Are convalescent plasma stocks collected during former COVID-19 waves still effective against current SARS-CoV-2 variants?

COVID-19 convalescent plasma (CCP) was among the few frontline therapies used to treat COVID-19. After large randomized controlled trials (RCTs) relying on late use in hospitalized patients and/or low antibody titres failed to meet their predefined primary endpoint, the infectious disease community reduced usage of CCP in favour of monoclonal antibodies. Consequently, there are CCP stocks at most transfusion centres worldwide, although scattered usage continues. Further, better designed RCTs are also being launched. The urgent question here is: should we use CCP units collected months before given the largely changed viral variant landscape? We review here in vitro evidence that discourages usage of such CCP units against Delta and other variants of concern. CCP collections should be continued in order to update the armamentarium of therapeutics against vaccine breakthrough infections or in unvaccinated patients and is especially relevant in next-generation RCTs.

Focosi D ，Franchini M ，Joyner MJ ，Casadevall A ... -  《-》

Variant of Concern-Matched COVID-19 Convalescent Plasma Usage in Seronegative Hospitalized Patients.

Franchini M ，Focosi D ，Percivalle E ，Beccaria M ，Garuti M ，Arar O ，Pecoriello A ，Spreafico F ，Greco G ，Bertacco S ，Ghirardini M ，Santini T ，Schiavulli M ，Stefania M ，Gagliardo T ，Sammartino JC ，Ferrari A ，Zani M ，Ballotari A ，Glingani C ，Baldanti F ... -  《Viruses-Basel》

Vaccination of COVID-19 convalescent plasma donors increases binding and neutralizing antibodies against SARS-CoV-2 variants.

COVID-19 convalescent plasma (CCP) was widely used as passive immunotherapy during the first waves of SARS-CoV-2 infection in the US. However, based on observational studies and randomized controlled trials, the beneficial effects of CCP were limited, and its use was virtually discontinued early in 2021, in concurrence with increased vaccination rates and availability of monoclonal antibody (mAb) therapeutics. Yet, as new variants of the SARS-CoV-2 spread, interest in CCP derived from vaccine-boosted CCP donors is resurging. The effect of vaccination of previously infected CCP donors on antibodies against rapidly spreading variants is still under investigation. In this study, paired-samples from 11 CCP donors collected before and after vaccination was tested to measure binding antibody levels and neutralization activity against the ancestral Wuhan-Hu-1 and SARS-CoV-2 variants (Wuhan-Hu-1 with D614G, alpha, beta, gamma, delta, epsilon) on the Ortho Vitros Spike Total Ig and IgG assays, the MSD V-PLEX SARS-CoV-2 arrays for IgG binding and ACE2 inhibition, and variant-specific Spike Reporter Viral Particle Neutralization (RVPN) assays. Binding and neutralizing antibodies were significantly boosted by vaccination, with several logs higher neutralization for all the variants tested post-vaccination compared to the pre-vaccination samples, with no difference found among the individual variants. Vaccination of previously infected individuals boosts antibodies including neutralizing activity against all SARS-CoV-2 variants.

Di Germanio C ，Simmons G ，Thorbrogger C ，Martinelli R ，Stone M ，Gniadek T ，Busch MP ... -  《-》

Limited Correlation between SARS-CoV-2 Serologic Assays for Identification of High-Titer COVID-19 Convalescent Plasma Using FDA Thresholds.

Larkey NE ，Ewaisha R ，Lasho MA ，Roforth MM ，Granger D ，Jerde CR ，Wu L ，Gorsh A ，Klassen SA ，Senefeld JW ，Joyner MJ ，Baumann NA ，Theel ES ，Mills JR ... -  《Microbiology Spectrum》

Neutralizing antibody levels against SARS-CoV-2 variants of concern Delta and Omicron in vaccine breakthrough-infected blood donors.

Novel SARS-CoV-2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID-19 convalescent plasma (CCP) a potential frontline treatment. In this study, we investigated the kinetics of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against VOCs Delta and Omicron in vaccine breakthrough infected plasma donors. Serum samples from 19 donors were collected at the time of plasma donation and tested for anti-SARS-CoV-2 nAbs (using live authentic VOC viral neutralization test) and IgG (Liaison® SARS-CoV-2 S1/S2 and Liaison® SARS-CoV-2 TrimericS IgG assays, DiaSorin). Measures were correlated with different variables, including the time between last vaccine dose and CCP donation, and time between SARS-COV-2 infection and CCP donation. nAb titers against VOC Delta and Omicron were directly related to the time interval since last vaccine dose to CCP donation, but inversely related to time since COVID19 breakthrough infection. SARS-CoV-2 breakthrough infection in vaccinated in donors boosts nAb titers against VOCs Delta and Omicron, but such titers decay shortly after infection. Therefore, CCP must be collected early after vaccine breakthrough infection.

Franchini M ，Focosi D ，Mengoli C ，Percivalle E ，Sammartino JC ，Ferrari A ，Zani M ，Glingani C ，Baldanti F ... -  《-》