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DOI: 10.1016/j.htct.2021.03.001
Open Access
Available online 27 March 2021
Suggested guidelines for convalescent plasma therapy for the treatment of COVID-19
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Gil Cunha De Santisa,b, Alfredo Mendronea,c,d, Dante Langhia,e,
Corresponding author
dlanghi@uol.com.br

Corresponding author at: Department of Clinical and Experimental Oncology, Federal University of São Paulo (UNIFESP), Rua Dr. Diogo de Faria, 824 - Vila Clementino, CEP: 5539-7289, São Paulo, SP, Brazil.
, Dimas Tadeu Covasa,b, Antônio Fabrona,f, Afonso José Pereira Corteza,g, Carla Luana Dinardoa,c, Eugênia Maria Amorim Ubialia,b, José Francisco Comenalli Marquesa,h, José Orlando Bordina,e,i, Marilia Alvares Rugania,j
a Associação Brazileira de Hematologia, Hemoterapia e Terapia Celular(ABHH), São Paulo, SP, Brazil
b Hemocentro de Ribeirão Preto, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brazil
c Fundação Pró-Sangue, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
d Hospital Sírio Libanês, São Paulo, SP, Brazil
e Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
f Faculdade de Medicina de Marilia (FAMEMA), Marília, SP, Brazil
g Associação Beneficente de Coleta de Sangue (Colsan), São Paulo, SP, Brazil
h Hemocentro da Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil
i Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil
j Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, RJ, Brazil
Received 04 March 2021. Accepted 13 March 2021
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Table 1. Tests for anti-SARS-CoV-2 antibodies.
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COVID-19 progresses with a heterogeneous clinical course that is mild to moderate in most cases, and severe in approximately 10–15% of patients.

Patients with comorbidities (diabetes mellitus, hypertension, heart disease, obesity, and immunosuppression), in general elderly, can evolve with higher frequency to severe cases of the disease, with severe respiratory failure, requiring intensive care in most cases.

As yet, there is no specific therapy for covid-19. Thus, as an alternative, there is the transfusion of plasma obtained from individuals who are convalescent from covid-19, referred to as convalescent plasma (CP), which contains neutralizing antibodies against SARS-CoV-2O virus.1

The use of CP seeks to passively transfer antibodies to the patient until the affected organism has the time to mount their own immune response.

Observational studies and controlled studies, suggest that CP can be useful, especially units which contain high-titer neutralizing antibodies, with patients presenting a better clinical course.2,3

Recent publications have shown better results with the use of CP in the early days of symptom onset, up to 72 h, before clinical worsening has occurred, as late transfusion seems not to provide clinical benefits.4,5

Most studies used a single dose of PC, ranging from 200 to 500 mL, infused over one or more days.

Altogether, those studies suggest that CP transfusion, containing high-titer neutralizing antibodies, can be of clinical benefit, for specific groups of patients, if administered early.

Potential risks associated with PC transfusion are no greater than those of plasma use in other situations.6 It is worth mentioning, in specific ways, the possibility of circulatory overload risk, especially in elderly patients and in those with renal failure or heart disease, who are less able to tolerate sudden increase in circulating volume and TRALI. For the latter situation, it is considered prudent to use plasma from nulliparous donors, or from donors who had not previously received a hemocomponent transfusion.

Finally, it is determined that the collected CP units contain adequate levels of neutralizing anti-SARS-CoV-2 antibodies. The ideal test for determining these titers is the neutralizing antibody activity test.7 However, this test is labor-intensive, hard-to-perform and scarcely available, and requires a level III biosafety laboratory.

There have been some studies reporting satisfactory results with results obtained by traditional enzyme immunoassay methods, such as Elisa and chemiluminescence, where the intensity of the reading (OD) seems to correlate well with neutralizing antibody titers8,9 (Table 1).

Table 1.

Tests for anti-SARS-CoV-2 antibodies.

Tests Acceptable for Use in the Manufacture of High Titer COVID-19 Convalescent Plasma
Manufacturer (listed alphabetically)  Assay  Qualifying Result 
Abbott  SARS-CoV-2 IgG (ARCHITECT and Alinity i)  Index (S/C) ≥ 4.5 
Beckman Coulter  Access SARS-CoV-2 IgG  S/CO ≥ 3.3 
EUROIMMUN  Anti-SARS-CoV-2 ELISA (IgG)  Ratio ≥ 3.5 
GenScript  cPass SARS-CoV-2 Neutralization Antibody Detection Kit  Inhibition ≥ 68% 
Kantaro  COVID-SeroKlir, Kantaro SemiQuantitative SARSCoV-2 IgG Antibody Kit  Spike ELISA > 47 AU/mL 
Mount Sinai  COVID-19 ELISA IgG  Spike ELISA titer ≥ 1:2880 
Ortho  VITROS Anti-SARSCoV-2 IgG  S/C ≥ 9.5 
Roche  Elecsys Anti-SARSCoV-2  ≥ 132 U/mL 
Siemens  ADVIA Centaur SARS-CoV-2 IgG (COV2G)  Index ≥ 4.8 

Source: Hinton-FDA, 2021.

In summary, consider using CP, in patients with COVID-19, in the situations and ways described below:

  • 1

    Immunosuppressed patients (especially those treated with anti-CD20 monoclonal antibodies).

  • 2

    Elderly patients (≥ 60 years old).

  • 3

    Patients with comorbidities: diabetes mellitus, hypertension, coronary heart disease and obesity.

  • 4

    CP with high-titer neutralizing antibodies (≥ 80), or high DO.

  • 5

    Within 72 h of symptom onset.

Conflicts of interest

The authors declare no conflicts of interest.

References
[1]
A. Casadevall, L.A. Pirofski.
The convalescent sera option for containing COVID-19.
J Clin Invest, 130 (2020), pp. 1545-1548
[2]
Y. Maor, D. Cohen, N. Paran, T. Israely, V. Ezra, O. Axelrod, et al.
Compassionate use of convalescent plasma for treatment of moderate and severe pneumonia in COVID-19 patients and association with IgG antibody levels in donated plasma.
EClinicalMedicine, 26 (2020),
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Convalescent plasma antibody levels and the risk of death from Covid-19.
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Early high-titer plasma therapy to prevent severe Covid-19 in older adults.
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A randomized trial of convalescent plasma in Covid-19 severe pneumonia.
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M.J. Joyner, R.S. Wright, D. Fairweather, J.W. Senefeld, K.A. Bruno, S.A. Klassen, et al.
Safety indicators of COVID-19 convalescent plasma in 5,000 patients.
J Clin Invest, 130 (2020), pp. 4791-4797
[7]
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Longitudinal analysis of clinical serology assay performance and neutralising antibody levels in COVID19 convalescents.
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A. Mendrone-Junior, C.L. Dinardo, S.C. Ferreira, A. Nishya, N.A. Salles, C. de Almeida Neto, et al.
Correlation between SARS-COV-2 antibody screening by immunoassay and neutralizing antibody testing.
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USA. Food and Drug Administration (FDA). Hinton DM The Authorized COVID-19 Convalescent Plasma. Available at: https://www.fda.gov/media/141477/download. [Accessed 26 February 2021].
Copyright © 2021. Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular
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