What is the optimal usage of coronavirus disease 2019 convalescent plasma donations?

Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline

“…3 However, higher hopes have been raised from the efficacy signals obtained with convalescent plasma (CP) therapy, 4 where the active substances are assumed to be polyclonal neutralizing antibodies (nAb). The interpretation of trials on CP efficacy has been largely hampered by the lack of standardized doses and poor assessment of nAb with viral neutralization tests; 5 nevertheless, favorable preliminary results have led immediately to research and development of pharmaceutical-grade hyperimmune sera 6 and mAbs ( Figure 1). These mAbs have several obvious advantages over CP and immune sera ( Table 1), given that the number of therapeutic antibodies is restricted to one or two per treatment: (a) selection of the most potent candidates (with IC 50 or the more reliable 7,8 IC100 parameter in the subnanomolar to low picomolar range); (b) better assessment of the therapeutic dose per body weight; c) exclusion of the so-called antibody-dependent enhancement (ADE) phenomenon.…”

The Road towards Polyclonal Anti-SARS-CoV-2 Immunoglobulins (Hyperimmune Serum) for Passive Immunization in COVID-19

“…Several countries have begun to direct CCP donations towards plasma manufacturers [ 9 ], to investigate CCP fractionation resulting in polyclonal IgG formulations. Polyclonal IgG can be administered intravenously (IVIg), intramuscularly or, more rarely, intranasally.…”

The art of the possible in approaching efficacy trials for COVID19 convalescent plasma

“…In SARS, 5 mL/kg of plasma at a titer ≥1:160 was utilized ( Cheng et al, 2005 ). Such titer needs to be specified through the viral neutralization assay (VNT), thus obviating any bias from the use of diverse surrogate tests having poor correlation with the VNT ( Focosi et al, 2020a , Focosi et al, 2020b , Focosi et al, 2020c ). Additionally, given the fast-declining kinetics of nAb titers, the VNT should be assessed on each donated unit in the case of repeated donations, rather than assuming the same value across multiple donations.…”

“…The data available suggest that late stage disease (ICU admission/ventilator support) is unlikely to respond to CCP therapy ( Agarwal et al, 2020 ), with several authors suggesting an optimal window as short as 44 h post-hospitalization for transfusing CCP ( Salazar et al, 2020a , Salazar et al, 2020b ). It is a well-known phenomenon that nAb titer correlates with the severity of symptoms in COVID-19 patients ( Focosi et al, 2020a , Focosi et al, 2020b , Focosi et al, 2020c ) and preliminary reports suggested that CCP was only effective in early stage disease ( Focosi et al, 2020a , Focosi et al, 2020b , Focosi et al, 2020c ), thus trials targeting late treatment in severe patients are unlikely to produce useful insights. Limiting RCTs to early stage disease, despite the limitations imposed on the modality, should allow a higher probability of success.…”

“…Other variables may be investigated, including antibody isotyping and IgG subclasses ( Focosi et al, 2020a , Focosi et al, 2020b , Focosi et al, 2020c ), but the abovementioned six points deserve major attention. Pathogen reduction technologies cause a decline of nAb titers which varies according to the platform used ( Kostin et al, 2020 ) and can be missed if using surrogate tests ( Tonn et al, 2020 ).…”