The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

CTL combat intracellular pathogens by killing infected cells. The molecular targets of their attack are foreign peptides bound to self MHC encoded class I molecules. Immunization of mice with peptides containing CTL determinants was shown to elicit CD4-dependent CTL. Here, we have achieved in vivo CTL priming with naturally processed 8-10 amino acid long class I-restricted peptides emulsified in an adjuvant. A potent, reproducible and physiologically relevant response was obtained using peptides from an intracellular bacterium and five viruses (including HIV) in two murine MHC haplotypes. This method is suitable for multiple vaccination, since a 'cocktail' of peptides derived from three pathogens elicited effector CTL against each pathogen. Most importantly, peptide-induced CD8+CD4- CTL were CD4(+)-independent. These results have implications for CTL induction in situations where CD4 T cells are depleted or compromised, as is the case in HIV infection.

We investigated the effector mechanisms operating during the rejection of a transplantable solid lymphoma E.G7 (H-2b) which expresses the gene encoding chicken ovalbumin (OVA). Anti-OVA cytotoxic T lymphocytes (CTL) completely and specifically protected animals from the onset of, but could not eradicate established, E.G7 tumors. The growth of the same lymphoma was also effectively prevented by the antibody GK1.5, whose target molecule, CD4, was expressed on E.G7 cells in vivo. Furthermore, GK1.5 was able to eradicate established solid E.G7 tumors. GK1.5-mediated tumor elimination was due to its antitumor activity, and not to the elimination of regulatory CD4+ cells, based on unimpaired tumor growth in the absence of GK1.5 in animals that genetically lack CD4 T cells. In vitro, GK1.5 did not kill tumor cells: complement activation or apoptosis induction were not evident. In vivo, GK1.5-mediated tumor regression did not depend on natural killer cells, but it absolutely required CD8+ cells and intact Fcgamma receptor. We conclude that, in the E.G7 model, the collaboration of antibody and CTL immunity was crucial for the successful immunotherapy of established tumors. The mechanism of this collaboration is discussed.

Per the American Society for Apheresis, therapeutic plasma exchange (TPE) is a Category III indication in the management of immune thrombocytopenia (ITP). This nationally representative study evaluates TPE utilization in hospitalized adults with a primary admission diagnosis of ITP. Hospitalizations with ITP as the primary admitting diagnosis were analyzed from the 2010 to 2014 National Inpatient Sample, the largest all-payer inpatient database in the United States.Univariate and multivariable logistic regressions were used to determine clinical outcomes in ITP patients undergoing TPE. Sampling weights were applied to