Use of convalescent plasma to treat COVID-19: case studies

Beneti, Stéphani Caroline; Marques, Leila Larisa Medeiros; Mattos, Gisely; Cardoso, Flávia Aparecida Reitz

doi:10.1590/1519-6984.262897

Stéphani Caroline Beneti

Universidade Tecnológica Federal do Paraná - UTFPR, Departamento Acadêmico de Alimentos e Engenharia Química, Campo Mourão, PR, Brasil

http://orcid.org/0000-0001-7888-5820

Leila Larisa Medeiros Marques

Universidade Tecnológica Federal do Paraná - UTFPR, Departamento Acadêmico de Alimentos e Engenharia Química, Campo Mourão, PR, Brasil

http://orcid.org/0000-0002-5024-0542

Gisely Mattos

Universidade Tecnológica Federal do Paraná - UTFPR, Programa de Pós-graduação em Inovações Tecnológicas - PPGIT, Campo Mourão, PR, Brasil

http://orcid.org/0000-0002-9405-4637

Flávia Aparecida Reitz Cardoso ^**e-mail: reitz@utfpr.edu.br

Universidade Tecnológica Federal do Paraná - UTFPR, Programa de Pós-graduação em Inovações Tecnológicas - PPGIT, Campo Mourão, PR, Brasil

Universidade Tecnológica Federal do Paraná - UTFPR, Programa de Pós-graduação em Tecnologia de Alimentos - PPGTA, Campo Mourão, PR, Brasil

http://orcid.org/0000-0002-0432-9191

*e-mail: reitz@utfpr.edu.br

Figures (2)
Tables (3)

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Figure 1
Scheme for using convalescent plasma for COVID-19. An individual who has had COVID-19 and has recovered has their blood drawn and screened for virus neutralizing antibodies. Once identified, high levels of virus neutralizing antibodies can be administered prophylactically to prevent infections in high-risk cases in vulnerable individuals with underlying medical conditions, healthcare professionals and individuals with exposure to confirmed COVID-19 cases. In addition, convalescent serum can potentially be used in individuals with clinical illness to reduce symptoms and mortality. The effectiveness of this approach is not known, but historical experience suggests that convalescent sera may be more effective in preventing disease than in treating established disease. Source: Casadevall and Pirofski (2020)CASADEVALL, A. and PIROFSKI, L., 2020. The convalescent sera option for containing COVID-19. The Journal of Clinical Investigation, vol. 130, no. 4, pp. 1545-1548. http://dx.doi.org/10.1172/JCI138003. PMid:32167489.
http://dx.doi.org/10.1172/JCI138003... .

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Figure 2
Changes in IgG and IgM ELISA specific for the receptor-binding domain and neutralizing antibody titers before and after convalescent plasma transfusion in patients. Source: Shen et al. (2020)SHEN, C., WANG, Z., ZHAO, F., YANG, Y., LI, J., YUAN, J., WANG, F., LI, D., YANG, M., XING, L., WEI, J., XIAO, H., YANG, Y., QU, J., QING, L., CHEN, L., XU, Z., PENG, L., LI, Y., ZHENG, H., CHEN, F., HUANG, K., JIANG, Y., LIU, D., ZHANG, Z., LIU, Y. and LIU, L., 2020. Treatment of 5 critically Ill patients with COVID-19 with convalescent plasma. Journal of the American Medical Association, vol. 323, no. 16, pp. 1582-1589. http://dx.doi.org/10.1001/jama.2020.4783. PMid:32219428.
http://dx.doi.org/10.1001/jama.2020.4783... .

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Table 1
Performance of different detections in samples at different times since the onset of disease in patients.

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Table 2
Clinical characteristics of patients infected with SARS-CoV-2 who received convalescent plasma.

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Table 3
Comparison of viral load, clinical indices and laboratory results before and after transfusion with convalescent plasma.

Days after onset		RNA		Ab		IgM		IgG		RNA+Ab
	n		Sensitivity		Sensitivity		Sensitivity		Sensitivity		Sensitivity
		n(+)		n(+)		n(+)		n(+)		n(+)
			(%, 95%Cl)		(%, 95%Cl)		(%, 95%Cl)		(%, 95%Cl)		(%, 95%Cl)
			67.1		93.1		82.7		64.7		99.4
Total	173	112^$		161		143		112		172
			(59.4, 74.1)		(88.2, 96.4)		(76.2, 88		(57.1, 71.8)		(96.9, 100.0)
			66.7		38.3		28.7		19.1		78.7
1-7	94	58^$		36		27		18		74
			(55.7, 76.4)		(28.5, 48.9)		(19.9, 39.0)		(11.8, 28.6)		(69.1, 86.5)
			54.0		89.6		73.3		54.1		97.0
8-14	135	67^$		121		99		73		131
			(44.8, 63.0)		(83.2, 94.2)		(65.0, 80.6)		(45.3, 62.7)		(92.6, 99.2)
			45.5		100.0		94.3		79.8		100.0
15-39	90	25(		90		83^* * Two patients missed IgM tests due to inadequate plasma samples;		71^# # One patient missed IgB tests due to inadequate plasma samples;		90
			(32.0, 59.5)		(96.0, 100.0)		(87.2, 98.1)		(69.9, 87.6)		(96.0, 100.0)

	Patient
	1	2	3	4	5
Sex	Male	Male	Female	Female	Male
Age, y	70s	60s	50s	30s	60s
Weight, kg	55	85	60	41.5	87
Smoking	No	No	No	No	No
Blood type	B	B	B	A	B
Coexisting chronic diseases	None	Hypertension; mitral insufficiency	None	None	None
Disease presentation and course
Estimated incubation period, d^a a Estimated incubation period defined as interval between estimated exposure to SARS-CoV-2 and symptom onset.	1	7	3	7	15
Interval between symptom onset and admission, d	2	4	2	3	2
Interval between admission and plasma transfusion, d	22	10	20	3	2
Complications prior to plasma transfusion	Bacterial pneumonia; severe ARDS; MODS	Bacterial pneumonia; fungal pneumonia; severe ARDS; myocardial damage	Severe ARDS	Severe ARDS	Severe ARDS
Most severe disease classification	Critical	Critical	Critical	Critical	Critical
Treatments
Steroids	Methylprednisolone	Methylprednisolone	Methylprednisolone	Methylprednisolone	Methylprednisolone
Antivirais	Lopinavir/ritoavir; interferon alfa-1b; favipiravir	Lopinavir/ritoavir; arbidol; darunavir	Lopinavir/ritoavir; interferon alfa-1b	Interferon alfa-1b; favipiravir	Lopinavir/ritoavir; interferon alfa-1b

		Patient
		1		2		3		4		5
Clinical characteristics
Body temperature, °C
Just before transfusion		38.6		39.0		37.6		38.3		39.0
Day 1 posttransfusion		38.5		36.8		37.7		37.9		39.0
Day 3 posttransfusion		38.1		36.6		37.0		36.6		36.8
Day 7 posttransfusion		37.8		37.2		36.5		37.9		36.8
Day 12 posttransfusion		37.0		36.8		36.6		36.8		37.9
SOFA score^a
Just before transfusion		5		10		3		3		2
Day 1 posttransfusion		4		12		4		3		2
Day 3 posttransfusion		6		10		3		2		2
Day 5 posttransfusion		5		11		2		2		2
Day 7 posttransfusion		3		7		2		2		1
Day 12 posttransfusion		2		4		2		1		1
P_AO2/F_IO2^b b PAO2/FIO2 ratio was defined as the ratio of the partial pressure of arterial oxygen to the percentage of inspired oxygen.
Just before transfusion		276		209		172		188		205
Day 1 posttransfusion		300		134		184		242		292
Day 3 posttransfusion		220		230		164		233		304
Day 7 posttransfusion		245		206		220		290		230
Day 12 posttransfusion		284		316		342		322		366
Ct value^c c Cycle thresshold is the number of polymerase chain reaction cycles required for gene amplification. A higher Ct value is correlated with a lower viral load. Lowest value (highest viral load) between hospital admission and plasma transfusion; (viral load proxy)
On admission to hospital		23.0		19.7		18.9		38.0		28.0
Lowest value during hospitalization^d (highest viral load)	19.2		19.7		18.9		26.6		26.5
Just before transfusion	28.5		22.0		33.0		26.6		35.9
Day 1 posttransfusion	30.0		23.7		38.5		28.0		Negative
Day 3 posttransfusion	34.4		25.0		Negative		Negative		Negative
Day 7 posttransfusion	38.0		32.0		Negative		Negative		Negative
Day 12 posttransfusion	Negative		Negative		Negative		Negative		Negative
Mechanical ventilation
Onset, days before transfusion		11		2		12		9		2
Extubated, days posttransfusion		Intubated		Intubated		2		9		9
ECMO
Onset, days before transfusion		Not received		1		Not received		Not received		Not received
Removal, days posttransfusion		NA		5		NA		NA		NA
Laboratory findings
C-reactive protein, mg/L (normal range, <8)
Before transfusion		163.4		242.8		65		156.0		173.1
Day 1 posttransfusion		146.2		223.0		108.3		NT		186.8
Day 3 posttransfusion		115.1		75.2		78.7		160.8		233.7
Day 5 posttransfusion		31.3		10.4		74.7		NT		260.4
Day 7 posttransfusion		31.2		13.9		6.2		9.6		5.5
Day 12 posttransfusion		5.3		33.1		NT		5.8		3.2
Procalcitonin, ng/mL (normal range, <0.1)
Before transfusion		1.2		7.3		0.1		0.2		0.2
Day 1 posttransfusion		1.3		19.7		0.1		0.08		0.4
Day 3 posttransfusion		1.6		13.9		0.09		0.07		1.5
Day 5 posttransfusion		0.9		1.8		0.08		NT		0.9
Day 7 posttransfusion		1.1		0.1		0.04		0.04		0.09
Day 12 posttransfusion		0.4		0.2		NT		0.04		0.07
IL-6, pg/mL (normal range, 0-7)
Before transfusion		70.5		438.2		63.9		79.1		87.8
Day 1 posttransfusion		74.9		NT		118.5		39.3		NT
Day 3 posttransfusion		34.5		1045.0		67.0		25.8		797.9
Day 5 posttransfusion		24.1		334.1		590.5		NT		NT
Day 7 posttransfusion		30.8		29.8		174.3		34.0		69.9
Day 12 posttransfusion		6.1		31.8		NT		2.7		54.9
Length of hospital stay^d		Remains hospitalized		Remains hospitalized		53		51		55
Current status as of March 25, 2020		Stable, still received mechanical ventilation		Stable, still received mechanical ventilation		Discharged home		Discharged home		Discharged home

[1] *e-mail: reitz@utfpr.edu.br

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Use of convalescent plasma to treat COVID-19: case studies

Uso de plasma convalescente para tratar COVID-19: estudos de caso

Abstract