Convalescent plasma transfusion shows ‘encouraging’ COVID-19 results at one institution
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Over 40% of patients with severe COVID-19 improved within a week of convalescent plasma infusion, with more than 50% alive and discharged by 28 days, according to a study presented at the virtual ASH Annual Meeting and Exposition.
Results of the study, conducted at Yale-New Haven Health System, should be confirmed in larger studies, according to the researchers.
“Administration of COVID-19 convalescent plasma (CCP), collected from individuals who have recovered from COVID-19 infection and thus are believed to have mounted an immune response, is a way to passively transfer anti-SARS-CoV-2 antibodies to those with active infection in attempt to neutralize the virus through a variety of proposed mechanisms,” Sabrina L. Browning, MD, hematologist at Yale Medicine, told Healio. “Although larger, randomized controlled trials are necessary to confirm the efficacy of this treatment, CCP has served as an easily accessible therapeutic option early in the COVID-19 pandemic.”
Browning and colleagues evaluated data of 105 patients aged 18 years or older (median age, 62 years; range, 28-88; 62.9% men) treated at one of five hospitals of the Yale-New Haven Health System for severe or life-threatening COVID-19. Most patients were of nonwhite race or ethnicity (56.2%), with 18.1% being Black and 33.3% identifying as Hispanic or Latinx.
Further, 47.6% of patients had a BMI greater than 30 kg/m2, and researchers classified 13.3% as extremely obese, with a BMI greater than 40 kg/m2. Diabetes (42.9%), hypertension (61.9%) and hyperlipidemia (53.3%) were “highly prevalent” among the patients, Browning said during her presentation.
Patients received one CCP unit via the national Expanded Access Program for convalescent plasma, led by Mayo Clinic, and underwent assessment at 7, 14 and 28 days following the transfusion.
“On review of available literature at that time, our team determined that transfusion of one unit of CCP was likely to be effective and safe and that it was appropriate to standardize this among our patient population,” Browning told Healio. “Additionally, given initial concern that transfusion of CCP may further potentiate the prothrombotic state thought to exist in some patients with COVID-19 at baseline, it was determined that all patients receiving CCP would be started on at least intermediate-dose anticoagulation at the time of transfusion, with continuation for at least 72 hours post-CCP.”
In addition to CCP, 79% of patients received hydroxychloroquine, 79% received tocilizumab (Actemra, Genentech) and 23.8% receive remdesivir (Veklury, Gilead).
Results showed 42.9% of patients demonstrated improvement by day 7 following transfusion, based on a decrease in their WHO Ordinal Scale score — with a median time to improvement of 4 days — whereas 9.5% of patients had a higher WHO score, indicating worsening oxygenation.
Overall, 52.4% of patients were alive and discharged by day 28.
Given that these patients all had severe COVID-19, this rate of improvement is encouraging, according to Browning.
“The available evidence from studies assessing the benefit of CCP in patients with COVID-19 has been mixed,” she told Healio. “While our results are certainly encouraging given the improvements observed in patients with severe COVID-19 and high expected mortality, further randomized controlled trials are necessary to confirm this benefit.”
The mortality rate increased from 10.48% at 7 days to 20.95% at 14 days and 28.57% at 28 days following the transfusion.
Almost all the patients (n = 91) required ICU care during their hospital stay, with 87 patients in the ICU at the time of the transfusion. Of this latter group, 56 (64.4%) de-escalated to non-ICU care a median 8 days following the transfusion, and 55 (63.2%) were eventually discharged from the hospital a median 14 days (range, 2-103) following the transfusion.
Median time from transfusion to death among nonsurvivors was 10 days (range, 1-76).
Researchers noted that nonsurvivors experienced a slightly longer mean time from admission to CCP transfusion (8.6 days vs. 6.9 days) and from positive SARS-CoV-2 polymerase chain reaction to transfusion (9.7 days vs. 7.3 days) than survivors.
Data showed greater risk for mortality with a D-dimer level greater than 5 mg/L fibrinogen-equivalent units at 24 hours (OR = 2.79; 95% CI, 1.18-6.72), 48 hours (OR = 3.64; 95% CI, 1.44-9.7) and 72 hours (OR = 2.99; 95% CI, 1.23-7.66) following transfusion. Twelve patients received an escalation of anticoagulation dosing from prophylactic/intermediate to therapeutic during the week following CCP transfusion.
“This observation raises the question of whether COVID-19 convalescent plasma therapy may potentiate the increased thrombotic risk and endotheliopathy now believed to be major contributors to disease physiology in COVID-19,” Browning said during her presentation.
Researchers also found that a ferritin level greater than 3,000 ng/mL on the day of the transfusion was associated with mortality (OR = 5.14; 95% CI, 1.34-19.68).
Researchers are planning additional research, including to assess hemostatic balance in donor plasma and to compare patients with COVID-19 who did and did not receive CCP.
“Our group is currently participating in a multi-institutional, randomized, placebo-controlled clinical trial investigating outcomes with CCP in patients with COVID-19,” Browning said. “We are also interested in exploring further whether patients who have recovered from COVID-19 and may be candidates to donate their plasma still have a procoagulant state. This would be important knowledge when considering how to safely administer CCP to patients.”
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Browning SL, et al. Abstract 101. Presented at: ASH Annual Meeting and Exposition (virtual meeting); Dec. 5-8, 2020.
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