A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Patients’ Inclusion Criteria and Longitudinal Analyses Performed
2.3. CP Infusion Treatment Protocol
2.4. CP Donors
2.5. Detection of Anti-SARS-CoV-2 Antibodies in the Donors and Recipients
2.6. Statistical Analysis
3. Results
3.1. CP Donors
3.2. CP Recipients: Clinical Characteristics
3.3. Control Group
3.4. Outcomes
3.5. Adverse Events
3.6. Longitudinal Analysis of Clinical and Laboratory Parameters in the CP Group
3.7. Subgroup Analysis by the Level of Antibodies at Baseline
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Convalescent Plasma Group (n = 59) | Control Group (n = 59) | p-Value | |
---|---|---|---|
Age, median (IQR) | 59 (18.0) | 59 (20) | 0.893 |
<60 years % | 45.8 | 50.8 | |
≥60 years % | 55.2 | 49.2 | |
Gender, % | 0.564 | ||
Female | 32.2 | 37.3 | |
Male | 67.8 | 62.7 | |
Comorbidities, % | 61.0 | 62.7 | 0.393 |
Diabetes | 19.3 | 28.3 | 0.269 |
Arterial hypertension | 29.8 | 37.7 | 0.382 |
Coronary artery disease | 7.0 | 13.2 | 0.282 |
Heart failure | 3.5 | 9.4 | 0.205 |
Pulmonary disease | 14.0 | 9.4 | 0.457 |
Renal impairment | 8.8 | 11.3 | 0.276 |
Solid tumor | 1.8 | 7.5 | 0.658 |
Hematological malignancy | 3.5 | 1.9 | 0.603 |
Symptoms, % | |||
Fever | 98.2 | 96.6 | 0.571 |
Myalgia | 8.8 | 10.3 | 0.775 |
Cough | 56.1 | 48.3 | 0.401 |
Dyspnea | 36.8 | 53.4 | 0.08 |
Loss of taste | 8.8 | 3.4 | 0.235 |
Anosmia | 5.3 | 5.2 | 0.983 |
Diarrhea | 19.3 | 19.0 | 0.964 |
Baseline laboratory parameters, median (IQR) | |||
Lymphocytes, (109/L, NR: 1.1–4.0) | 1.17 (0.7) | 1.02 (0.6) | 0.207 |
Platelets, (109/L, NR: 130–400) | 196 (101.5) | 197 (75.3) | 0.721 |
CRP, (mg/L, NR: 0.00–6.00) | 47 (50.3) | 44.8 (71.9) | 0.772 |
Fibrinogen, (mg/dL, NR: 200–400) | 485 (173) | 477 (253.9) | 0.631 |
LDH, (U/L, NR: 135–225) | 315 (167.8) | 277 (127.3) | 0.165 |
Ferritin, (ng/mL, NR: 13–150) | 597 (451.5) | 474 (167.9) | 0.443 |
Intereukin-6, (pg/mL, NR: <7) | 30.5 (43.6) | ||
SARS-CoV-2 PCR CT value | 26.8 (6.9) | 27.5 (9.3) | 0.700 |
Percentage of infiltrates at baseline CT, % | 0.117 | ||
<25 | 29.1 | 39.6 | |
25–50 | 38.2 | 43.8 | |
50–75 | 25.5 | 8.3 | |
≥75% | 7.3 | 8.3 | |
Concomitant dexamethasone, % | 59.3 | 49.2 | 0.270 |
Baseline SOFA score | 5 (4) | 4 (4) | 0.295 |
Time from first symptom to diagnosis, median (IQR) | 3 (4] | 4 (3) | 0.265 |
Time from first symptom to CP infusion, median (IQR) | 7 (4) | ||
Time from diagnosis to CP infusion, median (IQR) | 3 (3) |
Convalescent Plasma Group (n = 59) | Control Group (n = 59) | p-Value 1 | |
---|---|---|---|
Status at day 14 | n (%) | n (%) | 0.249 |
Discharged | 21 (35.6) | 31 (52.5) | |
Hospitalized | 30 (50.8) | 18 (30.5) | |
In ICU | 8 (13.6) | 5 (8.5) | |
Death | 0 (0.0) | 5 (8.5) | |
Status at day 28 | n (%) | n (%) | 0.566 |
Discharged | 48 (81.4) | 46 (78.0) | |
Hospitalized | 5 (8.5) | 5 (8.5) | |
In ICU | 5 (8.5) | 3 (5.1) | |
Death | 1 (1.7) | 5 (8.5) | |
Status at end of follow-up | n (%) | n (%) | 0.106 |
Discharged | 56 (94.9 | 51 (86.4) | |
Hospitalized | 0 (0.0) | 0 (0.0) | |
In ICU | 1 (1.7) | 0 (0.0) | |
Death | 2 (3.4) | 8 (13.6) | |
Follow-up, median (IQR) | 29 (24) | 10 (11) | <0.001 |
Duration of hospital stay, median (IQR) | 15 (10) | 10 (11) | 0.006 |
Admission to ICU, n (%) | 16 (27.1) | 9 (15.3) | 0.116 |
Exit from ICU, n (%) | 13 (22.0) | 2 (3.4) | 0.014 |
Time to exit from ICU, median (IQR) | 12.5 (37.25) | 7 (NC) | 0.824 |
Intubation, n (%) | 16 (27.1) | 8 (13.6) | 0.068 |
Extubation, n (%) | 13 (22.0) | 1 (1.7) | 0.006 |
Time to extubation, median (IQR) | 15 (35.5) | 17.5 (NC) | 0.837 |
Duration of oxygen support, median (IQR) | 7 (11.5) | NA | |
Achievement of negative PCR, n (%) | 37 (62.7) | 19 (52.8) | 0.167 |
Time to PCR negativity, median (IQR) | 14 (14) | 9.5 (14.8) | 0.007 |
Variables 2 | HR (95%CI) | p-Value 1 |
---|---|---|
Age | 1.08 (1.01–1.14) | 0.024 |
Male gender | 1.22 (0.34–4.35) | 0.761 |
Percentage of infiltrates at CT | 2.53 (1.24–5.19) | 0.011 |
Baseline SOFA score | 1.29 (0.98–1.72) | 0.073 |
Dexamethasone co-medication | 1.43 (0.39–5.19) | 0.586 |
Convalescent plasma infusion | 0.05 (0.01–0.43) | 0.006 |
N_RBD (In-house ELISA), below median | 0.07 (0.007–0.76) | 0.029 |
N_RBD (In-house ELISA), above median | 0.04 (0.002–0.62) | 0.021 |
Spike (In-house ELISA), below median | 0.07 (0.007–0.77) | 0.029 |
Spike (In-house ELISA), above median | 0.04 (0.002–0.61) | 0.012 |
Spike_RBD (In-house ELISA), below median | 0.07 (0.006–0.74) | 0.027 |
Spike_RBD (In-house ELISA), above median | 0.04 (0.002–0.58) | 0.019 |
ID50, below median | 0.08 (0.007–0.88) | 0.039 |
ID50, above median | 0.04 (0.003–0.55) | 0.016 |
Variables | HR (95%CI) | p-Value 1 |
---|---|---|
Age | 1.04 (0.97–1.12) | 0.233 |
Percentage of infiltrates at CT | 3.87 (1.56–9.58) | 0.003 |
Convalescent plasma infusion | 0.04 (0.004–0.36) | 0.005 |
Subgroup analyses by level of plasma antibodies (cut -off: median) 2 | ||
N_RBD (In-house ELISA), below median | 0.08 (0.006–1.09) | 0.059 |
N_RBD (In-house ELISA), above median | 0.02 (0.001–0.34) | 0.007 |
Spike (In-house ELISA), below median | 0.10 (0.008–1.21) | 0.070 |
Spike (In-house ELISA), above median | 0.02 (0.001–0.33) | 0.007 |
Spike_RBD (In-house ELISA), below median | 0.08 (0.007–1.003) | 0.051 |
Spike_RBD (In-house ELISA), above median | 0.02 (0.001–0.35) | 0.008 |
ID50, below median | 0.14 (0.01–1.91) | 0.139 |
ID50, above median | 0.02 (0.001–0.29) | 0.016 |
Variables | Effect Estimate (95%CI) | p-Value # |
---|---|---|
Clinical status at day 14 | OR: 1.50 (0.76–2.98) | 0.244 1 |
Clinical status at day 28 | OR: 0.77 (0.31–1.88) | 0.565 1 |
Clinical status at end of follow-up | OR: 0.33 (0.08–1.33) | 0.119 1 |
Hospital discharge | OR: 2.93 (0.74–11.64) | 0.127 2 |
Time to hospital discharge | HR: 0.68 (0.46–0.99) | 0.05 3 |
Intubation | OR: 2.37 (0.93–6.01) | 0.072 2 |
Time to intubation | HR: 0.48 (0.19–1.21) | 0.122 3 |
Extubation | OR: 30.3 (2.64–348.9) | 0.006 2 |
Time to extubation | HR: 0.68 (0.08–5.44) | 0.712 3 |
Exit from ICU | OR: 15.16 (2.02–113.3) | 0.008 2 |
Time to exit from ICU | HR: 0.54 (0.07–4.41) | 0.566 3 |
Achievement of PCR negativity | OR: 1.84 (0.78–4.36) | 0.168 2 |
Time to reach PCR negativity | HR: 0.74 (0.42–1.29) | 0.741 3 |
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Pappa, V.; Bouchla, A.; Terpos, E.; Thomopoulos, T.P.; Rosati, M.; Stellas, D.; Antoniadou, A.; Mentis, A.; Papageorgiou, S.G.; Politou, M.; et al. A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis. Microorganisms 2021, 9, 806. https://doi.org/10.3390/microorganisms9040806
Pappa V, Bouchla A, Terpos E, Thomopoulos TP, Rosati M, Stellas D, Antoniadou A, Mentis A, Papageorgiou SG, Politou M, et al. A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis. Microorganisms. 2021; 9(4):806. https://doi.org/10.3390/microorganisms9040806
Chicago/Turabian StylePappa, Vasiliki, Anthi Bouchla, Evangelos Terpos, Thomas P. Thomopoulos, Margherita Rosati, Dimitris Stellas, Anastasia Antoniadou, Andreas Mentis, Sotirios G. Papageorgiou, Marianna Politou, and et al. 2021. "A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis" Microorganisms 9, no. 4: 806. https://doi.org/10.3390/microorganisms9040806