A Randomised Open-Label Trial of Early, Very High-Titre Convalescent Plasma Therapy in Clinically Vulnerable Individuals with Mild COVID-19 as model of early treatment in a pandemia with a new pathogen: Experience from collection of very high-titer plasma from superimmunized individuals

ABSTRACT

Background: COVID-19 convalescent plasma (CCP) remains a potential therapy of COVID-19, e.g. for new variants and for patients with impaired immune response. The trial COVIC-19 takes into account lessons learned from previous trials and combines it to a novel approach: * CCP with very high levels of SARS-CoV-2 antibodies from donors with previous SARS-CoV-2 infection (inf) and vaccination (vax) * Treatment early after symptom onset * Treatment of vulnerable persons (e.g. immunocompromised) * Study of immune escape Methods: We report the initial experience of collection of very high-titer plasma units (defined as >=4.000 BAU/ml in the QuantiVac ELISA) for this COVIC-19 trial. We recruited 348 potential donors (151 male, 197 female) who had passed initial eligibility check. S-Ab were measured by anti-SARS-CoV-2 QuantiVac ELISA (Euroimmun) mean 4229 BAU/ml (IQR 2.239-5.486 BAU/ml). High S-Ab in the QuantiVac assay correlated with high neutralizing capacity in the GenScript surrogat neutralization assay. S-Ab was >=4.000 BAU/ml in 25.1% of the individuals and did not significantly differ by gender or ABO type, but were higher among those who had received 3 vax (median 4.231 BAU/ml) or 2 vax (median 2.954 BAU/ml) or 1 vax (median 1.832 BAU/ml)(p<0.01). Result(s) We analyzed the association between the order of immunizing events and S-Ab. Highest S-Ab were observed among those with a breakthrough infection after 2 vax, followed by a booster (3rd dose post inf.) (median 5.840 BAU/ml;76.7% >=4.000 BAU/ml) or breakthrough inf after 3 vax (no further booster;median 3.841 BAU/ml;47.9% >=4.000 BAU/ml). S-Ab were lower in those with inf before vax followed by 1 vax (median 1.806 BAU/ml;18.1% >=4.000 BAU/ml) or >1 vax (median 2.586 BAU/ ml). S-Ab declined rapidly 42% of donors with S-Ab >=4.000 BAU/ml had declined below this threshold in the short interval until 1st plasmapheresis and further 6% until 2nd apheresis. Further follow-up will be presented. Conclusion(s) Taking into account all eligibility criteria only 8.6% of individuals willing to donate could provide plasma units meeting the criteria of high-titer plasma for COVIC-19. Collection of very-high titer plasma from super-immunized individuals with previous infection and vaccination is feasible, but requires substantial donor selection and rapid screening and immediate start of apheresis to take advantage of the short period of very high mAb.