Retention of hemostatic and immunological properties of frozen plasma and COVID‐19 convalescent apheresis fresh‐frozen plasma produced and freeze‐dried in Canada

Abstract

Background: Randomized clinical trial data show that early plasma transfusion may save lives among trauma patients. Supplying plasma in remote environments is logistically challenging. Freeze-dried plasma (FDP) offers a possible solution.Study Design and Methods: A Terumo BCT plasma freeze-drying system was evaluated. We compared pooled frozen plasma (FP) units with derived Terumo BCT FDP (TFDP) units and pooled COVID-19 convalescent apheresis fresh-frozen plasma (CC-AFFP) with derived CC-TFDP units. Parameters measured were: coagulation factors (F) II; V; VII; VIII; IX; XI; XIII; fibrinogen; Proteins C (PC) and S (PS); antithrombin (AT); α 2 -antiplasmin (α 2 AP); ADAMTS13; von Willebrand Factor (vWF); thrombin-antithrombin (TAT); D-dimer; activated complement factors 3 (C3a) and 5 (C5a); pH; osmolality; prothrombin time (PT); and activated partial thromboplastin time (aPTT).Antibodies to SARS-CoV-2 in CC-AFFP and CC-TFDP units were compared by plaque reduction assays and viral protein immunoassays. Results: Most parameters were unchanged in TFDP versus FP or differed ≤15%. Mean aPTT, PT, C3a, and pH were elevated 5.9%, 6.9%, 64%, and 0.28 units, respectively, versus FP. CC-TFDP showed no loss of SARS-CoV-2 neutralization titer versus CC-AFFP and no mean signal loss in most pools by viral protein immunoassays.

Rejuvenated and safe: Freeze‐dried plasma for the 21st century

“…These investigators used convalescent plasma donations with titers below the cut-off for use in the CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) RCT 27 to produce FDP by the Terumo BCT method, and demonstrated no loss of SARS-CoV-2 neutralization activity for all COVID-19 convalescent FDP units pools tested relative to the plasma pools from which they were derived. 3 Thus, CONCOR-1 yielded an additional finding beyond the rigorous demonstration that convalescent plasma transfusion did not reduce the 30-day risk of intubation or death from COVID-19. 27 While both current FDP studies employed plasma testing negative for all mandated infectious disease markers as starting material, there is no technical reason why pathogen-reduced plasma could not be freeze-dried in either system.…”

“…Sheffield et al took advantage of the availability of COVID‐19 convalescent plasma to test the reasonable but previously untested assumption that IgG activity in plasma would be conserved after freeze‐drying. These investigators used convalescent plasma donations with titers below the cut‐off for use in the CONvalescent Plasma for Hospitalized Adults With COVID‐19 Respiratory Illness (CONCOR‐1) RCT 27 to produce FDP by the Terumo BCT method, and demonstrated no loss of SARS‐CoV‐2 neutralization activity for all COVID‐19 convalescent FDP units pools tested relative to the plasma pools from which they were derived 3 . Thus, CONCOR‐1 yielded an additional finding beyond the rigorous demonstration that convalescent plasma transfusion did not reduce the 30‐day risk of intubation or death from COVID‐19 27 …”

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

“…Low-to-middle income countries (LMIC) are likely to benefit the most from CCP, given they cannot afford massive deployment of mAb or small-chemical antivirals. Research is ongoing to spare some of cold chain requirements for CCP relying over freeze-dried plasma (FDP), which has been shown to preserve nAb functions for months at ambient temperature (114).…”

A Qualitative Comparison of the Abbott SARS-CoV-2 IgG II Quant Assay against Commonly Used Canadian SARS-CoV-2 Enzyme Immunoassays in Blood Donor Retention Specimens, April 2020 to March 2021

“…This study compared the characteristics of the Abbott SARS-CoV-2 IgG II Quant assay (Abbott anti-spike [S]; Abbott, Chicago IL) against four other SARS-CoV-2 IgG assays that are commonly used in Canada ( 2 , 3 , 6 , 11 – 16 ). This study did not attempt to infer neutralizing antibody seroprotection from the seroprevalence estimates and did not assess seroprevalence in Canadian blood donors.…”

“…During this process, we used a variety of assays that have been widely used by our and other groups to assess SARS-CoV-2 seroprevalence in Canada. These included the Abbott Architect antinucleocapsid antigen IgG assay (Abbott-NP, Abbott, Chicago, IL), as well as three in-house Sinai Health (Toronto, ON, Canada) IgG enzyme-linked immunosorbent assays (ELISAs) utilizing recombinant viral antigens, full-length spike glycoprotein (S), spike glycoprotein receptor binding domain (RBD), and nucleocapsid (NP) ( 2 , 3 , 6 , 11 – 16 ). The Sinai Health IgG ELISAs were developed to allow for the scalable parallel detection of IgGs against the S, RBD, and NP.…”