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

Background

COVID-19 convalescent plasma (CCP) remains a potential therapy of COVID-19. The new CCP trial COVIC-19 takes into account lessons learned from previous trials, including the trial CAPSID, and combines them into a novel approach:

- CCP with very high concentrations of SARS-CoV-2 antibodies (≥4,000 BAU/ml) from donors with previous SARS-CoV-2 infection and vaccination - treatment of vulnerable persons early after symptom onset - Sequencing and cross-neutralization analyses to study viral evolution

Methods

We report the initial experience of collection of very high-titer plasma units for this COVIC-19 trial. We recruited 686 potential donors with previous SARS-CoV-2 infection (inf) and vaccination (vax) who passed initial eligibility check. Anti-SARS-CoV-2 antibody concentrations were measured by anti-SARS-CoV-2 QuantiVac ELISA (Euroimmun) and neutralization capacity was assessed in the GenScript Surrogat neutralization assay and in a pseudovirus neutralization assay. High S-Ab in the QuantiVac assay correlated with high neutralizing capacity.

Results

The average antibody concentration of those willing to donate was 4,298.58 BAU/ml. S-Ab was ≥4,000 BAU/ml in 41,1% of the individuals and did not significantly differ by gender or ABO type, but were higher among those who had received 3 vax (median 3,746 BAU/ml) or 4 vax (median 4,166 BAU/ml). Highest S-Ab were observed in those with a breakthrough infection after 2 vax, followed by a booster (median 5,159 BAU/ml, 64% ≥4,000 BAU/ml) or breakthrough inf after 3rd or 4th vax (median 3,846; 48% ≥4,000 BAU/ml). 158 qualified individuals ultimately donated CCP with anti-SARS-CoV-2 IgG concentrations ranging from 4,105 BAU/ml to 22,923 BAU/ml with a mean concentration of 8,019 BAU/ml.

Conclusion

Taking into account all eligibility criteria 31.9 % of the individuals screened could provide plasma units meeting the criteria for high-titer plasma for COVIC-19, however, only 23% actually donated. 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 start of apheresis to take advantage of the short period of very high mAb.

COVIC-19 is supported by BMBF.

Offenlegung Interessenkonflikt:

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