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

Abstract

Highlights COVID-19 convalescent plasma (CCP) is widely used as a treatment. There are sufficient safety data. Data for a high level of evidence efficacy are lacking. Randomized controlled trials (RCT) published to date have several flaws and biases. Suggestions are provided for the next round of CCP RCTs.

Neutralising antibody escape of SARS‐CoV‐2 spike protein: Risk assessment for antibody‐based Covid‐19 therapeutics and vaccines

“…The nAbs isolated from SARS‐CoV‐2 patients are preferentially encoded by certain heavy‐chain germline genes and the two most frequently elicited antibody families (IGHV3‐53/3‐66 and IGHV1‐2) can each bind the RBS in two different binding modes 8 . The first nAb‐based manufactured therapeutic has been COVID19 convalescent plasma (CCP), whose efficacy seems promising 9 but for which randomised controlled trials are still pending 10 . Antiviral monoclonal nAb have entered the market, 11 and polyclonal IgG formulations (i.e., hyperimmune serum) will likely follow 12 .…”

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

“…There have been three different exploitations of nAbs. The most immediate has been COVID-19 convalescent plasma (CCP) [ 5 ], whose efficacy seems promising in the early disease course [ 6 ] but for which many randomized controlled trials are still pending [ 7 ]. Antiviral monoclonal nAbs have also entered the market for emergency use authorization (EUA) [ 8 ].…”

Development and Characterization of anti-SARS-CoV-2 Intravenous Immunoglobulin from COVID-19 Convalescent Plasma

“…Other studies demonstrate no improvement in hospitalized patients with COVID-19 [ 10 , 11 ]. There are several disadvantages associated with this treatment, such as the uncontrolled consistency of cytokines, blood clotting factors and other molecules that can worsen the condition of recipient patients [ 12 ]. Adverse effects can include allergy/anaphylaxis, transfusion-related acute lung injury, transfusion-associated circulatory overload, unintended infection and antibody-dependent enhancement [ 5 ].…”

“…In addition, the broad specificity of immunoglobulins against different isolates of infectious agents provides neutralizing benefits. Therefore, a hyperimmune anti-SARS-CoV-2 immunoglobulin G formulation produced from a large CCP pool could be effective against different isolates of SARS-CoV-2 in COVID-19 patients without the CCP-associated transfusion disadvantages [ 12 , 18 ]. Despite vaccines being the primary strategy in managing the ongoing COVID-19 pandemic, their effectiveness is limited for individuals with lymphopenia and primary/secondary antibody deficiencies.…”