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.

The occurrence of paravalvular abscesses in the course of an acute endocarditis of the aortic valve indicates an advanced stadium of the disease. The infection has spread beyond the limits of the valve leaflets, and ongoing destruction of the paravalvular tissue is to be expected, if the endocarditis is continually treated by antibiotics alone. Surgery of acute endocarditis with paravalvular abscess, however, supposedly carries an increased risk of early mortality and late morbidity. The following prospective study was carried out to determine whether a radical surgical approach together with aggressive postoperative antibiotic therapy could help to improve results. Between 1988 and 1995, 138 patients were operated during the acute phase of infective endocarditis; in 102 the aortic valve was involved. Among these, 44 had paravalvular abscesses at the time of surgery. The mean age of both groups was the same, but there was a higher rate of concomitant coronary artery disease, multiple valve involvement, advanced NYHA-class, and staphylococcal disease among the patients with abscesses. All interventions were carried out with cardiopulmonary bypass and cardioplegic arrest. The aortic valve was resected, abscesses were removed, and each part of potentially infected or necrotic tissue was resected as complete as possible, irrespective of the possibility to jeopardize the conduction system or to create large tissue defects. The aortic valve was replaced with a mechanical prosthesis in each case. The postoperative antibiotic regimen was specifically directed against the microorganisms isolated preoperatively; therapy was only modified, if signs of systemic infection did not disappear three days after surgery. The operative mortality was 10% among patients without an abscess and 11% in patients with a paravalvular abscess. Early recurrent endocarditis was recorded in two patients without and in only one patient with an abscess. Late recurrent endocarditis was noted in three patients; none of them had abscesses at the time of surgery. We conclude that the operative risk of acute endocarditis of the aortic valve with a paravalvular abscess does not have to be inevitably higher compared to cases without paravalvular involvement. To achieve these results, it is necessary to use a radical surgical approach and to adjust postoperative antibiotic therapy, if infectious signs do not disappear shortly after surgery.

With a rising incidence of COVID-19–associated morbidity and mortality worldwide, it is critical to elucidate the innate and adaptive immune responses that drive disease severity. We performed longitudinal immune profiling of peripheral blood mononuclear cells from 45 patients and healthy donors. We observed a dynamic immune landscape of innate and adaptive immune cells in disease progression and absolute changes of lymphocyte and myeloid cells in severe versus mild cases or healthy controls. Intubation and death were coupled with selected natural killer cell KIR receptor usage and IgM+ B cells and associated with profound CD4 and CD8 T-cell exhaustion. Pseudo-temporal reconstruction of the hierarchy of disease progression revealed dynamic time changes in the global population recapitulating individual patients and the development of an eight-marker classifier of disease severity. Estimating the effect of clinical progression on the immune response and early assessment of disease progression risks may allow implementation of tailored therapies.

BACKGROUND: Current regulations do not require blood collection facilities to ask donors about cigarette smoking, and the prevalence of nicotine and its metabolites in blood products is not well established. Although smokers have higher hemoglobin (Hb) levels, smoking may adversely affect the quality of donated red blood cells through higher carboxyhemoglobin (COHb) content and premature hemolysis.From the