We compared the risk of severe COVID-19 during two periods 2021 and 2022 when Delta and Omicron, respectively, were the dominating virus variants in Scania county, Sweden. We adjusted for differences in sex, age, comorbidities, prior infection and vaccination. Risk of severe disease from Omicron was markedly lower among vaccinated cases. It was also lower among the unvaccinated but remained high (> 5%) for older people and middle-aged men with two or more comorbidities. Efforts to increase vaccination uptake should continue.

Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75–0.83) and 0.70 (95% CI 0.65–0.74), than qSOFA, AUC 0.70 (95% CI 0.66–0.75) and 0.62 (95% CI 0.57–0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.

Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had undergone NETosis in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl lewis^X present on salival mucins to L-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent NET release independent of elastase and NADPH-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by PMA. Furthermore, saliva/sialyl lewis^X mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet's disease prone to oral ulcers, failed to induce NETosis, but for different reasons, demonstrating that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.

Patients with Staphylococcus aureus bacteremia (SAB) at risk for infective endocarditis (IE) need to be identified since they should undergo echocardiography. We validate previous scoring systems for IE-risk determination, and evaluate if time to blood culture positivity (TTP) could improve scoring systems. This retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score, including TTP, was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA. 465 episodes with SAB were included in the derivation cohort of which 38 (8.2%) represented IE. Median TTP was significantly shorter in episodes with IE (8.7 IQR (7.7-10.6) hours) compared to those without (13.3 IQR (10.5-16.5) hours). Employing a cut-off at 13 hours, TTP had a sensitivity of 100% (CI, 91-100) and specificity of 52% (CI, 47-57) for IE. The POSITIVE score included TTP, intravenous drug use, embolisations and presence of preexisting heart conditions. It had a sensitivity of 93% (CI, 76-99) and a specificity of 70% (CI, 66-74) in the validation cohort. The performance of POSITIVE was superior to PREDICT and the specificity was higher than that of VIRSTA. TTP, either by itself, or as part of the POSITIVE score can be used to identify patients with SAB at low risk for IE. Further validation is needed as TTP is sensitive to several external factors.

We compared vaccine effectiveness against severe COVID-19 between December 2021 and March 2022 when Omicron BA.1 and BA.2 were the dominating SARS-CoV-2 variants in Scania county, Sweden. Effectiveness remained above 80% after the transition from BA.1 to BA.2 among people with at least three vaccine doses but the point estimate decreased markedly to 54% among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. Booster vaccination seems necessary to maintain sufficient protection.

Group B streptococcus (GBS) is a leading neonatal pathogen and a growing cause of invasive disease in the elderly, with clinical manifestations such as pneumonia and sepsis. Despite its clinical importance, little is known about innate immunity against GBS in humans. Here, we analyze the role of human group IIA secreted phospholipase A₂ (sPLA₂-IIA), a bactericidal enzyme induced during acute inflammation, in innate immunity against GBS. We show that clinical GBS isolates are highly sensitive to killing by sPLA₂-IIA but not by human antimicrobial peptides. Using transgenic mice that express human sPLA₂-IIA, we demonstrate that this enzyme is crucial for host protection against systemic infection and lung challenge by GBS. We found that acute sera from humans diagnosed with invasive GBS disease contain increased levels of sPLA₂-IIA compared with normal sera from healthy individuals, indicating that GBS induces an sPLA₂-IIA response in blood during human infection. We demonstrate that clinically relevant GBS strains are rapidly killed in these acute sera. We also demonstrate that the bactericidal effect is entirely due to sPLA₂-IIA, showing that sPLA₂-IIA might represent an important component of humoral innate immunity against GBS. Our data provide experimental and clinical evidence that sPLA₂-IIA protects humans against GBS infections.