Evaluation of a COVID-19 convalescent plasma program at a U.S. academic medical center

Abstract

Amidst the therapeutic void at the onset of the COVID-19 pandemic, a critical mass of scientific and clinical interest coalesced around COVID-19 convalescent plasma (CCP). To date, the CCP literature has focused largely on safety and efficacy outcomes, but little on implementation outcomes or experience. Expert opinion suggests that if CCP has a role in COVID-19 treatment, it is early in the disease course, and it must deliver a sufficiently high titer of neutralizing antibodies (nAb). Missing in the literature are comprehensive evaluations of how local CCP programs were implemented as part of pandemic preparedness and response, including considerations of the core components and personnel required to meet demand with adequately qualified CCP in a timely and sustained manner. To address this gap, we conducted an evaluation of a local CCP program at a large U.S. academic medical center, the University of North Carolina Medical Center (UNCMC), and patterned our evaluation around the dimensions of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to systematically describe key implementation-relevant metrics. We aligned our evaluation with program goals of reaching the target population with severe or critical COVID-19, integrating into the structure of the hospital-wide pandemic response, adapting to shifting landscapes, and sustaining the program over time during a compassionate use expanded access program (EAP) era and a randomized controlled trial (RCT) era. During the EAP era, the UNCMC CCP program was associated with faster CCP infusion after admission compared with contemporaneous affiliate hospitals without a local program: median 29.6 hours (interquartile range, IQR: 21.2-48.1) for the UNCMC CCP program versus 47.6 hours (IQR 32.6-71.6) for affiliate hospitals; (P<0.0001). Sixty-eight of 87 CCP recipients in the EAP (78.2%) received CCP containing the FDA recommended minimum nAb titer of ≥1:160. CCP delivery to hospitalized patients operated with equal efficiency regardless of receiving treatment via a RCT or a compassionate-use mechanism. It was found that in a highly resourced academic medical center, rapid implementation of a local CCP collection, treatment, and clinical trial program could be achieved through re-deployment of highly trained laboratory and clinical personnel. These data provide important pragmatic considerations critical for health systems considering the use of CCP as part of an integrated pandemic response.

Fig 1. CCP administration process schematic.

Steps, eligibility criteria, and personnel involved in administering COVID-19 Convalescent Plasma (CCP) in the inpatient setting at The University of North Carolina Medical Center (UNCMC). The major process events of admission, enrollment, and infusion depicted in Fig 1 are scaled proportionally to the median time intervals spent on these activities at UNCMC. EAP = expanded access program, PCR = polymerase chain reaction, RCT = randomized controlled trial, GI = gastrointestinal, ICU = intensive care unit, ID = infectious diseases, MD = medical doctor, APP = advanced practice provider, RN = registered nurse, NP = nurse practitioner, QC = quality control.

Fig 2. Time to CCP infusion comparisons.

(A) Time from admission to CCP infusion of recipients in the UNCMC EAP (blue circles) versus affiliates EAP (black squares) versus affiliates EUA (grey inverted triangles). (B) Time from admission to enrollment, enrollment to CCP infusion and admission to CCP infusion for recipients in the UNCMC EAP comparing those that received CCP units from the UNCMC Blood Donation Center (dark blue open circles) versus a national vendor (light blue open squares). (C) Time from admission to CCP infusion for type of EAP consent obtained at UNCMC (participant consent in light blue circles, LAR consent in dark blue circles, 2MD in open squares). (D) During the CCP EAP era at UNCMC, first comparison is time from admission to remdesivir for all who received remdesivir (dark blue open circles) versus time from admission to CCP infusion of EAP participants (middle blue circles); second comparison is time from admission to remdesivir for all who received remdesivir and CCP (light blue open squares) versus those who received only remdesivir (black open triangles). (E) During the CCP EAP era at UNCMC, time from admission to remdesivir: first comparison is between those that received remdesivir in the ICU (middle blue circles) versus non-ICU (dark blue squares); second comparison is between those that received remdesivir and CCP (middle blue open circles) versus only remdesivir in the non-ICU (dark blue open squares); third comparison is between those that received remdesivir and CCP (middle blue circles) versus only remdesivir in the ICU (dark blue squares). Medians are reported. P values obtained via a non-parametric Mann-Whitney U test.

Fig 3. Time to CCP infusion comparisons.

(A). Time from admission to enrollment, enrollment to CCP infusion and admission to CCP infusion via the EAP at UNCMC in the ICU (blue open circles) versus the non-ICU (black open squares). (B) Time from admission to CCP infusion via the EAP at UNCMC for those admitted during the day shift (7am-7pm) (middle blue open squares) versus the night shift (7pm-7am) (dark blue squares). Medians are reported. P values obtained via a non-parametric Mann-Whitney U test.

Fig 4. Proportions and cumulative titered units collected and transfused during the EAP era at UNCMC.

(A) Monthly proportions of low (gray) versus standard (blue) versus high (black) titered units collected. Percentages at tops of bars are cumulative proportions of standard + high titered units. (B) Monthly proportions of low (gray) versus standard (blue) versus high (black) titered units transfused. Percentages at tops of bars are cumulative proportions of standard + high titered units. (C) Cumulative total units collected and transfused over time, cumulative units with titers ≥1:160 collected and transfused over time, cumulative national supplier units transfused over time.

Fig 5. Time from admission to CCP infusion of EAP and RCT recipients at UNCMC and of EUA recipients at affiliates.

UNCMC EAP reported in middle blue circles, UNCMC RCT reported in dark blue squares, Affiliates EUA reported in gray open squares. Medians are reported. P values obtained via a non-parametric Mann-Whitney U test.