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Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.

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are reported in Supplementary Table 2. Of all participants in the immunogenicity subcohort, 50.4% were ≥60 years old, 51.7% were considered at-risk for severe COVID-19 (defined as having one or more comorbidities associated with elevated risk of severe COVID-19 1 ) and 44.8% had been assigned female sex at birth. At US sites, 49.3% had minority status (defined as other than White Non-Hispanic). The immunogenicity subcohort was 26.0% from Latin America, 23.9% from South Africa and 50.0% from the United States. Supplementary Tables 3-5 provide demographics and clinical characteristics of the immunogenicity subcohort by geographic region.

Biofilm-related infections are considered a major cause of morbidity and mortality in hospital environments. Biofilms allow microorganisms to exchange genetic material and to become persistent colonizers and/or multiresistant to antibiotics. Corynebacterium pseudodiphtheriticum (CPS), a commensal bacterium that colonizes skin and mucosal sites has become progressively multiresistant and responsible for severe nosocomial infections. However, virulence factors of this emergent pathogen remain unclear. Herein, we report the adhesive properties and biofilm formation on hydrophilic (glass) and hydrophobic (plastic) abiotic surfaces by CPS strains isolated from patients with localized (ATCC10700/Pharyngitis) and systemic (HHC1507/Bacteremia) infections. Adherence to polystyrene attributed to hydrophobic interactions between bacterial cells and this negatively charged surface indicated the involvement of cell surface hydrophobicity in the initial stage of biofilm formation. Attached microorganisms multiplied and formed microcolonies that accumulated as multilayered cell clusters, a step that involved intercellular adhesion and synthesis of extracellular matrix molecules. Further growth led to the formation of dense bacterial aggregates embedded in the exopolymeric matrix surrounded by voids, typical of mature biofilms. Data also showed CPS recognizing human fibrinogen (Fbg) and fibronectin (Fn) and involvement of these sera components in formation of "conditioning films". These findings suggested that biofilm formation may be associated with the expression of different adhesins. CPS may form biofilms in vivo possibly by an adherent biofilm mode of growth in vitro currently demonstrated on hydrophilic and hydrophobic abiotic surfaces. The affinity to Fbg and Fn and the biofilm-forming ability may contribute to the establishment and dissemination of infection caused by CPS.

Background: Non-HACEK Gram-negative bacilli (NGNB) infective endocarditis (IE) has a growing frequency. We aimed to describe cases of NGNB IE and find associated risk factors. Methods: We conducted a prospective observational study of consecutive patients with definitive IE according to the modified Duke criteria in four institutions in Brazil. Results: Of 1154 adult patients enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 years, males predominated, accounting for 25/38 (65.8%). Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). Worsening heart failure occurred in 18/38 (47.4%). Higher prevalence of embolic events was found (55,3%), mostly to the central nervous system 7/38 (18.4%). Vegetations were most commonly on aortic valves 17/38 (44.7%). Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38 (34.2%). Overall mortality was 19/38 (50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), hemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors for mortality. Conclusions: The rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with central venous catheters, prosthetic valves, intracardiac devices and hemodialysis and had a high mortality rate.

BackgroundThe aim of this study is to describe the clinical characteristics of patients with infective endocarditis (IE) due to non-HACEK Gram-negative bacilli (NGNB) and the risk factors associated with mortality in a large multicentre cohort.MethodsThis prospective observational study included consecutive patients with definitive IE diagnosed according to the modified Duke criteria in Brazil between 2006 and 2019. Patients with blood or heart valve cultures positive with NGNB were identified and studied.ResultsOf 1154 adult patients with definite IE enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 (IQR, 43-69) years. Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). IE was associated with a higher prevalence of embolic events 21/38(72.4%). Chronic renal failure 18/38(44.7%), prosthetic valves 19/38(50%) and device-related IE 6/8(15.8%) were common. Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38(34.2%). Overall mortality was 19/38(50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), haemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors associated with mortality, but not multidrug-resistant microorganisms.ConclusionsThe rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with the presence of central venous catheters, prosthetic valves, intracardiac devices and haemodialysis and had a high mortality rate.

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