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

Agnieszka Kuś

Agnieszka Kuś

Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical UniversityWroclaw, Poland
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Kuś, Agnieszka
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Szymon Wieczorek

Szymon Wieczorek

Faculty of Medicine, Wroclaw Medical UniversityWroclaw, Poland
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Wieczorek, Szymon
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Jarosław Dybko

Jarosław Dybko

Department of Hematology and Cellular Transplantation, Lower Silesian Oncology CenterWroclaw, Poland
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Dybko, Jarosław
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Małgorzata Szymczyk-Nużka

Małgorzata Szymczyk-Nużka

Regional Centre of Transfusion Medicine and Blood Bank (RCTMBB-W)Wroclaw, Poland
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Szymczyk-Nużka, Małgorzata
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Aleksandra Butrym

Aleksandra Butrym

Department of Cancer Prevention and Therapy, Wroclaw Medical UniversityWroclaw, Poland
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Butrym, Aleksandra
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Krzysztof Dudek

Krzysztof Dudek

Faculty of Mechanical Engineering, Wroclaw University of Science and TechnologyWroclaw, Poland
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Dudek, Krzysztof
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Grzegorz Mazur

Grzegorz Mazur

Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical UniversityWroclaw, Poland
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Mazur, Grzegorz
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Siddarth Agrawal

Siddarth Agrawal

Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical UniversityWroclaw, Poland
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Agrawal, Siddarth
  
17 abr 2025
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Categoría del artículo: Original Study
Publicado en línea: 17 abr 2025
Páginas: 35 - 49
Recibido: 29 jul 2024
Aceptado: 19 feb 2025
DOI: https://doi.org/10.2478/ahem-2025-0006
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© 2025 Agnieszka Kuś et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1.

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 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%)

Figure 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
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

Figure 3.

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
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

Figure 4.

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
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

Figure 5.

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)
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)

Figure S1.

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)
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)

Figure S2.

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 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 < 0.001a
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 < 0.001b
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 < 0.001a
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 < 0.001b
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 < 0.001a
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 < 0.001b

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
Donor plasma titer = 2000 10 (8 – 14) 2 – 67 0.907
Donor plasma titer < 2000 10 (8 – 13) 3 – 52
Age < 68 years old 10 (8 – 13) 2 – 52 0.510
Age □ 68 years old 12 (8 – 16) 2 – 67
BMI □ 30 kg/m2 10 (8 – 14) 2 – 67 0.684
BMI > 30 kg/m2 10 (9 – 13) 2 – 27
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

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
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