Merete Storgaard

Inborn errors of type I interferon (IFN-I) immunity account for ∼7–8% of herpes simplex encephalitis (HSE) cases in young children, but the pathogenesis of HSE in adults is largely unknown. We report that IFN-I autoantibodies (auto-Abs) in serum/plasma samples drawn before, during, or after HSE in 16/339 Danish adults neutralized 0.1–10 ng/ml of IFN-I. Neutralization was IgG-mediated and was also detected in cerebrospinal fluid in several patients. Patients’ serum impaired the ability of exogenous IFN-I to protect fibroblasts against herpes simplex virus (HSV)-1 infection in vitro. Among patients with neutralizing IFN-I auto-Abs, a larger fraction were HSV-1 IgG seronegative, suggesting that these auto-Abs confer a greater risk of HSE during primary HSV-1 infection. Neutralization was mainly driven by auto-Abs to IFN-ω, and the risk of HSE in adults with auto-Abs was significantly elevated (odds ratio [OR] = 3.1 for IFN-ω and OR = 2.0 for any IFN-I) compared with the general population. Overall, auto-Abs neutralizing IFN-I accounted for ∼5% of adult HSE cases.

Background: This study was performed to investigate the clinical characteristics and outcome of patients with herpes simplex (HSV) type 1 encephalitis. Methods: Nationwide, prospective, population-based cohort study using the Danish Study Group for Infections of the Brain database to identify all adults hospitalized with microbiologically confirmed HSV-1 encephalitis from 2015 to 2023 in Denmark. Modified Poisson regression was used to estimate the relative risk (RR) with 95% confidence intervals (CI) for 6-month mortality, adjusted for age, sex, immunocompromise, altered mental status, imaging abnormalities, time to acyclovir (>6 hours from admission), and pathogen. Analysis of acyclovir delay >6 hours was repeated post-hoc using time after lumbar puncture as reference. Results: A total of 154 patients with confirmed HSV-1 encephalitis were included, yielding a mean annual incidence of 0.36/100.000. Frequent symptoms at admission included a history of fever (in 101/128 [79%]) and confusion (in 99/154 [78%]). The median times from admission to lumbar puncture and acyclovir treatment were 21 (interquartile range, 6–70) and 24 (7–74) hours, respectively. The adjusted RR for 6-month mortality was 1.15 (95% CI, 0.39–3.41) for acyclovir initiation >6 hours after admission and 1.06 (95% CI, 1.004–1.13) for each day of delay after admission. The adjusted RR of 6-month mortality was 1.85 (95% CI, 1.01–3.45) for delayed acyclovir treatment of >6 hours since lumbar puncture. Anti N-Methyl-D-aspartate receptor encephalitis was diagnosed in 9/154 (6%) of patients after HSV-1 encephalitis. Conclusions: Early recognition of HSV-1 encephalitis remains challenging, and the condition is associated with high mortality. Delayed acyclovir treatment, especially following lumbar puncture, was associated with increased risks of fatal outcome.

Advances in coronavirus disease 2019 management has led to decreases in disease burden; however, immunocompromised patients continue to experience prolonged or persistent infections. We investigated immunological factors associated with time to viral clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunocompromised patients. By integrating clinical follow-up data, SARS-CoV-2-specific humoral and cellular response data, and single-cell RNA transcriptomic data, we uncovered differential immune responses between patients exhibiting short or long time-to-clearance (TTC), both at diagnosis and later during infection. We found that prolonged infection was associated with reduced SARS-CoV-2-specific humoral responses (P = 0.035) and diminished development of CD4+ and CD8+ T-cell activation (P = 0.045 and P = 0.038, respectively) despite levels of interferon-γ-producing T cells not being negatively affected. Baseline transcriptional profiles revealed increased immunological engagement of CD8+ cytotoxic T and natural killer (NK) cells among patients with prolonged TTC, potentially to compensate for impaired functional T-cell activation. Differential gene expression further pointed towards features of impaired T-cell functionality and exhaustion as contributors to prolonged TTC, including enrichment of NEAT1, CD52, and IL12RB2 in Long TTC patients. Our findings indicate that impaired viral clearance in some immunocompromised patients reflects an actively engaged yet dysregulated immune response. This underscores the complexity of immune dysfunction in this population and highlights the need for targeted interventions to restore effective, antiviral immunity, with a particular focus on regaining functional activation of antigen-specific T cells.

HIV-related stigma remains a major barrier to improving the lives of people with HIV (PWH) and curbing the epidemic globally. This cross-sectional study assessed HIV-related stigma, based on The HIV Stigma Framework, among PWH in Denmark, and examined its potential associations with sociodemographic characteristics, as well as with HIV-related, psychosocial and sexual health measures. Data from 630 participants (486 men and 144 women) in the SHARE study—a nationwide survey on psychosocial and sexual health among PWH in Denmark conducted from 2021 to 2022—were analysed using sex-stratified linear and logistic regression models adjusted for relevant confounders. Results showed that anticipated stigma was the most commonly reported stigma mechanism, with 68% of men and 77% of women expressing high levels of concern about HIV status sharing. In contrast, enacted stigma was reported by 9% of men and 22% of women. The multivariate regression analyses revealed that higher stigma levels were associated with originating from low- or middle-income countries and with a history of mental health problems, whereas non-heterosexual identity and a longer time since HIV diagnosis were linked to lower stigma. In both men and women, stigma was significantly associated with fewer close friends, loneliness, anxiety and reduced sexual desire. Among men, stigma was also significantly associated with sharing one’s HIV status with fewer people, depression, suicidal tendencies and erectile dysfunction. In conclusion, HIV-related stigma, notably stigma related to anticipated stigma, remains prevalent among PWH in Denmark and it is significantly associated with a range of psychosocial and sexual challenges.

Background: Uncertainty about the role of neurosurgery in brain abscess treatment is reflected in surveys and observational studies. Methods: This was a nationwide population-based cohort study of all adults (≥18 years) diagnosed with brain abscess in Denmark from 2007 until 2023. Inverse probability weighting was applied to balance covariates according to neurosurgical treatment strategy. Outcomes included risks of mortality, rupture, and unfavorable outcome (Glasgow Outcome Scale score 1–4) 6 months after discharge and were assessed using modified Poisson and Cox regression with 95% confidence intervals (CIs). Unbalanced covariates were included in regression models for doubly robust estimations. Results: The cohort comprised 558 patients (median age, 59 [interquartile range, 49–69] years; 367/558 [66%] male). A nonoperative strategy was assigned to 234 of 558 (42%) and neurosurgery to 324 of 558 (58%). Predisposing meningitis, diameter, and deep location of abscess were included in doubly robust estimations. Analyses of treatment strategy showed that a nonoperative approach was associated with adjusted relative risks (95% CIs) of 2.47 (1.50–4.04) for mortality, 2.25 (1.26–4.01) for rupture, and 1.24 (.95–1.61) for unfavorable outcome compared with neurosurgery. Additionally, 85 of 234 (36%) patients assigned to the nonoperative strategy required subsequent neurosurgery. Compared with neurosurgery at any time, maintained nonoperative treatment was associated with adjusted hazard rate ratios (95% CIs) of 1.53 (.84–2.76) for mortality, 2.00 (1.17–3.42) for rupture, and 1.62 (1.12–2.34) for unfavorable outcome. Conclusions: Nonoperative strategy was associated with twice the risks of mortality and rupture, and one-third of patients required subsequent neurosurgery. These results support recommendations for neurosurgical drainage of brain abscess.

Bone health is an emerging concern in the aging human immunodeficiency virus (HIV)-infected population. We aimed to investigate bone mineral density (BMD) and bone microarchitecture in persons living with HIV (PLHIV). The study was a cross-sectional study. BMD and bone microarchitecture were investigated by Dual-Energy X-ray Absorptiometry (DXA) at the hip and lumbar spine and High-Resolution peripheral Quantitative Computed Tomography (HRpQCT) at the radius and tibia. Information about risk factors for fracture was obtained from a questionnaire. 183 PLHIV were included, 160 (131 males, 29 females) completed the visit. Age range was 30–78 years and the mean time since first HIV-positive serology was 16.5 years. 47% had low bone density and 6% had osteoporosis. The mean T-score by DXA was − 1.2 (standard deviation (SD) ± 1.0), − 0.7 (SD ± 0.9), and − 0.7 (SD ± 1.3) at the femoral neck, total hip and lumbar spine, respectively. We observed no significant difference in BMD by DXA between participants below or above age 50. BMI was significantly lower in PLHIV with lower BMD (p = 0.001, ANOVA). HRpQCT measurements showed significant differences in cortical area, volumetric BMD, and most microarchitecture parameters between PLHIV with BMD in the normal, low, and osteoporotic ranges measured at the tibia and radius. Our results indicate that bone microarchitecture and BMI vary considerably between PLHIV with normal, low, and osteoporotic BMD. These differences may partly explain the increased fracture risk seen in PLHIV. Trial numbers : Ethics Committee of the Central Denmark Region (case no. 1-10-72-238-17), Danish Data Protection Agency (case no. 1-16-02-708-17).

Objective: To describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes.Methods: A population‐based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes.Results: In total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased odds of preterm birth, small for gestational age or low birth weight. First‐trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23–11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13–9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes.Conclusions: Pregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and NRTI + PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors.

To the Editor,In a recent report in this journal, risk factors for recurrence of tuberculosis (TB) were identified [1]. By multivariate logistic regression, authors found diabetes, weight gain ≤ 5%...