Elliott Bennett-Guerrero1, Jamie L Romeiser1, Lillian R Talbot2, Tahmeena Ahmed3, Linda J Mamone3, Sunitha M Singh4, Janet C Hearing5, Huda Salman6, Dishaw D Holiprosad7, Alex T Freedenberg7, Jason A Carter2, Nicholas J Browne7, Megan E Cosgrove7, Margaret E Shevik2, Laura M Generale7, Margaret A Andrew8, Sharon Nachman9, Bettina C Fries10. 1. Department of Anesthesiology, Stony Brook University, Stony Brook, NY. 2. MSTP, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY. 3. Department of Pathology/Blood Bank, Stony Brook Medicine, Stony Brook, NY. 4. Enhanced Recovery Coordinator, Stony Brook Medicine, Stony Brook, NY. 5. Department of Microbiology and Immunology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY. 6. Department of Medicine/Hematology, Stony Brook Medicine, Stony Brook, NY. 7. Renaissance School of Medicine at Stony Brook University, Stony Brook, NY. 8. Cancer Center Clinical Trials, Stony Brook Medicine, Stony Brook, NY. 9. Department of Pediatrics, Stony Brook Medicine, Stony Brook, NY. 10. Division of Infectious Diseases, Attending at U.S. Department of Veterans Affairs-Northport VA Medical Center, Northport, NY.
Abstract
OBJECTIVES: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. DESIGN: Double-blind randomized controlled trial. SETTING: Hospital in New York. PATIENTS: Patients with polymerase chain reaction documented coronavirus disease 2019 infection. INTERVENTIONS: Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. MEASUREMENTS AND MAIN RESULTS: Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. CONCLUSIONS: Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.
OBJECTIVES: Four peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome. DESIGN: Double-blind randomized controlled trial. SETTING: Hospital in New York. PATIENTS: Patients with polymerase chain reaction documented coronavirus disease 2019 infection. INTERVENTIONS: Patients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients. MEASUREMENTS AND MAIN RESULTS: Enrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small. CONCLUSIONS: Administration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.
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