The assessment of parameters of convalescent plasma and their impact on COVID-19 symptoms

Agnieszka Kuś; Szymon Wieczorek; Jarosław Dybko; Małgorzata Szymczyk-Nużka; Aleksandra Butrym; Krzysztof Dudek; Grzegorz Mazur; Siddarth Agrawal

doi:10.2478/ahem-2025-0006

Figures & Tables

Kaplan-Meier survival curve demonstrating the probability of survival at 28 days post-CP transfusion stratified by age groups (≥ 68 years vs. < 68 years). The log-rank test revealed a significant difference in survival rates (p < 0.001), with younger patients displaying a higher survival probability (97.5% vs. 70.2%)

Kaplan-Meier curves among COVID-19 patients differ by the assessment of the laboratory test results: A) hematocrit level (p = 0.002), B) monocytes level (p = 0.017), and C) pCO2 (p = 0.042) and their associations with survival probability, supported by log-rank tests for statistical significance. V0: baseline (pre-CP transfusion), V1: 3 days post-transfusion, V2: 7 days post-transfusion, V3: 28 days post-transfusion

The distribution of patients differed in leukocyte levels (A) across four visits (pre-CP and three post-CP follow-ups). A significant leukocyte increase is observed (Friedman ANOVA, χ2 = 145.1, p < 0.001). Panel B focuses on hemoglobin levels over the same period, showing progressive normalization (Friedman ANOVA, χ2 = 18.3, p = 0.006). Panels C and D present correlation analyses between leukocyte counts and time post-transfusion, with p-values of < 0.001 and 0.024, respectively. V0 – results directly before the CP administration; V1 – after three days; V2 – after seven days; V3 – after 28 days of CP administration

Patients’ structure differs in assessing the level of inflammation indicators on consecutive days. Panels A and B illustrate CRP levels, with significant declines from baseline to post-CP follow-ups (Friedman ANOVA, χ2 = 145.1, p < 0.001). Panels C and D depict procalcitonin trends, similarly showing reductions (Friedman ANOVA, χ2 = 88.9, p < 0.001). Subpanels include bar graphs with standard deviations and group comparisons via post-hoc tests. Post hoc tests confirmed significant differences between V0 and all subsequent time points for both indicators. V0 – results directly prior the CP administration; V1 – after three days; V2 – after seven days; V3 – after 28 days of CP administration

The results of Friedman tests representing the level of antibodies against: A) IgA – anti - SARS-CoV-2, B) IgM – anti-SARS-CoV-2, and C) IgG – anti-SARS-CoV-2 in the following days of visits (Friedman ANOVA, p < 0.001 for all). Post hoc analysis revealed significant differences between baseline (V0) and 28 days post-CP transfusion (V3) for all antibody types. V0 – results directly prior the CP administration; V1 – after three days; V2 – after seven days; V3 – after 28 days of CP administration (Friedman ANOVA, p < 0.001 for all)

Duration of hospitalization among patients admitted due to COVID-19-associated dyspnea compared to those admitted for other reasons. The boxplot demonstrates a significantly longer duration of hospitalization for patients with dyspnea (Mann-Whitney U test, p = 0.047)

The structure of number of patients differing in the assessment of the level of serological response in the consecutive days of the visits including A) hematocrit, B) lymphocytes, C) neutrophiles, D) eosinocytes, E) MCH (Mean corpuscular hemoglobin), F) platelets, G) monocytes levels. V0- first visit prior CP administration, V1 – subsequent visit after 3 days, V2 – subsequent visit after 7 days, V3 – subsequent visit after 28 days of CP administration

The number (percentage) of plasma recipients differed in categories depending on the results of biochemical, serological parameters in the subsequent visit days (V0 - before CP administration, V1 - after 3 days, V2 – 7 days, V3 – after 28 days of CP administration)

	V0 Before	V1 After 3 days	V2 After 7 days	V3 After 28 days	Chi-squared test
Leukocytes count	N = 108	N = 102	N= 101	N = 101
Below standard	14 (13.0%)	4 (3.9%)	3 (3.0%)	1 (1.0%)	χ² = 38.2
Standard	81 (75.0%)	83 (81.4%)	82 (81.2%)	64 (63.4%)	df = 6
Above standard	13 (12.0%)	15 (14.7%)	16 (15.8%)	36 (35.6%)	p < 0.001
Hemoglobin	N = 108	N = 111	N = 101	N = 101
Below standard	39 (36.1%)	50 (49.0%)	36 (35.6%)	23 (22.8%)	χ² = 18.3
Standard	69 (63.9%)	52 (51.0%)	64 (63.4%)	78 (77.2%)	df = 6
Above standard	0 (0.0%)	0 (0.0%)	1 (1.0%)	0 (0.0%)	p = 0.006
Hematocrit	N = 108	N = 102	N = 101	N = 101
Below standard	27 (25.0%)	37 (36.3%)	25 (24.8%)	14 (13.9%)	χ² = 17.0
Standard	79 (73.1%)	65 (63.7%)	76 (75.2%)	85 (84.2%)	df = 6
Above standard	2 (1.9%)	0 (0.0%)	0 (0.0%)	2 (2.0%)	p = 0.009
MCV	N = 108	N = 102	N = 101	N = 101
Below standard	3 (2.8%)	2 (2.0%)	2 (2.0%)	1 (1.0%)	χ² = 1.61
Standard	98 (90.7%)	91 (89.2%)	93 (92.1%)	93 (92.1%)	df = 6
Above standard	7 (6.5%)	9 (8.8%)	6 (5.9%)	7 (6.9%)	p = 0.952
MCH	N = 108	N = 102	N = 101	N = 101
Below standard	3 (2.8%)	2 (2.0%)	2 (2.0%)	1 (1.0%)	χ² = 18.6
Standard	104 (96.3%)	100 (98.0%)	99 (98.0%)	93 (92.1%)	df = 6
Above standard	1 (0.9%)	0 (0.0%)	0 (0.0%)	7 (6.9%)	p = 0.005
Platelets	N = 108	N = 102	N = 101	N = 101
Below standard	16 (14.8%)	6 (5.9%)	1 (1.0%)	1 (1.0%)	χ² = 69.8
Standard	88 (81.5%)	88 (86.3%)	80 (79.2%)	62 (61.4%)	df = 6
Above standard	4 (3.7%)	8 (7.8%)	20 (19.8%)	38 (37.6%)	p < 0.001
Neutrophiles	N = 108	N = 101	N = 100	N = 101
Below standard	12 (11.1%)	7 (6.9%)	5 (5.0%)	2 (2.0%)	χ² = 13.8
Standard	49 (45.4%)	57 (56.4%)	64 (64.0%)	54 (53.5%)	df = 6
Above standard	47 (43.5%)	37 (36.6%)	31 (31.0%)	45 (44.6%)	p = 0.032
Limphocytes	N = 108	N = 101	N = 100	N = 101
Below standard	85 (78.7%)	71 (70.3%)	59 (59.0%)	31 (30.7%)	χ² = 57.4
Standard	20 (18.5%)	28 (27.7%)	39 (39.0%)	65 (64.4%)	df = 6
Above standard	3 (2.8%)	2 (2.0%)	2 (2.0%)	5 (5.0%)	p < 0.001
Monocytes	N = 108	N = 101	N = 100	N = 101
Below standard	11 (10.2%)	9 (8.9%)	4 (4.0%)	3 (3.0%)	χ² = 18.9
Standard	90 (83.3%)	84 (83.2%)	84 (84.0%)	76 (75.2%)	df = 6
Above standard	7 (6.5%)	8 (7.9%)	12 (12.0%)	22 (21.8%)	p = 0.004
Eosynocytes	N = 108	N = 101	N = 100	N = 101	χ² = 26.2
Below standard	42 (38.9%)	28 (27.7%)	22 (22.0%)	9 (8.9%)	df = 3
Standard	66 (61.1%)	73 (72.3%)	78 (78.0%)	92 (91.1%)	p < 0.001
Basocytes	N = 108	N = 101	N = 100	N = 101	χ² = 8.07
Below standard	4 (3.7%)	0 (0.0%)	1 (1.0%)	0 (0.0%)	df = 3
Standard	104 (96.3%)	101 (100.0%)	99 (99.0%)	101 (100.0%)	p = 0.045
CRP	N = 109	N = 101	N = 104	N = 100
Below standard	0 (0,0%)	0 (0,0%)	1 (1,0%)	0 (0,0%)	χ² = 71,4
Standard	4 (3,7%)	7 (6,3%)	17 (16,3%)	43 (43,0%)	df = 6
Above standard	105 (96,3&)	94 (84,7%)	86 (82,7%)	57 (57,0%)	p < 0,001
Prokalcytoniny	N = 104	N = 97	N = 100	N = 97	χ² = 39,2
Standard	49 (47,1%)	49 (50,5%)	67 (67,0%)	83 (85,6%)	df = 3
Above standard	55 (52,9%)	48 (49,5%)	33 (33,0%)	14 (14,4%)	p < 0,001
Ferrytyna	N = 102	N = 96	N = 97	N = 96
Below standard	0 (0,0%)	0 (0,0%)	1 (1,0%)	0 (0,0%)	χ² = 9,78
Standard	12 (11,8%)	5 (5,2%)	6 (6,2%)	14 (14,6%)	df = 6
Above standard	90 (88,2%)	91 (94,8%)	90 (92,8%)	82 (85,4%)	p = 0,134
D-dimer	N = 106	N = 101	N = 97	N = 95	χ² = 6,56
Standard	38 (35,8%)	23 (22,8%)	21 (21,6%)	27 (28,4%)	df = 3
Above standard	68 (54,2%)	78 (77,2%)	76 (78,4%)	68 (71,6%)	p = 0,087
LDH	N = 106	N = 98	N = 99	N = 97
Below standard	1 (0,9%)	0 (0,0%)	1 (1,0%)	1 (1,0%)	χ² = 23,2
Standard	16 (15,1%)	13 (13,3%)	23 (23,2%)	37 (38,2%)	df = 6
Above standard	89 (84,0%)	85 (86,7%)	75 (75,8%)	59 (60,8%)	p < 0,001
pH	N = 104	N = 84	N = 89	N = 86
Below standard	3 (2,9%)	1 (1,2%)	0 (0,0%)	1 (1,2%)	χ² = 7,24
Standard	32 (30,8%)	37 (44,0%)	29 (32,6%)	28 (32,5%)	df = 6
Above standard	69 (66,3%)	46 (54,8%)	60 (67,4%)	57 (66,3%)	p = 0,299
PO₂	N = 104	N = 84	N = 89	N = 85
Below standard	64 (61,5%)	56 (66,7%)	63 (70,8%)	55 (64,7%)	χ² = 7,25
Standard	34 (32,7%)	17 (20,2%)	19 (21,3%)	22 (25,9%)	df = 6
Above standard	6 (5,8%)	11 (13,1%)	7 (7,9%)	8 (9,4%)	p = 0,298
PCO₂	N = 104	N = 84	N = 89	N = 86
Below standard	38 (36,5%)	17 (20,2%)	20 (22,5%)	20 (23,2%)	χ² = 9,69
Standard	63 (60,6%)	66 (78,6%)	67 (75,3%)	63 (73,3%)	df = 6
Above standard	3 (2,9%)	1 (1,2%)	2 (2,2%)	3 (3,5%)	p = 0,138
HCO₃	N = 104	N = 84	N = 89	N = 86
Below standard	7 (6,7%)	1 (1,2%)	0 (0,0%)	1 (1,2%)	χ² = 18,8
Standard	91 (87,5%)	75 (89,3%)	79 (88,8%)	69 (80,2%)	df = 6
Above standard	6 (5,8%)	8 (9,5%)	10 (11,2%)	16 (18,6%)	p = 0,005
BE	N = 102	N = 84	N = 89	N = 86
Below standard	6 (5,9%)	1 (1,2%)	0 (0,0%)	0 (0,0%)	χ² = 17,8
Standard	70 (68,6%)	49 (58,3%)	52 (58,4%)	58 (67,4%)	df = 6
Above standard	26 (25,5%)	34 (40,5%)	37 (41,6%)	28 (32,6%)	p = 0,007
O₂	N = 104	N = 84	N = 88	N = 85
Below standard	76 (73,1%)	70 (83,3%)	73 (83,0%)	62 (72,9%)	χ² = 6,47
Standard	27 (26,0%)	14 (16,7%)	15 (17,0%)	22 (25,9%)	df = 6
Above standard	1 (1,0%)	0 (0,0%)	0 (0,0%)	1 (1,2%)	p = 0,372

Number (percentage) of plasma recipients differing by the categories depending on the SARS-CoV-2 antibodies levels during a subsequent visits (V0 - test before CP administration, V2 - after 7 days, V3 - after 28 days of CP administration)

	V0 Before	V2 After 7 days	V3 After 28 days	Chi-square test
IgA anty-SARS-CoV-2	N = 108	N = 97	N = 96
Negative	34 (30.9%)	5 (5.2%)	0 (0.0%)	χ² = 52.8
Inconsistent	3 (2.7%)	2 (2.0%)	1 (1.0%)	df = 4
Positive	73 (66.4%)	90 (92.8%)	95 (99.0%)	p < 0.001^a
IgA anty-SARS-CoV-2	N = 108	N = 97	N = 96	χ² = 73.3
Me [Q1; Q3]	2.3 [1; 8]	18.1 [5; 22]	19.4 [10–21]	df = 2
Min – Max	0 – 25	1 – 24	1 – 25	p < 0.001^b
IgM anty-SARS-CoV-2	N = 108	N = 98	N = 96	χ² = 32.5
Negative	52 (47.3%)	19 (19.4%)	14 (14.6%)	df = 2
Positive	58 (52.7%)	79 (80.6%)	82 (85.4%)	p < 0.001^a
IgM anty-SARS-CoV-2	N = 108	N = 97	N = 96	χ² = 83.3
Me [Q1; Q3]	1.1 [0; 7]	10.2 [2; 27]	10.3 [3; 26]	df = 2
Min – Max	0 – 30	0 – 30	0 – 30	p < 0.001^b
IgG anty-SARS-CoV-2	N = 108	N = 98	N = 96	χ² = 53.5
Negative	38 (34.2%)	6 (6.1%)	1 (1.0%)	df = 2
Positive	73 (65.8%)	92 (93.9%)	95 (99.0%)	p < 0.001^a
IgG anty-SARS-CoV-2	N = 108	N = 97	N = 96	χ² = 125.8
Me [Q1; Q3]	4.5 [0.3; 16]	22.7 [10; 31]	31.2 [24; 37]	df = 2
Min – Max	0 – 54.1	0 – 48.3	2.9 – 51.2	p < 0.001^b

The results of the ROC curves analysis of variables for the assessment of the likelihood of death caused by COVID-19 infection

Variable (parameter)	Cut-off value	Sensitivity	Specificity	AUC (95% CI)	p value
Duration from the first COVID-19 symptom to CP administration (days)	<9	0.510	0.500	0.598 (0.388–0.807)	p = 0.797
Plasma titers	<2000	0.625	0.400	0.536 (0.342–0.730)	p = 0.670
Age (years old)	≥68	0.750	0.840	0.842 (0.706–0.978)	p < 0.001
BMI (kg/m²)	≥30	0.500	0.760	0.577 (0.372–0.781)	p = 0.136

Analysis of hospitalization duration across various patient subgroups stratified by key clinical and demographic parameters, including time between symptom onset and CP administration, donor plasma titer levels, age, BMI, and presence of dyspnea at hospital admission

Patients subgroups	Me (Q1 – Q3)	Min – Max	p
Time between symptoms and CP administration <9 days	11 (9 – 14)	2 – 67	0.057
Time between symptoms and CP administration □9 days	10 (8 – 12)	3 – 31	0.057
Donor plasma titer = 2000	10 (8 – 14)	2 – 67	0.907
Donor plasma titer < 2000	10 (8 – 13)	3 – 52	0.907
Age < 68 years old	10 (8 – 13)	2 – 52	0.510
Age □ 68 years old	12 (8 – 16)	2 – 67	0.510
BMI □ 30 kg/m²	10 (8 – 14)	2 – 67	0.684
BMI > 30 kg/m²	10 (9 – 13)	2 – 27	0.684
Hospitalization time (days): Dyspnea during the admission to the hospital	10 (9 – 14)	2 – 67	0.047
Lack of dyspnea	9 (6 – 10)	4 – 18	0.047

Post-hoc pairwise comparisons of overall survival probability based on hematocrit, monocyte, and pCO2 levels after CP transfusion

Subgroups	Hematocrit	Monocytes	pCO₂
Normal vs Below standard	p = 0.257	p = 0.006	p = 0.653
Normal vs Above standard	p < 0.001	p = 0.283	p = 0.039
Below vs Above standard	p = 0.019	p = 0.512	p = 0.021

The assessment of parameters of convalescent plasma and their impact on COVID-19 symptoms

Figures & Tables

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Figure S1.

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The number (percentage) of plasma recipients differed in categories depending on the results of biochemical, serological parameters in the subsequent visit days (V0 - before CP administration, V1 - after 3 days, V2 – 7 days, V3 – after 28 days of CP administration)

Number (percentage) of plasma recipients differing by the categories depending on the SARS-CoV-2 antibodies levels during a subsequent visits (V0 - test before CP administration, V2 - after 7 days, V3 - after 28 days of CP administration)

The results of the ROC curves analysis of variables for the assessment of the likelihood of death caused by COVID-19 infection

Analysis of hospitalization duration across various patient subgroups stratified by key clinical and demographic parameters, including time between symptom onset and CP administration, donor plasma titer levels, age, BMI, and presence of dyspnea at hospital admission

Post-hoc pairwise comparisons of overall survival probability based on hematocrit, monocyte, and pCO2 levels after CP transfusion

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