This is a summary, written by members of the CITF Secretariat, of:

Ullah I, Beaudoin-Bussières G, Symmes K, Cloutier M, Ducas E, Tauzin A, Laumaea A, Bégin P, Mothes W, Kumar P, Bazin R, Finzi A, Uchil PD. The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice.
bioRxiv 2022.06.10.495677; doi:

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

Convalescent plasma therapy (CPT), which entails using plasma containing anti-SARS-CoV-2 antibodies taken from recovered individuals, has achieved mixed results in treating aged or immunosuppressed individuals suffering from severe COVID-19. In a preprint, not yet peer-reviewed, CITF funded researcher Dr. Andrés Finzi (Université de Montréal) and colleagues used an in vivo murine (mouse) model to ascertain the mechanisms by which COVID-19 convalescent plasma (CCP) may be more effective.

The specific characteristics of CCP samples that would be effective in controlling SARS-CoV-2 are complex and incompletely defined. Using in vivo imaging, the researchers discerned that convalescent plasma with robust Fc receptor-mediated activity Fc receptors control humoral and innate immunity in response to infections, as well as the prevention of chronic inflammation or auto-immune diseases. Fc receptors are found on the cells of the innate and adaptive immune system. They allow for antibodies to be captured by the cells which assists in their ability to kill the pathogen trapped by the antibody. can protect against SARS-CoV-2 infection, either as a therapy or as a preventative treatment, despite low neutralization capacity.

Key points:

  • High Fc-effector activity is a significant criterion in selecting convalescent plasma samples for therapeutic applications.
  • In an in vivo mouse model demonstrating high Fc-effector activity using CCP was more effective as a therapy, and to a reduced extent, was effective as a preventative measure against severe disease.
  • Aside from antibody neutralization activity, other mechanisms such as antibody-dependent cell cytotoxicity (ADCC) mediated by the Fc portion of the antibodies, are required to adequately identify the best CCP samples for therapeutic uses.
  • Despite its low antibody neutralization capacity against variants of concern, such as Delta or Beta, in some cases convalescent plasma may provide effective immunity, likely via these Fc-receptor mediated activities.
  • Despite neutralizing poorly, CCP samples devised from the original SARS-CoV-2 virus were able to delay mortality in mice infected by the Delta and Beta variants.

Thus, Fc-effector activity is a significant criterion for CCP selection for therapeutic applications.