutic efforts made with COVID-19 Until the time of writing the current manuscript, the medical Scientists are working day and night to find an effective and suitable vaccine for controlling the deadly COVID-19. Most Vaccine clinical trials platforms are done in developed countries, such as the USA, UK, Germany, Russia, and China. It seems there is an unprecedented race between these countries, which country would be the first one to produce an effective and safe COVID-19 vaccine for the entire world. Instead of racing between vaccine production companies, it would be better if there are information exchange and collaboration to help reach wisdom decision regarding COVID-19 [28]. Global cooperation will help avoid and repeat the mistakes made at the beginning of the COVID-19 crisis due to a lack of information transparency [29]. However, till that time, when the effective and trust vaccine appears and could apply confidently for patients, CPT is Considered an optimal and available option for COVID-19. Ali A, et al., Journal of Ideas in Health (2020); 3(4):254-257 256 Conclusion To sum up, based on the previously published data, the CPT could be an efficient option, at least in the current time, to minimize the morbidity and mortality rate of patients with COVID-19. However, the extreme benefit of using CPT for COVID-19 still needs tremendous investigation. As it is recommended, it would be better if used a well-designed study such as controlled experiments with large sample size. Abbreviation ARDS: Acute Respiratory Distress Syndrome; COVID-19: Corona Virus Disease of 2019; CP: Convalescence Plasma; CPT: Convalescent Plasma Therapy; FDA: Food and Drug Administration; HI1N1: Influenza A virus subtype; MERS: Middle East Respiratory Syndrome; Nabs: Neutralizing Antibodies; SARS: Severe Acute Respiratory Syndrome. Declaration Acknowledgement Our great thanks to the Sudanese Medical Laboratory Technologist in Oman (SMLTO) for their logistic support. Funding The authors received no financial support for their research, authorship, and/or publication of this article. Availability of data and materials Data will be available by emailing nagiasuliman@hotmail.com Authors’ contributions Ahmed Abuelhassan (AA), Ebtehal Fawzi (EF), Alfatih Aboalbasher (AA), Sheima Elbasheer (SE), Nagia Suliman (NS), Alaa El-Hussein (AE), Mayada Ali (MA) have contributed equally to the study concept, design, writing of original draft. Abdelmonem Ali (AA) has reviewed and edited the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate We conducted the research following the Declaration of Helsinki. However, Review Articles need no ethics committee approval. Consent for publication Not applicable Competing interest The author declares that he has no competing interests. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Author details 1Department of Clinical Chemistry, College of Medical laboratory science, Al- Neelain University, Sudan. 2Department of Hematology, College of Medical laboratory science, University of Alzaiem Al Azhari, Sudan. 3Department of Microbiology, College of Medical laboratory science, University of Alzaiem Al Azhari, Sudan. 4Department of Clinical Chemistry, College of Medical laboratory science, Al Gezira University, Sudan. 5Department of Hematology and Immunohematology, Sudan University of Science and Technology, Sudan. 6Department of Medical Microbiology, College of Medical Laboratory Science, Al Gezira University, Sudan. Article Info Received: 10 October 2020 Accepted: 01 November 2020 Published: 24 November 2020 References 1. Owji H, Negahdaripour M, Hajighahramani N. Immunotherapeutic approaches to curtail COVID-19. Int Immunopharmacol. 2020; 88:106924. https://doi.org/10.1016/j.intimp.2020.106924 2. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA.2020;323(16):1582-1589. https://doi.org/10.1001/jama.2020.4783 3. Nagoba B, Gavkare A, Jamadar N, Mumbre S, Selkar S. Positive aspects, negative aspects and limitations of plasma therapy with special reference to COVID-19. J Infect Public Health. 2020 Sep 01. https://doi.org/10.1016/j.jiph.2020.08.011 4. Yılmaz S, Örüç NE, Özcebe OI, Azap A, Çetin AT, Yenicesu I, et al. Regulatory consideration on preparation and clinical use of COVID-19 convalescent plasma. Transfusion and Apheresis Science. 2020;59(5):102846. https://doi.org/10.1016/j.transci.2020.102846 5. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545- 1548. https://doi.org/10.1172/JCI138003 6. Roback JD, Guarner J. Convalescent Plasma to Treat COVID-19: Possibilities and Challenges. JAMA. 2020 Apr 28;323(16):1561- 1562. https://doi.org/10.1001/jama.2020.4940 7. Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. https://doi.org/10.1016/s1473- 3099(20)30141-9 8. Perotti C, Del Fante C, Baldanti F, Franchini M, Percivalle E, Vecchio Nepita E, Seminari E, De Silvestri A, Bruno R, Klersy C. Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol. Intern Emerg Med. 2020 Aug;15(5):819-824. https://doi.org/10.1007/s11739-020-02384-2 9. Abolghasemi H, Eshghi P, Cheraghali AM, Imani Fooladi AA, Bolouki Moghaddam F, Imanizadeh S, et al. Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study. Transfus Apher Sci. 2020; 59(5):102875. https://dx.doi.org/10.1016%2Fj.transci.2020.102875 10. Al-Tawfiq JA, Arabi Y. Convalescent plasma therapy for coronavirus infection: experience from MERS and application in Ali A, et al., Journal of Ideas in Health (2020); 3(4):254-257 257 COVID-19. Hum Vaccin Immunother. 2020 Sep 3:1-7. https://doi.org/10.1080/21645515.2020.1793712 11. Ye M, Fu D, Ren Y, Wang F, Wang D, Zhang F, Xia X, Lv T. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China. J Med Virol. 2020:10.1002/jmv.25882. https://doi.org/10.1002/jmv.25882 12. Syal K. COVID-19: Herd immunity and convalescent plasma transfer therapy. J Med Virol. 2020 Apr 13:10.1002/jmv. 25870. https://doi.org/10.1002/jmv.25870 13. Majbour N, El-Agnaf O. Plasma-derived therapy: can the survivors of COVID-19 help the defenseless? Diagnosis (Berl). 2020 Nov 18;7(4):373-376. https://doi.org/10.1515/dx-2020-0053 14. Kumar S, Sharma V, Priya K. Battle against COVID-19: Efficacy of Convalescent Plasma as an emergency therapy. Am J Emerg Med. 2020 Jun 2: S0735-6757(20)30465-4. https://dx.doi.org/10.1016%2Fj.ajem.2020.05.101 15. Islam A, Rafiq S, Karim S, Laher I, Rashid H. Convalescent plasma therapy in the treatment of COVID-19: Practical considerations: Correspondence. Int J Surg. 2020; 79:204-205. https://doi.org/10.1016/j.ijsu.2020.05.079 16. Zhao Q, He Y. Challenges of Convalescent Plasma Therapy on COVID-19. J Clin Virol. 2020 Jun; 127:104358. https://doi.org/10.1016/j.jcv.2020.104358 17. Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L, et al. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High- Throughput Single-Cell Sequencing of Convalescent Patients’ B Cells. Cell, 2020. 182(1):73-84. e16. https://doi.org/10.1016/j.cell.2020.05.025 18. Epstein J, Burnouf T. Points to consider in the preparation and transfusion of COVID-19 convalescent plasma. Vox Sang. 2020 Aug;115(6):485-487. https://doi.org/10.1111/vox.12939 19. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9490-9496. https://doi.org/10.1073/pnas.2004168117 20. Focosi D, Anderson AO, Tang JW, Tuccori M. Convalescent Plasma Therapy for COVID-19: State of the Art. Clin Microbiol Rev. 2020 Aug 12;33(4): e00072-20: https://doi.org/10.1128/CMR.00072-20 21. Hassan MO, Osman, AA, Abd Elbasit HE, Hassan HE, Rufai H, Satti MMM, et al. Convalescent plasma as a treatment modality for coronavirus disease 2019 in Sudan. Transfusion and Apheresis Science. 2020:102918. https://doi.org/10.1016/j.transci.2020.102918 22. Lee WT, Girardin CG, Dupuis II AP, Kulas KE, Payne AF, et al. neutralizing antibody responses in COVID-19 convalescent sera, The Journal of Infectious Diseases.2020; jiaa673. https://doi.org/10.1093/infdis/jiaa673 23. Han G, Zhou Y-H. Thinking more about therapy with convalescent plasma for COVID-19 patients. Human Vaccines & Immunotherapeutic. 2020. https://doi.org/10.1080/21645515.2020.1787073 24. Franchini M. Why should we use convalescent plasma for COVID-19? Eur J Intern Med. 2020 Jul; 77:150-151. https://doi.org/10.1016/j.ejim.2020.05.019 25. Anand P, Puranik A, Aravamudan M, Venkatakrishnan AJ, Soundararajan V. SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. Elife. 2020 May 26;9: e58603. https://doi.org/10.7554/eLife.58603 26. Joyner MJ, Bruno KA, Klassen SA, Kunze KL, Johnson PW, Lesser ER, et al. Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients. Mayo Clin Proc.2020;95(9):1888- 1897. https://doi.org/10.1016/j.mayocp.2020.06.028 27. Kakaiya R, Campbell-Lee S. Plasma transfusion: current status and future directions. Transfusion. 2012;52 Suppl 1:1S: https://doi.org/10.1111/j.1537-2995.2012.03625.x 28. Katib A. Research ethics challenges during the COVID-19 pandemic: what should and what should not be done. Journal of Ideas in Health2020;3(Special1):185-187. https://doi.org/10.47108/jidhealth.Vol3.IssSpecial1.49 29. Ali Jadoo SA. Was the world ready to face a crisis like COVID- 19? Journal of Ideas in Health2020;3(1):123-4. https://doi.org/10.47108/jidhealth.Vol3.Iss1.45