Abstract
Pneumonia, coronavirus disease 2019
DISEASE PROGRESSION, CORONAVIRUS DISEASE 2019, DISEASE, PNEUMONIA, CYTOTOXICITY, CORONAVIRUS, SEVERE ACUTE RESPIRATORY SYNDROME

Convalescent plasma (CP) treatment of coronavirus disease 2019 (COVID-19) has shown significant therapeutic effect when administered early (eg, Argentinian trial showing reduced hospitalization) but has in general been ineffective (eg, REMAP-CAP trial without improvement during hospitalization). To investigate whether the differences in CP used could explain the different outcomes, we compared neutralizing antibodies, anti-spike IgG, and avidity of CP used in the REMAP-CAP and Argentinian trials and in convalescent vaccinees. We found no difference between the trial plasmas, emphasizing initial patient serostatus as treatment efficacy predictor. By contrast, vaccinee CP showed significantly higher titers and avidity, being preferable for future CP treatment.
Outcomes of 2 clinical SARS-CoV-2 convalescent plasma treatment trials, one effective the other ineffective, were not explained by serological markers of the convalescent plasma used. Start of treatment in relation to disease progression was likely the key factor that determined success.Despite successful development of targeted antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need for more effective treatment options for severely affected individuals and better protection for vulnerable groups, such as the immunocompromised. While immune protection relies on both cellular and humoral immunity, the administration of SARS-CoV-2–specific neutralizing antibodies (nAb) can enhance host immunity. Convalescent plasma (CP) treatment using plasma collected from previously infected donors has been shown to have a significant therapeutic effect in terms of disease progression when administered early or before hospitalization [As the clinical trials differ in patient demographics, treatment protocols, and timing in relation to the course of coronavirus disease 2019 (COVID-19), the reasons underlying the differences in efficacy of CP remain to be determined. Firstly, potential variability in the criteria used to select donors may influence CP potency. It is also possible that CP administration is only able to change the course of disease during very early stages, mimicking the role of vaccination, whereas this protective effect might be lost if administered after onset of the host's own response. In addition, assays used in CP characterization, which determine selection of high-titer antisera for transfusion, may vary between trials. High titers of nAb against SARS-CoV-2 are generally considered essential for protection, while some other antibody properties, such as afucosylation or association with antibody-dependent cellular cytotoxicity, have been considered potentially harmful [In this study, we have investigated whether the differences in nAb titers, spike protein binding, and avidity of plasma used in the Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP) and Argentinian trials were associated with their markedly different clinical outcomes [