ABSTRACT
Background The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. Though stopped early due to the lack of treatment benefit, the cost-effectiveness of convalescent plasma provides insight into its potential as an alternative treatment option in resource constrained settings.Methods Individual patient data on health outcomes and healthcare resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer’s perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L was measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of patients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled in the study were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses the costs from this population.Results 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 both arms (p = 0.85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms respectively (p = 0.46). The incremental cost was $4,458 and incremental quality-adjusted life day was − 0.078.Conclusion These results indicate that convalescent plasma was less effective and more costly than standard care in treating hospitalized patients with COVID-19. The sensitivity analysis yielded similar results to the base case analysis.
Subject(s)
COVID-19ABSTRACT
The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.
Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , DeathABSTRACT
Introduction: One of the possible mechanisms by which the new coronavirus (SARS-Cov2) could induce brain damage is the impairment of cerebrovascular hemodynamics (CVH) and intracranial compliance (ICC) due to the elevation of intracranial pressure (ICP). The main objective of this study was to assess the presence of CVH and ICC alterations in patients with COVID-19 and evaluate their association with short-term clinical outcome.Methods: 50 consecutive critically ill COVID-19 patients were studied with transcranial Doppler (TCD) and a non-invasive monitoring of ICC. Subjects were included upon ICU admission; CVH was evaluated using mean flow velocities in the middle cerebral arteries (mCBFV), pulsatility index (PI) and estimated cerebral perfusion pressure (eCPP) while ICC was assessed by using the P2/P1 ratio of estimated ICP curve (B4C device). The primary composite outcome was unsuccessful weaning from respiratory support or death on day 7.Results: At the first assessment (n= 50) only P2/P1 (1.20 [1.00-1.28] vs. 1.00 [0.88-1.16]; p=0.03) and eICP (14 [11-25] vs. 11 [7-15] mmHg; p=0.01) were significantly higher among patients with unfavorable outcome (UO) than others. Patients with UO had a significantly higher CVH/ICC score (9 [8-12] vs. 6 [5-7]; p<0.001) than those with favorable outcome; the area under the receiver operating curve (AUROC) for CVH/ICC score to predict UO was 0.86 (95% CIs 0.75-0.97); a score > 8.5 had 63 (46-77)% sensitivity and 87 (62-97)% specificity to predict UO. For those patients undergoing a second assessment (n=29) after a median of 11 (5-31) days, all measured variables were similar between the two time-points. No differences in the measured variables between ICU non-survivors (n=30) and survivors were observed.Conclusions: ICCI and CVH disturbances are often present in COVID-19 severe illness and could accurately predict early poor outcome.
Subject(s)
COVID-19 , Cerebrovascular DisordersABSTRACT
Background: Data on postoperative outcomes of the COVID-19 patient population is limited. We described COVID-19 patients who undergone a surgery and the pandemic impact on surgical activities. Methods: We conducted a multicenter cohort study between March 13 and June 19 2020. We included COVID-19 patients who underwent surgery in nine centres of the Province of Québec, the Canadian province most afflicted by the pandemic. We also included suspected COVID-19 (subsequently confirmed not to have COVID-19) patients and patients who had recovered from it. We collected data on baseline characteristics, postoperative complications and overall surgical activities performed in participating centres. Our primary outcome was 30-day mortality. Results: We included 44 COVID-19 patients, 18 suspected patients, and 18 patients who had recovered from COVID-19 at time of surgery. Among the 44 COVID-19 patients, 31 surgeries (71%) were urgent and 16 (36%) were major. In these patients, pulmonary complications were frequent (25%) and 30-day mortality was 15.9%. This mortality was higher in patients with symptoms (23.1%) compared to those without symptoms (5.6%), although not statistically significant (p = 0.118). Of the total 22 616 cases performed among participating centres during the study period, only 0.19% had COVID-19 at the time of surgery. Fewer procedures were performed during the study period compared to the same period in 2019 (44 486 cases). Conclusion: In this study, postoperative 30-day mortality in COVID-19 patients undergoing surgery was 15.9%. Although few surgeries were performed on COVID-19 patients, the pandemic impact on surgical activity volume was important. Trial registration ClinicalTrials.gov Identifier: NCT04458337