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 Table of Contents  
SHORT ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 209-211

COVID-19 convalescent plasma product: Harvesting plasma from single unit whole blood, a cost effective alternative to plasmapheresis


Lok Samarpan Regional Blood Center, Surat, Gujarat, India

Date of Submission11-Jul-2020
Date of Decision23-Jul-2020
Date of Acceptance30-Jul-2020
Date of Web Publication31-Jul-2020

Correspondence Address:
Dr. Sanmukh R Joshi
Lok Samarpan Regional Blood Center, Surat, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_66_20

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  Abstract 


The COVID-19 pandemic has affected people from almost all parts of the world. There is no specific pharmaceutical drug available. So also, there is no vaccine developed as yet. In the circumstance, the passive immunity imparted by the preformed antibody in the plasma from the convalescing patient could be a useful approach. COVID-19 convalescent plasma (CCP) can be collected by an automated apheresis device. However, the preparation becomes expensive, and average blood banks cannot afford to establish infrastructure in terms of machine and material requirements. The recommended dose of 200 mL of CCP for the treatment of a patient can easily be met from a single whole blood unit by any blood bank with the facility of blood component separation. This approach can significantly reduce the cost of the treatment to the patient with COVID-19.

Keywords: Convalescent plasma therapy, COVID-19 pandemic, plasma from single unit whole blood, plasma separation through apheresis device


How to cite this article:
Joshi SR. COVID-19 convalescent plasma product: Harvesting plasma from single unit whole blood, a cost effective alternative to plasmapheresis. Glob J Transfus Med 2020;5:209-11

How to cite this URL:
Joshi SR. COVID-19 convalescent plasma product: Harvesting plasma from single unit whole blood, a cost effective alternative to plasmapheresis. Glob J Transfus Med [serial online] 2020 [cited 2020 Nov 26];5:209-11. Available from: https://www.gjtmonline.com/text.asp?2020/5/2/209/291243



The severe acute respiratory syndrome (SARS)-CoV-2 virus causing the COVID-19 pandemic infection has affected one and all across the world halting most human activities. The infection has proved to be a killer disease with mortality and more importantly mortality of alarming proportions. This has paralyzed the health services as well as the economy of the world.

Supportive care, like oxygenation through a ventilator, helps critical patients to alleviate symptoms. However, there is neither specific pharmacological medication available nor any vaccine for the moment to treat the victim or protect an individual from the infection. Living in isolation remains the only effective measure to get guarded against this dreaded disease. Man is a social animal and tends to breach the norms laid down by the authority to remain isolated. The vulnerable people are those with poor health status, the elderly, the pregnant, and the others having underlying ailments such as diabetes or cardiac anomalies. Special care should be taken by the people in this category to avoid exposure to the infection.

Before the era of the antibiotics, the convalescent plasma obtained from the patients recovered of certain infections was used to treat the patient with corresponding active infection. In the recent past, the convalescent plasma has shown desirable results against several coronaviruses as the cause for the SARS, the Middle East respiratory syndrome, and H1N1 influenza.[1],[2],[3]

As of now, there is neither a specific drug nor a vaccine available that can treat or protect a person from the COVID-19. The use of the convalescent plasma, collected from the patients who have recovered from the COVID-19 infection, could be a potential therapy for the disease. It was experimentally demonstrated ex vivo that the serum from a convalescent patient may neutralize and prevent the viral entry into the study cell lines;[4],[5] Bloch et al.[6] have provided empirical evidence on the benefit of COVID-19 convalescent plasma (CCP) as a treatment for the patient with COVID-19. It was shown that during the postrecovery period between the 14th and the 28th day, the patients may have the presence of enough amounts of the neutralizing antibodies developed against the COVID-19 virus. The CCP obtained from such individuals and infused to other patients with infection during the active phase may impart passive immunity to yield a rapid recovery from the disease. A clinical trial on a small number of critically ill patients with COVID-19 showed significant improvement in their clinical status.[7],[8] However, the authors felt that the precise effect of CCP cannot be ascertained as these small numbers of participants were also receiving concurrent experimental antiviral drugs. Duan et al.[9] have explicitly shown the effectiveness of the CCP therapy in severe COVID-19 patients in addition to other supportive treatment.

The confidence among the stakeholders was momentarily shaken when a report came from South Korea[10] showing that the patients recovered from COVID-19 were found positive for the infection on repeat testing for the virus using molecular methods. It had undermined the immunity developed through the exposure of virus and implied that the patients could catch the infection in spite of having recovered from the disease and that the antibody developed through active immunization was no longer protective. However, the detailed investigations revealed that the positive result on the molecular study was not due to re-infection, rather was due to the lingering particles of the virus already present.

In India, like other centers in the World, we are in the experimenting phase in the use of CCP product for its efficacy to curb the infection. Limited centers are permitted by the authorities to conduct the trial. Once approved, the CCP product could be allowed to be used as the line of treatment in the COVID-19 infection. The CCP is collected through the automated plasmapheresis device from the recovered patient and used to treat patients in the recommended therapeutic dose of 200 mL plasma for each of the patients. It is an irony that the preparation of CCP may not be feasible at an average district level blood bank. Having the apheresis machine installed at every blood bank may impose an enormous financial burden (approximate cost of ₹30,00000 per machine) on an average blood bank setup in the country. If one enters into the reagent-rent contract with the supplier of the reagent kits, the machine may be installed free, but the cost of the kit may still be prohibitive for the collection of 2 × 200 mL of plasma (cost, ₹15000 per kit).

At the smaller blood banks, with basic blood component separation facility, one can easily collect the 200 mL quantity of the CCP from a single unit blood donation from a COVID-19 recovered donor in an economical manner with approximate cost of ₹1500. The blood unit can be collected in the double-bag system as usual, and the CCP is separated using the refrigerated centrifuge. Even at a place where the refrigerated centrifuge is not available, one can go with the makeshift arrangement of keeping the blood bag in erect position overnight under refrigeration, during which the red cells may settle down through natural gravitation. The supernatant plasma is transferred to the satellite bag prelabeled as the single donation CPP. The RBCs from the mother bag may be reintroduced to its donor as an autologous transfusion or may be used for non-COVID-19 recipients who require an allogeneic red cell transfusion. Repeat collections by the leapfrog approach after a week or thereafter may also be considered if more plasma is to be harvested.

The WB donation has certain advantage as to the donor may easily be convinced for donation for the amount of blood collected and in limited time of 15 min or so that is certainly less than 1½ h required for plasmapheresis.

CCP treatment is aimed to impart passive immunity to the patient who is in active phase of the COVID-19. The basis of using the CCP is to provide antibody present in patient after recovery from the disease. Some recovered patients may have apprehension that donation will lead to reduction in antibody titer. However, the feedback physiological mechanism is expected to trigger production or more antibodies. This phenomenon was observed among the regular repeat blood donors having a high titer of the ABO-isoantibody.[11] Thus, it is likely that the level of antibody may not fall, rather raise upon repeated blood donations

The titer of the immunoglobulin G (IgG) antibody in the CCP plasma also matters to its efficacy for the treatment and required guidelines continue to be evolved. We, in our country, have certain challenges to meet these criteria laid down by the authorities that require amendment. We still need to have appropriate reagents and equipment to check the titer in the collected plasma. The minimum requirement of 1:640 titer in CCP, based on limited studies in China, may not hold good in every convalescing donor. The optimum titre of CCP needs to be looked at again and in the absence of a validated method, the therapy must not be denied. The CCP with a high titer IgG antibody may also show variable success rate in treatment. The very fact that the patient recovered from active disease shows that the antibody titre he developed was adequate to cure or it could also mean that there are other mechanism at play in addition to humoral immunity, may be T cell mediated immunity. The recovered patient with a low titer antibody may indicate that it is not the humoral immunity alone but some other complementary mechanisms, like the cell-mediated immunity, with the result, the disease is controlled through the natural course of the infection. Whole blood with a cellular portion rather than the separated plasma from the recovered patient may be more effective even with a low titer antibody. However, this aspect should be explored further to understand the protective mechanisms of blood transfusion therapy in COVID-19. The authorities should keep this point in mind while formulating the policy.

CCP collected through apheresis procedure may give a better yield to cater to more than one patient. Furthermore, the same person may donate at shorter interval and more frequently for the purpose. As against that, the CCP plasma harvested from a single donation of whole blood (SDWBCCP) may serve a single patient with the quantity of the plasma obtained. Besides, such donor can donate again after a long interval of 3 months unless the RBCs are reintroduced to the donor after the donation, However, SDWBCCP has its own value as to make it possible to fight COVID-19 at every nook and corner of the country like India for its simplicity and not requiring sophisticated infrastructure and cost-effective structure.

High-quality research on the matter concerning the health issues is of importance on its own merit and that can be tackled later. It is more important to offer a harmless therapy like CCP when the pandemic is on and the shadow of death lurks on the victims who want to survive by every means. The therapy is safe as envisaged by the research group at Mayo Clinic and collaborators in tandem with the Food and Drug Administration's National Expanded Access Program for COVID-19, USA.[12]

While blood banks should be prepared to supply convalescent blood products from the patients cured from the COVID-19, the list of such prospective donors should be provided by the appropriate authorities to perform the procedure to collect the blood products.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005;24:44-6.  Back to cited text no. 1
    
2.
Ko, JH, Seok H, Cho SY, Ha YE, Baek JY, Kim SH, et al. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: A single centre experience. Antivir Ther 2018;23:617-22.  Back to cited text no. 2
    
3.
Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 2011;52:447-56.  Back to cited text no. 3
    
4.
Hoffmann M, Kleine-Weber H, Krüger N, Müller M, Drosten C, Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. Biorxiv. 2020.[Doi: 10.1101/2020.01.31.929042].  Back to cited text no. 4
    
5.
Wu Y, Wang F, Shen C, Peng W, Li D, Zhao C, et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science 2020;368:1274-8.  Back to cited text no. 5
    
6.
Bloch EM, Shoham S, Casadevall A, Sachais BS, Shaz B, Winters JL, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest 2020;130:2757-65.  Back to cited text no. 6
    
7.
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;323:1582–9. doi:10.1001/jama.2020.4783  Back to cited text no. 7
    
8.
Ye M, Fu D, Ren Y, Wang F, Wang D, Zhang F, et al. Treatment with convalescent plasma for COVID-19 patients in Wuhan, China [published online ahead of print, 2020 Apr 15]. J Med Virol. 2020;10.1002/jmv.25882. doi:10.1002/jmv.25882  Back to cited text no. 8
    
9.
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;117:9490-6.  Back to cited text no. 9
    
10.
Korean Centers for Disease Control. News Room. Available from: https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030. [Last accessed on 2020 Jul 30].  Back to cited text no. 10
    
11.
Shanbhag SR, Joshi SR, Bhatia HM. Evaluation of the two screening techniques in the detection of high titre anti-A and anti-B. J Med Res 1973;61:1824-30. PMID: 4787038.  Back to cited text no. 11
    
12.
Nellis R. Early indicators: Investigational convalescent plasma is safe for patients with COVID19. Mayo Clinic News Network May 14, 2020. Available from: https://newsnetwork.mayoclinic.org/discussion/early-indicators- investigational-convalescent-plasma-is-safe-for-patients-with- covid-19. [Last accessed on 2020 Jul 15].  Back to cited text no. 12
    




 

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