ABSTRACT
BACKGROUND: The use of convalescent plasma (CP) has been considered for its immunological mechanisms that could benefit patients in moderate and severe stages of COVID-19. This study evaluated the safety and efficacy of the use of donor CP for COVID-19. MATERIAL AND METHODS: A double-blind, randomized controlled clinical trial was conducted from May to October 2020. Thirty-nine participants with moderate (II) and severe (III) stages of COVID-19 confirmed by RT-PCR were included. The study randomization rate was set at 3:1. CPs were chosen for application with a neutralizing antibody titer of ≥1:32. RESULTS: We observed a significantly lower 21-day post-transfusion mortality HR: 0.17 (95.0% CI [0.07-0.45, p < 0.001]) in the group receiving CP compared with the control group; protective units (PU) in the group receiving convalescent plasma after seven days were significantly higher (512 (32-16,384) vs. 96 (32-256), p = 0.01); the PAO2/FIO2 index showed a significant improvement in the group receiving CP (251.01 (109.4) vs. 109.2 (62.4), p < 0.001, in the control group). CONCLUSION: CP is safe and effective, as it decreased mortality in the CP group compared with the control group.
ABSTRACT
A proof-of-concept study using thrombolysis with catheter-directed tissue plasminogen activator (tPA) and pulmonary angiography imaging was performed to visualize perfusion deficits and reperfusion/therapeutic effects of tPA. DESIGN: A prospective, open-label, compassionate study. Descriptive statistics were presented for categorical variables and as means with sds for continuous variables. The Wilcoxon test was used to determine the differences between the two-related samples and a t test for continuous variables. Statistical significance was set at p value of less than 0.05. Agreement between observations was evaluated using the Kappa Cohen index and overall agreement using the Fleiss Kappa coefficient. SETTING: A single COVID-19 ICU of Mexico´s General Hospital Dr Eduardo Liceaga. SUBJECTS: Fifteen patients with severe Delta variant severe acute respiratory syndrome coronavirus 2 infection, 18-75 years old, requiring mechanical ventilation with a persistent Fio2 requirement of 70% or higher and Pao2/Fio2 ratio (or imputed ratio) less than 150 for more than 4 hours. The coagulation inclusion criteria were International Society on Thrombosis and Haemostasis score greater than 5, and presence of a d-dimer greater than 1,200, with viscoelastic testing using rotational thromboelastometry (Instrumentation Laboratories, Mexico City, Mexico) showing both hypercoagulability (EXTEM amplitude at 5 min > 65 FIBTEM > 30) and hypofibrinolysis (EXTEM maximum lysis < 8%). INTERVENTIONS: Catheter-directed tPA angiography and iFlow system analysis to assess pre-tPA baseline pulmonary perfusion and changes in response to thrombolysis. RESULTS: Nine patients had microvascular filling defects demonstrated by angiography, and good agreement was found with iFlow analysis (Æ = 0.714). Statistically significant differences were identified in the area under the curve (AUC) region of interest/AUC reference tissue with and without filling defects in phase 2 DM -0.09206 (sd ± 0.16684) (p = 0.003). The Pao2/Fio2 values measured immediately and 48 hours after the procedure were significantly higher (p = 0.001 and p = 0.005, respectively). Statistically significant differences were found in d-dimer values (p = 0.007), Fio2 (p = 0.002), and oxygen saturation in arterial blood/Fio2 (p = 0.045), as well as in the number of patients who required prone positioning before, immediately after the procedure, and at 48 hours after the procedure (p = 0.002). CONCLUSIONS: Thrombolysis with catheter-directed tPA resulted in imaging evidence via pulmonary angiography and iFlow technology of improved lung perfusion in COVID-19 patients with severe respiratory failure.