Convalescent plasma and hyperimmune globulin therapy in COVID-19

Figures & data

Figure 1. Immunoglobulin, hyperimmunoglobulin and convalescent plasma preparation

Table 1. Comparison of the convalescent plasma and hyperimmune globulin therapies

	Convalescent Plasma (CP)	Hyperimmune globulin (HIG)
Infusion volume	More	Less
Neutralizing antibody titer	Low (1/80-1/160)	High (1/640 vs)
Antibody amount	Not standard	Standard
Polyclonal neutralizing antibodies for microorganisms	Yes	Yes
ABO and Rh compatibility	Required	Not required
Pooling to process period (convalescence, screening, apheresis, etc.)	Relatively short (<6 weeks)	Relatively long (>6 months)
Fractionation and pathogen inactivation steps	Absent	Present
Safety concerns (Allergic and anaphylactic reactions, TRALI, TACO, etc.)	Higher	Lower
Complement proteins, antimicrobial peptides, and other antibodies	Generally included	Generally not included
The likelihood of transfer of strain-specific neutralizing antibodies *	More	Less
The risk of autoantibody^# transfer	More	Less
Cost	Less	More
* Alteration in the viral gene is less important due to the increased chance of pooling from donors with proximity ^# Exclusion criteria for donors due to the risk of autoantibody transfer: Female donors who have been pregnant before, donors having autoimmunity, and male donors in their late adulthood. The autoantibodies may be against immune response elements, such as interferon, or Human leukocyte antigens (HLA).

Table 2. Randomized controlled studies using convalescent plasma therapy in patients with SARS-CoV-2

Authors	Trial	Number of Patients treated	Major Outcome	Adverse Effect
Duan K et al. [9]	Effectiveness of convalescent plasma therapy in severe COVID-19 patients	10 severe patients, 10 controls	Viremia resolved in seven patients having viremia	No serious adverse event
Li L et al. [4]	Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening covid-19 a randomized clinical trial	52 patient, 51 controls	Clinical Improvement within 28 days	Chills and rashes within 2 hours of transfusion (n = 1), shortness of breath, cyanosis, and severe dyspnea within 6 hours of transfusion (n = 1)
Liu et al. [5]	Convalescent plasma treatment of severe COVID-19: A matched control study	39 hospitalized patients with severe to life-threatening COVID-19, control (n = ?)	Improvements in their supplemental oxygen requirements, improved survival	-
Agarwal A et al. [3]	Convalescent plasma in the management of moderate COVID-19 in adults in India: open label phase II multicentre randomized controlled trial (PLACID trial)	235 patients, 229 controls	Earlier resolution of shortness of breath and fatigue and higher negative conversion of SARS-CoV-2 RNA on day 7 of enrollment	Pain at the infusion site, chills, nausea, bradycardia, and dizziness (n = 1), fever and tachycardia (n = 3), dyspnea (n = 2), blockage of an intravenous catheter (n = 2), mortality possibly related to convalescent plasma transfusion (n = 3)
Salazar et al. [7]	Treatment of Coronavirus Disease 2019 Patients with Convalescent Plasma Reveals a Signal of Significantly DecreasedMortality	316 patients, 251 controls	A reduction in mortality within 28 days, specifically in patients transfused within 72 hours of admission with plasma	Minimal adverse effects
Libster R et al. [8]	Early high-titer plasma therapy to prevent severe COVID-19 in older adults.	80 old adult patients, 80 controls	Decrease in progression of COVID-19	-
Simonovich et al. [6]	A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia	228 patients, 105 controls	No significant difference in the clinical status and overall mortality	Nonhemolytic febrile reactions (n = 5)
Abolghasemi H et al. [44]	Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study	115 patients, 74 controls	Lower intubation need and length of hospital stay	-
Shenoy AG et al. [48]	Early mortality benefit with COVID-19 convalescent plasma: a matched control study	263 patients, 263 controls	A decreased risk of death at 7 and 14 days, but not 28 days after transfusion	-

Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Nat Acad Sci. 2020;117:9490–9496.

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Li L, Zhang W, Hu Y, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. Jama. 2020;324:460–470.

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Liu ST, Lin H-M, Baine I, et al. Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study. Nat Med. 2020 Nov;26(11):1708-1713.

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Agarwal A, Mukherjee A, Kumar G, et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). bmj 2020;371:m3939.

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Salazar E, Christensen PA, Graviss EA, et al. Treatment of coronavirus disease 2019 patients with convalescent plasma reveals a signal of significantly decreased mortality. Am J Pathol. 2020;190:2290–2303.

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Libster R, Pérez Marc G, Wappner D, et al. Early high-titer plasma therapy to prevent severe covid-19 in older adults. N Engl J Med. 2021;384:610–618.

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Simonovich VA, Burgos Pratx LD, Scibona P, et al. A randomized trial of convalescent plasma in Covid-19 severe pneumonia. N Engl J Med. 2021;384:619-629.

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Abolghasemi H, Eshghi P, Cheraghali AM, et al. Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: results of a multicenter clinical study. Transfus Apher Sci. 2020;15:102875.

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Shenoy AG, Hettinger AZ, Fernandez SJ, et al.Early mortality benefit with COVID-19 convalescent plasma: a matched control study. Br J Haematol. 2021;192:706–713.

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