Prevalence of HEV infection in acute non-ABC hepatitis and prognostic role of extrahepatic manifestations.

Background: HEV-3 and HEV-4 are emerging cause of zoonotic acute hepatitis in high-income countries. In Europe the disease is underdiagnosed but hyperendemic areas have been identified. We describe a population with acute non-ABC (n-ABC) hepatitis in Abruzzo, the Italian region with the highest seroprevalence reported. The study was included in the surveillance of acute hepatitis E by the Italian Institute of Public Health started in 2004 and implemented in 2015. Methods: Patients with n-ABC hepatitis during 2004-2018 in all Abruzzo Infectious Disease Departments were tested for HEV-IgM (Wantai®) and HEV-RNA (ORF3). Positive samples were sequenced (Beckman Coulter®) and phylogenetic tree (MEGA 6.06 software) obtained. Clinical data were retrospectively collected and an alimentary risk factors-questionnaire was administered. Categorical and quantitative variables were compared (Chi square test or Fisher test and Wilcoxon test). Results: 97 hospitalized patients were tested, most cases (91.7%) after 2015. Overall, HEV-IgM resulted positive in 36% and HEV-RNA detectable in 33.3%. All 24 sequences obtained were HEV-3, with two small groups of closely related strands. L'Aquila was the Province with higher positivity rate (44%). Retrospective clinical data were acquired in 86.5% of patients, no one having liver failure. Higher ALT-levels (1282.34 vs 893.25, p=0.0139) and extrahepatic symptoms (OR 16.69, p=0.0018) were strongly associated with HEV-IgM presence. Two small outbreaks are described. Conclusions: More than one third of n-ABC hepatitis in all Abruzzo are HEV-related. Extrahepatic symptoms correlate with HEV aetiology. Implementing surveillance is mandatory to really understand the extent of the disease.

Hepatitis E Outbreak in the Central Part of Italy Sustained by Multiple HEV Genotype 3 Strains, June-December 2019.

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.

Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: data from two Italian COVID-19 units.

The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of imaging findings, depending on disease severity and time course. We conducted a retrospective evaluation of hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement, in order to identify relationships between clinical, serological, imaging data and disease outcomes in patients with COVID-19. Clinical and serological records of patients admitted to two COVID-19 Units of the Abruzzo region in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively evaluated. Sixty-one patients (22 females and 39 males) of median age 65 years were enrolled. Fifty-six patients were discharged while death occurred in 5 patients. None of the lung abnormalities detected by CT was different between discharged and deceased patients. No differences were observed in the features and extent of pulmonary involvement according to age and gender. Logistic regression analysis with age and gender as covariates demonstrated that ferritin levels over the 25th percentile were associated with the involvement of all 5 pulmonary lobes (OR = 14.5, 95% CI 2.3-90.9, p = 0.004), the presence of septal thickening (OR = 8.2, 95% CI 1.6-40.9, p = 0.011) and the presence of mediastinal lymph node enlargement (OR = 12.0, 95% CI 1.1-127.5, p = 0.039) independently of age and gender. We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender and not associated with disease outcomes. The identification of reliable biomarkers in patients with COVID-19 may help guiding clinical decision, tailoring therapeutic approaches and ultimately improving the care and prognosis of patients with this disease.

A "One-Health" approach for diagnosis and molecular characterization of SARS-CoV-2 in Italy.

The current pandemic is caused by a novel coronavirus (CoV) called SARS-CoV-2 (species Severe acute respiratory syndrome-related coronavirus, subgenus Sarbecovirus, genus Betacoronavirus, family Coronaviridae). In Italy, up to the 2nd of April 2020, overall 139,422 confirmed cases and 17,669 deaths have been notified, while 26,491 people have recovered. Besides the overloading of hospitals, another issue to face was the capacity to perform thousands of tests per day. In this perspective, to support the National Health Care System and to minimize the impact of this rapidly spreading virus, the Italian Ministry of Health involved the Istituti Zooprofilattici Sperimentali (IZSs), Veterinary Public Health Institutes, in the diagnosis of SARS-CoV-2 by testing human samples. The Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise is currently testing more than 600 samples per day and performing whole genome sequencing from positive samples. Sequence analysis of these samples suggested that different viral variants may be circulating in Italy, and so in Abruzzo region. CoVs, and related diseases, are well known to veterinarians since decades. The experience that veterinarians operating within the Public Health system gained in the control and characterization of previous health issues of livestock and poultry including avian flu, bluetongue, foot and mouth disease, responsible for huge economic losses, is certainly of great help to minimize the impact of this global crisis.