Abstract
Studies on brain abscess are hampered by single-centre design with limited sample size and incomplete follow-up. Thus, robust analyses on clinical prognostic factors remain scarce.
This ...Danish nationwide, population-based cohort study included clinical details of all adults (≥18 years) diagnosed with brain abscess in the Danish National Patient Registry from 2007 through 2014 and the prospective clinical database of the Danish Study Group of Infections of the Brain covering all Danish departments of infectious diseases from 2015 through 2020. All patients were followed for 6 months after discharge. Prognostic factors for mortality at 6 months after discharge were examined by adjusted modified Poisson regression to compute relative risks with 95% confidence intervals (CI).
Among 485 identified cases, the median age was 59 years interquartile range (IQR 48–67) and 167 (34%) were female. The incidence of brain abscess increased from 0.4 in 2007 to 0.8 per 100 000 adults in 2020. Immuno-compromise was prevalent in 192/485 (40%) and the clinical presentation was predominated by neurological deficits 396/485 (82%), headache 270/411 (66%), and fever 208/382 (54%). The median time from admission until first brain imaging was 4.8 h (IQR 1.4–27). Underlying conditions included dental infections 91/485 (19%) and ear, nose and throat infections 67/485 (14%), and the most frequent pathogens were oral cavity bacteria (59%), Staphylococcus aureus (6%), and Enterobacteriaceae (3%). Neurosurgical interventions comprised aspiration 356/485 (73%) or excision 7/485 (1%) and was preceded by antibiotics in 377/459 (82%). Fatal outcome increased from 29/485 (6%) at discharge to 56/485 (12%) 6 months thereafter. Adjusted relative risks for mortality at 6 months after discharge was 3.48 (95% CI 1.92–6.34) for intraventricular rupture, 2.84 (95% CI 1.45–5.56) for immunocompromise, 2.18 (95% CI 1.21–3.91) for age >65 years, 1.81 (95% CI 1.00–3.28) for abscess diameter >3 cm, and 0.31 (95% CI 0.16–0.61) for oral cavity bacteria as causative pathogen. Sex, neurosurgical treatment, antibiotics before neurosurgery, and corticosteroids were not associated with mortality.
This study suggests that prevention of rupture of brain abscess is crucial. Yet, antibiotics may be withheld until neurosurgery, if planned within a reasonable time period (e.g. 24 h), in some clinically stable patients. Adjunctive corticosteroids for symptomatic perifocal brain oedema was not associated with increased mortality.
In a nationwide population-based cohort study of 485 adults diagnosed with brain abscess, Bodilsen et al. report that abscess rupture, immunocompromise, age, and abscess diameter >3 cm were independent risk factors for mortality. Withholding antibiotics until neurosurgery and use of adjunctive corticosteroids were safe in selected patients.
To investigate whether there is a dose-dependent association between empiric dexamethasone and outcome in viral meningitis.
Observational cohort study of adults hospitalised for viral meningitis, ...both with and without a microbiologically confirmed diagnosis, in Denmark between 2015-2020. Dose-dependent associations between dexamethasone (one dose=10 mg) and an unfavourable outcome (Glasgow Outcome Scale score 1-4) at 30 days after discharge were assessed with weighted logistic regression. Entropy balancing was used to compute weights.
Of 1,025 included patients, 658 (64%) did not receive dexamethasone, 115 (11%) received 1-2 doses, 131 (13%) received 3-4 doses, and 121 (12%) received ≥5 doses. Among patients treated with dexamethasone, the median number of doses was higher for those without an identified pathogen than for those with a microbiologically confirmed viral aetiology (5 IQR 3-8 vs 3 IQR 2-5; p<0.001). Using no doses of dexamethasone as reference, the weighted odds ratios (OR) for an unfavourable outcome were 0.55 (95% CI 0.29-1.07) for 1-2 doses, 1.13 (95% CI 0.67-1.89) for 3-4 doses, and 1.43 (95% CI 0.77-2.64) for ≥5 doses. In the subgroup of enteroviral meningitis, the weighted OR was 3.08 (95% CI 1.36-6.94) for ≥5 doses but decreased to 2.35 (95% CI 0.65-8.40) when the reference group was restricted to patients treated with antibiotics for suspected bacterial meningitis.
This study showed no dose-dependent association between dexamethasone and an unfavourable outcome in patients with viral meningitis. In enteroviral meningitis, ≥5 doses were associated with an increased risk of an unfavourable outcome. However, a sensitivity analysis indicated that the association was affected by unmeasured or residual confounding by severity.
Abstract
Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined.
This nationwide population-based ...prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1–4) 30 days after discharge were examined by modified Poisson regression.
In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27–44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression 32/162 (20%) and shingles 90/149 (60%) were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3–7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60–358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95–1.88) for enteroviruses, 1.55 (95% CI 1.00–2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98–2.33) for varicella-zoster virus and 1.37 (95% CI 0.61–3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03–1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
In a nationwide study of 1066 Danish adults with viral meningitis, Petersen et al. report that incomplete recovery persists in one in five patients 30 days after discharge. Female patients in particular have an increased risk of an unfavourable outcome, whereas the type of virus is not associated with the prognosis.
OBJECTIVETo test the hypothesis that enterovirus meningitis (EM) is a frequent and self-limiting condition, the epidemiology of EM in adults was examined. METHODSUsing a prospective, nationwide, ...population-based database, all adults with EM confirmed by PCR of the CSF from 2015 to 2019 were included. Unfavorable outcome was defined as Glasgow Outcome Scale scores of 1-4 at discharge. Modified Poisson regression was used to compute adjusted relative risks (RRs). RESULTSA total of 419 cases of EM in 418 adults (46% female, median age 31 years interquartile range (IQR) 27-35) yielded an incidence of 1.80/100,000/year. Admission diagnoses included CNS infection 247/397 (62%), other neurologic conditions 89/397 (22%), and cerebrovascular diseases 33/397 (8%). Genotype was available for 271 cases, of which echovirus 30 accounted for 155 (57%). Patients presented with headache 412/415 (99%), history of fever 303/372 (81%), photophobia 292/379 (77%), and neck stiffness 159/407 (39%). Fever (≥38.0°C) was observed in 192/399 (48%) at admission. The median CSF leukocyte count was 130 106/L (range 0-2,100) with polymorphonuclear predominance (>50%) in 110/396 (28%). Cranial imaging preceded lumbar puncture in 127/417 (30%) and was associated with non-CNS infection admission diagnoses and delayed lumbar puncture (median 4.8 hours IQR 3.4-7.9 vs 1.5 IQR 0.8-2.8, p < 0.001). Unfavorable outcome occurred in 99/419 (24%) at discharge; more often in female patients (RR 2.30 1.58-3.33) and less frequent in echovirus 30 (RR 0.67 0.46-1.00) in adjusted analyses. Outcome remained unfavorable in 22/379 (6%) after 6 months. CONCLUSIONSEM is common among young, healthy adults. Although the long-term prognosis remains reassuring, a substantial proportion have moderate disability at discharge, especially female patients.
To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and the durability of vaccine-induced antibodies.
Adults without history of SARS-CoV-2 infection ...from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase 4 study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90, and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 after first vaccination. Nondurable vaccine response was defined as day-90 responders who no longer had significant responses by day 180.
Of 6544 participants completing two vaccine doses (median age 64 years; interquartile range: 54–75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by an mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hyporesponsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG and 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type, and number of comorbidities were associated with all four outcomes. Additionally, age ≥75 years was associated with hyporesponsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds ratio: 1.59; 95% confidence interval: 1.25–2.01) but not for Spike IgG.
Comorbidity, male sex, and vaccine type were risk factors for hyporesponsiveness and nondurable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-second-vaccination levels for most individuals after 6 months.
Abstract
Background
Oral cavity bacteria are the most frequent etiology of brain abscess. Yet, data on the clinical presentation and outcome are scarce.
Methods
We performed a nationwide, ...population-based study comprising all adults (aged ≥18 years) with brain abscess due to oral cavity bacteria in Denmark from 2007 through 2020. Prognostic factors for unfavorable outcome (Glasgow outcome scale, 1–4) were examined using modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals (CIs).
Results
Among 287 identified patients, the median age was 58 years (interquartile range, 47–66), and 96 of 287 (33%) were female. Preexisting functional impairment was absent or mild in 253 of 280 (90%), and risk factors for brain abscess included immunocompromise in 95 of 287 (33%), dental infection in 68 of 287 (24%), and ear–nose–throat infection in 33 of 287 (12%). Overall, a neurological deficit was present in 246 of 276 (86%) and in combination with headache and fever in 64 of 287 (22%). Identified microorganisms were primarily the Streptococcus anginosus group, Fusobacterium, Actinomyces, and Aggregatibacter spp., and 117 of 287 (41%) were polymicrobial. Unfavorable outcome occurred in 92 of 246 (37%) at 6 months after discharge and was associated with antibiotics before neurosurgery (RR, 3.28; 95% CI, 1.53–7.04), rupture (RR, 1.89; 95% CI, 1.34–2.65), and immunocompromise (RR, 1.80; 95% CI, 1.29–2.51), but not with specific targeted antibiotic regimens. Identified dental infection was associated with favorable prognosis (RR, 0.58; 95% CI, .36–.93).
Conclusions
Brain abscess due to oral cavity bacteria often occurred in previously healthy individuals without predisposing dental infections. Important risk factors for unfavorable outcome were rupture and immunocompromise. However, outcome was not associated with specific antibiotic regimens supporting carbapenem-sparing strategies.
Brain abscess due to oral cavity bacteria often occurs in healthy individuals for unknown reasons with high risks of unfavorable outcome. Important prognostic factors include rupture of brain abscess and immunocompromise. Targeted antibiotic regimen was not associated with outcome.
People with human immunodeficiency virus (PWH) may be at increased risk of several respiratory syndromes including chronic obstructive pulmonary disease (COPD). In matched cohort studies, we examined ...risk factors for COPD in PWH and their parents and siblings compared with population controls.
Using data from national registries, competing risk regression models were constructed and used to calculate adjusted hazard ratios (aHRs) for COPD. We evaluated the effect of human immunodeficiency virus characteristics, smoking, and educational attainment on COPD incidence in PWH.
A total of 226 PWH and 1029 population controls were diagnosed with COPD during 63 661 and 562 171 person-years of follow-up. PWH had increased risk of being diagnosed with COPD compared to controls (aHR, 2.02 95% confidence interval, 1.75-2.33). Parents and siblings of PWH were also more likely to be diagnosed with COPD compared to controls. CD4+ T-cell counts were not associated with COPD, but unsuppressed viral replication, smoking status, and educational attainment were associated with COPD in PWH. No COPD diagnoses were registered in PWH with high educational attainment and absence of smoking.
PWH have an increased risk of being diagnosed with COPD, as have their parents and siblings. This seems to be driven primarily by smoking and low socioeconomic status.
SARS‐CoV‐2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients ...might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long‐term SARS‐CoV‐2 infection with the pre‐VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi‐species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS‐CoV‐2 among immunocpromised patients.
Within a year of the SARS-CoV-2 pandemic, vaccines inducing a robust humoral and cellular immune response were implemented worldwide. However, emergence of novel variants and waning vaccine induced ...immunity led to implementation of additional vaccine boosters.
This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2 vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection naïve at the time of their first vaccine dose. Proportions of SARS-CoV-2 Spike-specific T cells were determined after each vaccine dose using the Activation Induced Markers (AIM) assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay.
We found a significant increase in SARS-CoV-2 Spike-specific CD4+ and CD8+ T cell responses following the third dose of a SARS-CoV-2 mRNA vaccine as well as enhanced CD8+ T cell responses after the fourth dose. Further, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone.
Our findings highlight the boosting effect on T cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T cell immunity although with reduced levels in the elderly.
