ABSTRACT
Background: Blood product in therapeutic transfusion are now commonly acknowledged to present biologically active constituents during processes of preparation. In the midst of worldwide COVI-19 pandemic, preliminary evidence, suggest that convalescent plasma may lessen the severity of COVID-19, particularly concerning patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms. Aim(s): This study examined the influence of photochemical pathogen reduction treatment (PRT) using amotosalen-HCl and UVA light vs untreated control convalescent plasma (n = 72 -paired samples) -cFFP. Method(s): This study investigated the soluble inflammatory factors: SCD40L, IFN-alpha, IFN-beta, IFN-gamma, IL-1 beta, IL-6, IL-8, IL-10, IL-18, TNF-alpha and ex-vivo inflammatory bioactivity on endothelial cells. Result(s): We observed that IL-8 concentrations were significantly decreased in cFFP w PRT, whereas IL-18 concentration was increased. We observed after activation with cFFP w PRT and w/o PRT no significant modulation of IL-6 released by endothelial cells. CD54 and CD31 expression in the presence of cFFP (w or w/o PRT) is close to negative controls, even if CD54 and CD31 were significant decreased in presence of cFFP w vs w/o PRT. Conclusion(s): It appears valuable to carry on investigations, of IL-18 and IL-8, on both the physiopathology of PRT convalescent plasma treated and post marketing clinical trials. Further research, including a careful clinical evaluation of CCP-treated patients, will be required to further define the clinical relevance of these findings.
ABSTRACT
Background: COVID-19 convalescent plasma (CCP) contains neutralizing anti-SARS- CoV- 2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Aim(s): Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients. Method(s): CCP (n = 766) were compared to control non-convalescent plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralizing auto-Ab to type I IFNs, and reported adverse events in the recipients. Result(s): CCP exhibited significantly higher IL-6 and TNF-alpha (0.531+/-0.04 vs 0.271+/-0.04;p = 0.0061 and 0.900+/-0.07 vs 0.283+/-0.07 pg/ml;p < 0.0001), respectively) and lower IL-10 (0.731+/-0.07 vs 1.22+/-0.19 pg/ ml, p = 0.0034) levels than control plasma. Other inflammatory markers as well as ex-vivo bioactivity did not differ significantly between CCP and control plasma. Neutralizing auto-Abs against type I IFNs were detected in 14/766 (1.8 %) CCP. They were not associated with reported adverse events when transfused (n = 14). Inflammatory markers and bioactivity in CCP with or without auto-Ab, or in CCP associated or not with adverse events in transfused patients, did not differ significantly. Overall, CCP exhibited moderately increased inflammatory markers compared to control plasma with no discernable differences in ex-vivo bioactivity. Auto-Ab to type I IFNs, detected in a small fraction of CCP, were not associated with reported adverse events or differences in inflammatory markers. Conclusion(s): Further defining the clinical relevance of these findings will require further studies including careful clinical evaluation of patients treated with CCP.