Vascular contribution to cognitive impairment and dementia (VCID) is a clinical label encompassing a wide range of cognitive disorders progressing from mild to major vascular cognitive impairment (VCI), which is also defined as vascular dementia (VaD). VaD diagnosis is mainly based on clinical and imaging findings. Earlier biomarkers are needed to identify subjects at risk to develop mild VCI and VaD. In the present meta-analysis, we comprehensively evaluated the role of inflammatory biomarkers in differential diagnosis between VaD and Alzheimer’s disease (AD), and assessed their prognostic value on predicting VaD incidence. We collected literature until January 31, 2021, assessing three inflammatory markers [interleukin(IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α] from blood or cerebrospinal fluid (CSF) samples. Thirteen cross-sectional and seven prospective studies were included. Blood IL-6 levels were cross-sectionally significantly higher in people with VaD compared to AD patients (SMD: 0.40, 95% CI: 0.18 to 0.62) with low heterogeneity (I2: 41%, p = 0.13). Higher IL-6 levels were also associated to higher risk of incident VaD (relative risk: 1.28, 95% CI: 1.03 to 1.59, I2: 0%). IL-6 in CSF was significantly higher in people with VaD compared to healthy subjects (SMD: 0.77, 95% CI: 0.17 to 1.37, I2: 70%), and not compared to AD patients, but due to limited evidence and high inconsistency across studies, we could not draw definite conclusion. Higher blood IL-6 levels might represent a useful biomarker able to differentiate people with VaD from those with AD and might be correlated with higher risk of future VaD.

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Background Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. Objectives The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. Methods The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. Results The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. Conclusions COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.

The members of human Herpesviridae family are fully acknowledged as pathogenic agents in immunocompromised individuals, often responsible for a number of severe diseases. On the other hand, in immunocompetent hosts, Herpesviridae-related infections typically display an asymptomatic or paucisymptomatic course, sometimes manifesting with flu-like symptoms. However, such infections can occasionally cause organ damage or multisystemic involvement in healthy subjects. Herein, we describe the first case of a simultaneous co-infection by five different Herpesviridae family members in an apparently immunocompetent young subject. A 30-year-old Caucasian man presented to our medical unit with colitis. During hospitalization, he developed multi-organ damage involving heart, pancreas and liver. Quantitative polymerase chain reaction analysis showed positive results for cytomegalovirus, Epstein-Barr virus, human herpes virus 6, human herpes virus 7, and human herpes virus 8. Remission of clinical manifestations and complete negativization of viral load were achieved by antiviral therapy. To the best of our knowledge, such simultaneous infection by multiple herpesviruses causing a severe multi-organ dysfunction has never been described in patients with preserved immune function. Careful literature review showed that organ damage in immunocompetent subjects was reported in very few cases of co-infection by two herpesviruses, and in only one case of co-infection by three herpesviruses. Multi-organ damage in our patient likely resulted from additional effects induced by Epstein-Barr virus, human herpes virus 6, human herpes virus 7, and human herpes virus 8, through either a superinfection occurring after initial cytomegalovirus disease, or a simultaneous co-infection of the different viral agents. Moreover, the possibility of a transient and partial immune dysfunction, predisposing the patient to develop a severe herpesvirus-associated disease, cannot be completely ruled out. Although a formal indication to antiviral therapy has not been established in herpesvirus-infected immunocompetent individuals, our case supports the usefulness of such therapy in case of severe multisystemic clinical manifestations. This original case report suggests that the possibility of multiple herpesvirus simultaneous infections should be taken into account in differential diagnosis for severe organ dysfunction, also in apparently immunocompetent subjects.

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