Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
Objective: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department. Design: Prospective, international multicenter, convenience sample study. Setting: Four general emergency departments at academic centers in Sweden, Switzerland, and Canada. Patients: All emergency encounters among adults where one of the following criteria were fulfilled: respiratory rate >25 breaths per minute; heart rate >120 beats per minute; altered mental status; systolic blood pressure <100 mm Hg; oxygen saturation <90% without oxygen; oxygen saturation <93% with oxygen; reported oxygen saturation <90%. Intervention: None. Measurements and Main Results: A total of 524 emergency department patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a noninfectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 h, 54 patients (10%) were admitted to an intensive care unit, and 23 patients (4%) died within 72 h. For the primary outcome, detection of infected-related organ dysfunction within 72 h, the area under the receiver operating curve (AUC) for HBP was 0.73 (95% CI 0.68–0.78) among all patients and 0.82 (95% CI 0.76–0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12–24 h) HBP had an AUC of 0.87 (95% CI 0.79–0.95) among all patients and 0.88 (95% CI 0.77–0.99) among patients confidently adjudicated to either infection or noninfection. Conclusions: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.
BackgroundErysipelas is a common and severe infection where the aetiology and optimal management is not well-studied. Here, we investigate the clinical features, bacteriological aetiology, and treatment of erysipelas.MethodsEpisodes of erysipelas in a seven-years period in our institution were studied retrospectively using a pre-specified protocol and is presented with descriptive and comparative statistics.Results1142 episodes of erysipelas were identified in 981 patients. Patients had a median age of 61 years, 59 % were male, a majority had underlying diseases or predisposing conditions, and the leg was most often affected. Wound cultures were taken in 343 episodes and 56 grew group A streptococci (GAS), 53 grew group G streptococci (GGS), 11 grew group C streptococci (GCS), and 153 grew Staphylococcus aureus. Blood cultures were drawn in 49 % of episodes and 50 cultures were positive with GGS as the most common finding (21 cultures) followed by GAS in 13, group B streptococci in 5, S. aureus in 4, and GCS in 3 cultures. In 45 % of episodes, patients received antibiotics with activity against S. aureus.ConclusionsGGS is the most common streptococcus isolated in erysipelas and the role of S. aureus in erysipelas remains elusive.
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