Background: Knowledge of the epidemiology and clinical characteristics of varicella zoster virus (VZV) encephalitis remains limited. Methods: Nationwide prospective cohort study of adults treated for microbiologically confirmed VZV encephalitis at Danish departments of infectious diseases from 2015 to 2019. Modified Poisson regression analysis was used to compute adjusted relative risks (RRs) of unfavorable outcome. Results: We identified 92 adults (49% female) with VZV encephalitis, yielding an incidence of 5.3/1 000 000 per year (95% CI, 4.2–6.6). Median age was 75 years (IQR, 67–83) and immunocompromising conditions were frequent (39%). Predominant symptoms were confusion (76%), headache (56%), nausea (45%), gait disturbance (42%), and personality changes (41%). Cranial imaging showed cerebral vasculitis (including infarction and hemorrhage) in 14 (16%) patients and encephalitic abnormalities in 11 (13%) with predilection for the brainstem and deep brain structures. Intravenous acyclovir treatment was initiated a median (IQR) of 13.4 hours (5.2–46.3) since admission, while cranial imaging and lumbar puncture were performed after 6.3 hours (2.5–31.0) and 18.5 hours (4.9–42.0). In-hospital, 1-month, and 3-month mortalities were 4%, 9%, and 11%, respectively. Unfavorable outcome (Glasgow Outcome Score of 1–4) was found in 69% at discharge, with age (adjusted RR [aRR], 1.02; 95% CI, 1.01–1.03), vasculitis (aRR, 1.38; 95% CI, 1.02–1.86), and Glasgow Coma Scale (GCS) <15 (aRR, 1.32; 95% CI, 1.01–1.73) identified as independent risk factors. Conclusions: VZV encephalitis occurs primarily in elderly or immunocompromised patients with a higher incidence than previously estimated. The diagnosis is often delayed; risk factors for unfavorable outcome are age, cerebral vasculitis, and GCS <15.

Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Background: Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood. Methods: In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51–72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections. Results: We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified. Conclusions: SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.

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.