Mbonde, Amir A.

Importance West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure Immunosuppresion. Main Outcomes and Measures Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

Abstract Background Despite the increasing incidence of neuroinvasive West Nile virus (NiWNV) infection in the US, the spectrum of disease characteristics and neuroimaging findings in immunosuppressed (IS) individuals are not adequately described. We aimed to compare the clinical characteristics and outcomes of NiWNV infection in IS and immunocompetent (IC) patients. Methods We extracted relevant data from all NiWNV patients hospitalized 7/2003-10/2021 at Mayo Clinic hospitals. Cohort was inclusive of patients from the recent historic WNV outbreak in Arizona in 2021. Chi-Square or Kruskal-Wallis and logistic regression were used to compare relevant variables and determine predictors of mortality respectively. Results We included 115 patients (72 IC and 43 IS), mean age 63.5 years; neurologic syndromes included meningoencephalitis (85.2%), encephalomyelitis (8.7%) and myeloradiculitis (6.1%). Presenting symptoms were malaise (72%), fever (66%), altered mentation (64%), gastrointestinal (47%) and myalgia (35.7%). MRI brain was abnormal in 62.8% (49/78), demonstrating T2/FLAIR hyperintensities in 47.4% (brainstem, thalamus, temporal lobes), leptomeningeal enhancement (16.7%) and diffusion restriction (20.5%). Altered mental status (76.7% vs 56.9%), myalgia (44.4% vs. 20.9%), myoclonus (18.6% vs. 4.2%) and thalamic MRI T2 FLAIR abnormalities (11.4% vs 0%) were more common in IS patients. Higher CSF WBC counts were observed in IC vs IS patients (P< 0.05). Immunosuppressed patients were more likely to be treated with intravenous immunoglobulin (44.2% vs 8.3% p=< 0.001) and/or interferon therapy (32.6% vs 6.9%, p=0.0003) and had increased odds of 90-day mortality on multivariable analysis (Adjusted Odds Ratio, AOR 2.22; 95% CI 1.065-4.627, p=0.0334). In the IS subgroup, ICU admission, mechanical ventilation, and Glasgow coma scale of < 8 were associated with reduced overall survival/increased 90-day mortality (p< 0.005). Conclusion Individuals presenting in summer/fall months with the aforementioned symptoms and/or MRI abnormalities should be evaluated for NiWNV infection. Compared to the immunocompetent, immunosuppressed patients with NiWNV are at a significantly greater mortality risk. Novel and effective antiviral therapies aimed at improving outcomes are warranted. Disclosures All Authors: No reported disclosures.

ABSTRACT. The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31–4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04–2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01–2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36–7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.

Introduction: Reversible cerebral vasonstriction syndrome (RCVS) is an increasingly recognized clinical and radiologic syndrome. However, it has been rarely reported in the setting of the novel coronavirus disease-2019 (COVID-19) infection or sarcomatous tumors. RCVS might be the initial manifestations of COVID-19 infection or noncatecholamine producing masses including sarcoma. Case Report: A 44-year-old male who developed COVID-19–related symptoms followed by rapid onset of severe headaches in the setting of persistently elevated blood pressure (BP). Brain imaging showed multifocal arterial narrowing in the anterior and posterior circulation consistent with RCVS. Serial imaging demonstrated resolution of the arterial narrowing after BP control was achieved with improvement in the patient’s headaches. Further investigation for secondary causes of the patient’s elevated BP revealed a right renal mass, and the patient underwent right nephrectomy, and the biopsy results confirmed the diagnosis of pleomorphic sarcoma. Conclusion: Our case suggests a possible association between severe acute respiratory syndrome coronavirus 2 with development of RCVS, but further studies are needed to validate this observation, establish a causal relationship and define a pathophysiological mechanism. Considering tumors other than catecholamine-producing masses as a potential risk factor for developing RCVS might lead to earlier detection and treatment of any underlying malignancy in patients whom the main and sole presentation could be RCVS.