The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice

• DOI: 10.1016/j.xcrm.2022.100893
• Publication Date: 2022-12-29T20:33:31Z
• Authors: Irfan Ullah; Guillaume Beaudoi...; Kelly Symmes; Marc Cloutier; Eric Ducas; Alexandra Tauzin; Annemarie Laumaea; Michael W. Grunst; Katrina Dionne; Jonathan Richard; Philippe Bégin; Walther Mothes; Priti Kumar; Renée Bazin; Andrés Finzi; Pradeep D. Uchil
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; Treatment Outcome; SARS-CoV-2; Immunoglobulin G; Animals; COVID-19; Article; COVID-19 Serotherapy; 3. Good health

COVID-19 convalescent plasmas (CCPs) are chosen for plasma therapy based on neutralizing titers and anti-Spike immunoglobulin levels. However, CCP characteristics that promote SARS-CoV-2 control are complex and incompletely defined. Using an in vivo imaging approach, we demonstrate that CCPs with low neutralizing (ID50 ≤ 1:250), but moderate to high Fc-effector activity, in contrast to those with poor Fc function, delay mortality and/or improve survival of SARS-CoV-2-challenged K18-hACE2 mice. The impact of innate immune cells on CCP efficacy depended on their residual neutralizing activity. Fractionation of a selected CCP revealed that IgG and Ig(M + A) were required during therapy, but the IgG fraction alone sufficed during prophylaxis. Finally, despite reduced neutralization, ancestral SARS-CoV-2-elicited CCPs significantly delayed Delta and Beta-induced mortality suggesting that Fc-effector functions contribute to immunity against VOCs. Thus, Fc activity of CCPs provide a second line of defense when neutralization is compromised and can serve as an important criterion for CCP selection.