Matched Cohort Study of Convalescent COVID-19 Plasma Treatment in Severely or Life Threateningly Ill COVID-19 Patients

Abstract

Background The utility of convalescent COVID-19 plasma (CCP) in the current pandemic is not well defined. We sought to evaluate safety and efficacy of CCP in severely or life threateningly ill COVID-19 patients when matched with a contemporaneous cohort. Methods Patients with severe or life threatening COVID-19 were treated with CCP according to FDA criteria, prioritization by an interdisciplinary team and based on CCP availability. Individual-level matched controls (1:1) were identified from patients admitted during the prior month when no CCP was available. Safety outcome was freedom from adverse transfusion reaction and efficacy outcome a composite of death or worsening O2 support. Demographic, clinical and laboratory data were analyzed by univariate and multivariable regression analyses accounting for matched design. Results Study patients (N=94, 47 matched pairs) were 62% male with mean age of 58 and 98% (90/94) were minority (53% Hispanic, 45% Black, non-Hispanic) in our inner-city population. Seven-day composite and mortality outcomes suggested a non-significant benefit in CCP treated patients (adjusted hazard ratio (aHR), 0.70; 95% confidence interval (CI), 0.23 to 2.12; P=0.52; aHR, 0.23; 95% CI, 0.04 to 1.51; P=0.13, respectively). Stratification by pre-transfusion mechanical ventilation status showed no differences between groups. No serious transfusion reactions occurred. Conclusion In this short-term matched cohort study, transfusion with CCP was safe and showed a non-significant association with study outcomes. Randomized and larger trials to identify appropriate timing and dosing of CCP in COVID-19 is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT04420988

A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis

“…These observations extend the beneficial effect of CP to intubated patients. Our findings are in accordance with other studies showing shorter duration in the ICU [29,39], reduction of the recovery time and duration of the infection for patients in the ICU [32] and reduction of mortality for intubated patients [38,44]; in contrast other trials, did not reveal a beneficial effect of CP for intubated patients [40,41,47].…”

“…In our study, we examined the beneficial effect of CP in patients with severe COVID-19 using a matched propensity score analysis. This strategy has already been used in other trials, resulting in contradictory results [21,23,30,[37][38][39][40][41][44][45][46][47]56]. In our study, the univariate analysis comparing the CP to the control group showed a significantly reduced risk of death.…”

“…Some other studies using comparison to a control group have also shown beneficial results in favor of CP for specific subpopulations, including a survival advantage for non-intubated patients [30], a reduction of disease severity for patients with ARDS [39], and a reduction of mortality for elderly-particularly female-patients admitted to ICU and with comorbidities [38]. On the contrary, other studies did not confirm these beneficial findings when comparing the intervention to a control group [45][46][47]. However, in one study, 86% of the patients were intubated and 70% had already high titers of anti-SARS-CoV-2 antibodies before infusion [45].…”

“…The data regarding the efficacy of CP in COVID-19 are gradually increasing, including small case series [25,34,36], observational studies [27,32,33,42,55], matched controlled studies [21,23,30,[37][38][39][40][41][44][45][46][47]56] and a few randomized controlled trials [22,24,26,28,29,35,43], with no definite conclusions. In the observational study by Salazar et al of 25 patients with severe and life threatening disease, the infusion of CP resulted in the improvement of disease severity in 76% of patients [33].…”

“…However, in one study, 86% of the patients were intubated and 70% had already high titers of anti-SARS-CoV-2 antibodies before infusion [45]. In other trials, anti-SARS-CoV-2 antibodies were not determined in the CP, which may have interacted with the negative results [46,47]. In one study, the CP was administered within 21 days after symptom onset [46].…”