Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights.

BACKGROUND: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years. METHODS: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA. RESULTS: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD). CONCLUSION: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Coronary artery calcifications and 6-month mortality in patients with COVID-19 without known atheromatous disease.

BACKGROUND: Coronary artery calcium (CAC) is an independent risk factor for major adverse cardiovascular events; however, its impact on coronavirus disease 2019 (COVID-19) mortality remains unclear, especially in patients without known atheromatous disease. AIMS: To evaluate the association between CAC visual score and 6-month mortality in patients without history of atheromatous disease hospitalized with COVID-19 pneumonia. METHODS: A single-centre observational cohort study was conducted, involving 293 consecutive patients with COVID-19 in Paris, France, between 13 March and 30 April 2020, with a 6-month follow-up. Patients with a history of ischaemic stroke or coronary or peripheral artery disease were excluded. The primary outcome was all-cause mortality at 6 months according to CAC score, which was assessed by analysing images obtained after the first routine non-electrocardiogram-gated computed tomography scan performed to detect COVID-19 pneumonia. RESULTS: A total of 251 patients (mean age 64.8±16.7 years) were included in the analysis. Fifty-one patients (20.3%) died within 6 months. The mortality rate increased with the magnitude of calcifications, and was 10/101 (9.9%), 15/66 (22.7%), 10/34 (29.4%) and 16/50 (32.0%) for the no CAC, mild CAC, moderate CAC and heavy CAC groups, respectively (p=0.004). Compared with the no calcification group, adjusted risk of death increased progressively with CAC: hazard ratio (HR) 2.37 (95% confidence interval [CI] 1.06-5.27), HR 3.1 (95% CI 1.29-7.45) and HR 4.02 (95% CI 1.82-8.88) in the mild, moderate and heavy CAC groups, respectively. CONCLUSIONS: Non-electrocardiogram-gated computed tomography during the initial pulmonary assessment of patients with COVID-19 without atherosclerotic cardiovascular disease showed a high prevalence of mild, moderate and heavy CAC. CAC score was related to 6-month mortality, independent of conventional cardiovascular risk factors. These results highlight the importance of CAC scoring for patients hospitalized with COVID-19, and calls for attention to patients with high CAC.

Hypocalcemia-induced seizure with Fahr's syndrome.

INTRODUCTION: Fahr's syndrome is a rare but severe brain complication of hypoparathyroidism and its consequences. CASE PRESENTATION: A 72-year-old female patient was hospitalized in intensive care unit after two generalized seizures along with a severe hypocalcemia, due to hypoparathyroidism following a thyroidectomy for benign nodules and poor compliance with calcium treatment with treatment due to cognitive disorders. Brain CT showed cortical atrophy and extensive bilateral symmetrical calcifications of the cerebellum, thalami and basal ganglia, typical of Fahr's syndrome. CONCLUSION: Nephrologists should be aware Fahr's syndrome in patients with hypoparathyroidism, it is associated with an increased risk of seizures. Thus, the control of calcemia in hypoparathyroidism is important, especially in patients with brain calcifications.