COVID-19 Convalescent Plasma Decreased Oxygen Requirement and Hospital Stay in COVID-19 Hospitalized Patients Including Those with Hematological Malignancies: A Report of 16 Patients
Authors: Ibrahim Moayed , Pal Priya , Niu Alex , Zwezdaryk Kevin , Tatje Elise , Ko Leta , Satyavarap Ishwaria , Jones Wallace , Nachabe Adeem , Luk Alfred , Mushatt David M , Halvorson Karin , Denson Joshua , Simeone Francesco , Smith Charles , Davis Gaynelle , Gill Sukhmani , McDougal April , Vigh Aniko , Peterson Tim , Ning Bo , Hu Tony , Socola Francisco , Safah Hana , Saba Nakhle S. 
Published: November 2020

Introduction
In the absence of effective and readily available therapy for COVID-19, immediate interventions to improve its mortality are a public health emergency. COVID-19 convalescent plasma (CCP) carries antibodies against SARS-CoV-2 and represents a promising approach. Studies regarding the clinical use of CCP have been inconsistent, and the optimal timing and frequency of CCP infusion remain largely unknown. Similarly, the role of CCP in cancer patients, particularly those with hematological malignancies (HM), remains unknown. Herein we describe the outcomes of 16 critically ill patients with COVID-19, including HM, who were treated with CCP with marked clinical improvement.
Methods
CCP donors donated 2-4 units each (200 ml per unit), 18 to 56 days following full recovery from COVID-19. 16 patients received CCP following informed consent. 5 patients were treated after obtaining individual emergency Investigational New Drug (eIND) from the FDA, while the remaining 11 patients were enrolled in our investigator-initiated clinical trial, Expanded Access to Convalescent Plasma to Treat and Prevent Pulmonary Complications Associated With COVID-19 (clinicaltrials.gov Identifier: NCT04358211). We used ELISA to determine the Spike protein IgG titers on most CCP units. Treatment was with a single unit of 200ml of CCP given over 1h, with the exception of patients 4 and 9 who received two units eight days apart.
Results
10 males and 6 females between the ages of 24-81 were treated, 6 of which with HM. 12 patients were diagnosed by an RT-PCR-based technique while 4 were diagnosed by the highly sensitive clustered regularly interspaced short palindromic repeats (CRISPR)-based qualitative COVID-19 assay. Interestingly, these 4 patients have HM and had multiple false negative RT-PCR results prior to the CRISPR diagnosis. The Spike protein IgG titers on CCP units used to treat patient-5, patient-6, patient-8, patient-9, patient-11, patient-13, patient-14, patient-15, and patient-16 were 1:1600, 1:3200, 1:3200, 1:800, 1:400, 1:1600, 1:3200, 1:6400, and 1:3200, respectively. At the time of CCP infusion, patients were either mechanically ventilated (5), on noninvasive support with high flow nasal cannula (4), bilevel ventilation (1), or nasal cannula (5). Only 1 patient was on room air at the time of CCP infusion. No adverse events were reported in all patients with the exception of a fever during CCP transfusion in patient-10 resulting in infusion of only 100 ml. Steady improvement in oxygenation levels was observed following each CCP infusion. All of the 5 intubated patients were extubated between 1- and 19-days post CCP infusion. The remaining 11 showed a dramatic decline in oxygen needs and did not require ventilatory support. Of the 16 patients included here, only 1 patient expired following extubation secondary to progression of medical co-morbidities and the family's decision to transition to comfort care. Among the 15 patients surviving, patient-12 remains inpatient for respiratory failure following extubation to tracheostomy, while the rest were successfully discharged including the 6 patients with HM (Figure 1). Although all of our patients showed improvement following CCP, we noted a strong correlation between early CCP infusion and clinical improvement (r=0.6, p=0.02, for correlation between time from disease onset to CCP, and time from CCP to oxygen independence or discharge).
Interpretation of the data could potentially be affected by the concomitant clinical trial enrollment of some patients. Patients 14, and 15 were enrolled in ACTT-1, a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of remdesivir in hospitalized adults diagnosed with COVID-19 (ClinicalTrials.gov Identifier: NCT04280705); patients 3, 15, and 16, were enrolled in REGN88, a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of sarilumab in hospitalized adults diagnosed with COVID-19 (ClinicalTrials.gov Identifier: NCT04327388), while patients 1, 2, 5 and 6 received remdesivir outside of a clinical trial context, and patients 5, 6, 7, 8 ,12, and 15 received dexamethasone.
Conclusion
While a randomized controlled clinical trial remains the gold standard, our limited data represent a signal that CCP is safe and efficacious in COVID-19 and underscores a potential role for passive immunity in this disease.

Disclosures
Safah: Astellas: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Honoraria; Verastem: Honoraria. Saba:Kyowa Kirin: Other: Advisory Board; Janssen: Other: Advisory Board, Speakers Bureau; AbbVie: Consultancy, Other: Advisory Board, Speakers Bureau; Pharmacyclics: Other: Advisory Board, Speakers Bureau; Kite: Other: Advisory Board.

OffLabel Disclosure:
COVID-19 convalescent plasma is under investigation as a source of passive immunity to patients with severe COVID-19 pulmonary disease. This report highlights some of the promising results so far, especially in patients with hematological malignancies.