Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. This retrospective multicentre study (2015–2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020–2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4

Emergence of azole-resistant Aspergillus fumigatus represents a concern for public health worldwide. Here we applied a spatial analysis to a large number of records on A. fumigatus azole resistance in the Netherlands to evaluate the relationship of a set of environmental factors with the emergence of resistant isolates and to identify the potential risk areas. A total of 1850 aspergillosis cases were included in the analysis: 1559 caused by wild-type (WT) and 291 by azole-resistant (RES) strains. High-resolution maps containing environmental variables (climate, crop cultivations) were used as layers for spatial analysis. QGIS software was used for transformation and calculation of layers, and visualizing maps, whereas MaxEnt software was used to perform spatial analysis. A separate distribution map for WT and RES was generated using each layer, then the ratio between RES and WT suitability was calculated, and a new map was generated showing the areas where suitability of RES was higher than WT (ratio > 1). Layers presenting areas with a ratio > 1 were then used for a further analysis including all these layers together to generate a final risk map, to identify the most contributing environmental variables, and to estimate the number of people potentially exposed to the risk. Results showed that the areas with the highest RES/WT ratio were associated with the following variables: legume cultivations ratio 1.5–2.7; fruit tree plantations, ratio 2.1; dump sites and artificial sites, ratio 2.3–2.7; spring minimum and mean temperatures, ratio 1.6–1.8. Areas with medium, high, and very high risk covered a surface of about 2330 km2 and people exposed were >319,000, with Zeeland and Noord-Holland being the provinces with the highest risk. All together these results suggest that azole-resistance emergence is a complex phenomenon depending on a multitude of environmental variables that are not yet been fully explored.

Aspergillus fumigatus is a common fungus which has gained attention due to its resistance to azole compounds, substances used in both medical and agricultural settings. One of the genetic alterations responsible for this resistance is the mutation TR34/L98H in the cyp51A gene. The aim of this study was to understand the impact of azoles and non-azoles on Aspergillus fumigatus. By examining clinical samples, soil samples, and compost material, this research aims to provide insights into the susceptibility of these strains to antifungal substances. To deepen our understanding of the factors potentially involved in antifungal resistance, we combined in vitro studies of sixteen compounds against Aspergillus fumigatus with results from the sequencing of the cyp51 gene. We observed that compounds generally displayed a similar pattern activity against wild-type Aspergillus fumigatus. Non-azoles, except Pyrisoxazole and Amisulbrom, did not show any activity against Aspergillus fumigatus, while azole compounds displayed differential activity against the fungus, except for Tetraconazole. For the mutant strains, a generally similar activity was observed in both clinical and environmental samples, likely due to the same mutation in all the isolates. The implications of these findings may be relevant for better understanding the relationship between Aspergillus fumigatus and its ability to develop resistance to antifungal substances.

Abstract Background Hepatitis E virus (HEV) is the agent of hepatitis E, an emerging public-health infection with an increasing incidence in Europe. Due to the apparent lack of species barriers, HEV is considered a zoonotic agent, with swine as the main reservoir. This study investigated HEV prevalence in humans and domestic pigs in Northern Italy, a highly anthropic area with the highest pig farm density, to gain insights into the risk of HEV transmission from swine to humans. Methods A total of 508 blood samples were collected from blood donors (341 males and 167 females; from 18 to 66 years old) and from 1619 pigs in 40 different farms. Serological analyses were performed with ELISA to detect anti-HEV antibodies. In addition, 120 faecal pool samples collected from the pig farms with the highest seroprevalence and 69 salami produced in the same area were analysed to detect viral genome by Real-time PCR. Results In humans, HEV seroprevalence was 4.9% (CI95% 0.03-0.07); positive donors were mainly males, with seroprevalence increasing up to 12% (CI95% 0.09-0.15) in the 46-55 age group. Seroprevalence in swine was 53.00% (CI95% 0.50-0.55), with HEV detected in only 1% (CI95% 0.001-0.045) faeces. All food samples tested negative. Conclusions Even if the seroprevalence in pigs highlighted that HEV was actively circulating in the farms, the low seroprevalence in humans, the scarce HEV detection in swine faeces, and the absence in food products suggested that HEV transmission via faecal-oral or foodborne routes is unlikely, probably due to the implementation of severe biosecurity measures and high standards of hygiene in swine farms, and the continuous assessment of the critical points in the pig supply chain (from farm to fork). The serological surveillance of humans and the monitoring of farmed animals are needed to support the competent authorities in timely managing public health issues, improving human health and veterinary safety from a One Health perspective. Key messages • In the human-swine interface is important to monitor HEV presence. • The One Health approach is essential to control zoonotic diseases.

Pancreatic cancer (PC) represents the 6th cause of cancer death. Although the aetiology of PC is not completely understood, numerous risk factors have been identified in association with this cancer, among them diet. However, little is known about the association between the Mediterranean Diet (MedDiet) and the risk of PC. For this reason, we conducted a systematic review with meta-analysis according to the PRISMA guidelines, searching on three databases (PubMed/MEDLINE, Scopus, and EMBASE). The protocol was registered in PROSPERO. Both fixed and random effect models were performed. The Effect size was reported as a hazard ratio (HR) with a 95% Confidence Interval (CI). A total of eight articles were included. The methodological quality of the included meta-analyses was high. Our results show that a higher adherence to the MedDiet is associated with a lower risk of PC [HR:0.82 (0.76–0.88) p < 0.001, based on 1,301,320 subjects]. The results were also confirmed in sensitivity and subgroups analyses (avoidance of potential overlapping effects, type of tools used to assess dietary intake and the diagnosis of PC, prevalence and incidence of PC risk, country where the studies took place, sex, and cancer site). Promoting a higher adherence to the MedDiet could be an effective approach to reduce the risk of PC.

Background Numerous reports of resistance to terbinafine in Trichophyton spp. from all over the world are arousing justified attention and concern. Point mutations in the gene that encodes the squalene epoxidase (SQLE) enzyme are responsible for these therapeutic resistances.Objectives Primary objective of the study was to describe first isolates of Trichophyton spp. resistant to terbinafine among the patients treated between September 2019 and June 2022 at the Dermatology Units of Ospedale Maggiore Policlinico and San Bortolo Hospital. Secondary objective was to study the resistance mechanism.Methods Patients with confirmed Trichophyton spp. infection has been treated with systemic and topical terbinafine. Patients were then re-evaluated 12 weeks after the therapy. Patients with incomplete or absent response to terbinafine underwent a new skin scraping for direct mycological examination, new identification of dermatophyte species from culture and MALDI-TOF, molecular species identification, antifungal susceptibility testing and molecular analysis of SQLE gene.Results We identified five patients without clinical response to treatment with terbinafine. The DNA sequencing of the ITS region identified one Trichophyton rubrum and four Trichophyton indotineae. The T. rubrum strain showed minimum inhibitory concentration (MIC) (90% growth inhibition) of 4 mg/L for terbinafine. The four T. indotineae strains showed a MICs range of 0.25-4 mg/L for terbinafine. The analysis of the SQLE gene in the T. rubrum strain showed a nucleotide substitution generating a missense mutation (L393F). The SQLE gene sequencing in the T. indotineae strains showed a nucleotide substitution generating a missense mutation (F397L) in two strains, a nucleotide substitution L393S in one strain and a nucleotide substitution F415C in another strain.Conclusions We report the first cases of terbinafine-resistant Trichophyton isolates in the Italian population. Solid antifungal management programs will be needed to promote more responsible use of antimycotics and preserve their therapeutic efficacy to control antifungal resistance.

Fungal diseases correlated to beach sand or water have not yet been demonstrated due to the lack of epidemiological studies. This study aims to illustrate the fungal population in beach sands of the two largest Italian lakes and in sands and waters of Mediterranean coasts of Southern Italy to contribute to the identification and assessment of causes of microbiological pollution that might impair bathers health. A great difference was observed between the two lakes, where the total of colony-forming units (CFU) ranged from 33.3 to 1049.9 CFU/g. For coastal sands, the total CFU ranged from 216.7 to 538.8 CFU/g, and for coastal waters the total ranged from 185 to 368.7 CFU/ml. The survey revealed the prevalence of opportunistic pathogenic moulds, mainly Aspergillus spp. (A. niger and A. fumigatus) and Penicillium spp., both in freshwater and costal bathing sites. Dermatophytes and yeasts were not detected in the freshwater sands while they were found at low load in coastal waters (3.3 CFU/ml) and sands (1.7 CFU/g). Differences were observed between urban and non-urban coastal beaches with regard to isolation of dermatophytes only from one urban beach. The present study reports a great diversity of fungi in sand and water of bathing beaches confirming that the Mediterranean region has a greater variety of fungal species.

Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0–93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis.

The present study employed data collected during the Mycosands survey to investigate the environmental factors influencing yeasts and molds distribution along European shores applying a species distribution modelling approach. Occurrence data were compared to climatic datasets (temperature, precipitation, and solar radiation), soil datasets (chemical and physical properties), and water datasets (temperature, salinity, and chlorophyll-a concentration) downloaded from web databases. Analyses were performed by MaxEnt software. Results suggested a different probability of distribution of yeasts and molds along European shores. Yeasts seem to tolerate low temperatures better during winter than molds and this reflects a higher suitability for the Northern European coasts. This difference is more evident considering suitability in waters. Both distributions of molds and yeasts are influenced by basic soil pH, probably because acidic soils are more favorable to bacterial growth. Soils with high nitrogen concentrations are not suitable for fungal growth, which, in contrast, are optimal for plant growth, favored by this environment. Finally, molds show affinity with soil rich in nickel and yeasts with soils rich in cadmium resulting in a distribution mainly at the mouths of European rivers or lagoons, where these metals accumulate in river sediments.

Vaccination is the most effective way to control and prevent acute and chronic hepatitis B, including cirrhosis and HCC, on a global scale. According to WHO recommendations, 190 countries in the world have introduced hepatitis B vaccination into their national childhood immunization programs with an excellent profile of safety, immunogenicity, and effectiveness. Following vaccination, seroprotection rates are close to 100% in healthy children and over 95% in healthy adults. Persistence of anti-HBs is related to the antibody peak achieved after vaccination. The peak is higher the longer the antibody duration is. Loss of anti-HBs does not necessarily mean loss of immunity since most vaccinated individuals retain immune memory for HBsAg and rapidly develop strong anamnestic responses when boosted. Evidence indicates that the duration of protection can persist for at least 35 years after priming. Hence, booster doses of vaccines are currently not recommended to sustain long-term immunity in healthy vaccinated individuals. In Italy, vaccination against hepatitis B is met with success. In 2020, Italy became one of the first countries in Europe to be validated for achieving the WHO regional hepatitis B control targets.

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives The present study employed data collected during the Mycosands survey to investigate the environmental factors influencing yeasts and molds distribution along European shores by applying a species distribution modeling approach. Methods Occurrence data were compared to climatic datasets (temperature, precipitation, and solar radiation), soil datasets (chemical and physical properties), and water datasets (temperature, salinity, and chlorophyll concentration) downloaded from web databases. All dataset layers were edited and formatted by QGIS software and analyses were performed by MaxEnt software. Results The distribution maps inferred comparing occurrence data on shores for Aspergillus spp., Aspergillus fumigatus, A. flavus, A. niger, Fusarium spp., dematiaceous fungi, and considering all molds, to climatic datasets showed the highest probability of presence along Eastern and South-Central Mediterranean coasts, whereas comparison of water occurrence data to water features identified a high suitability along Eastern Mediterranean coasts, Gulf of Lion, Southern coasts of Spain, and Southern and Central Atlantic coast of Portugal, Southern Atlantic coast of France, Netherlands coasts, the mouth of Danube, coasts of the Ireland sea, and Kuri Lagoon in Lithuania. The main variables contributing to the models were minimum temperatures in winter, water temperature during spring, and chlorophyll concentration. The comparison with soil datasets showed a high tolerance of soils with a high concentration of CaCO3 and basic pH. Nitrogen concentration was tolerated at values below 1 g/kg and phosphorus concentration at values <20 mg/kg and >40 mg/kg. In addition, the model identified a high tolerance to soils rich in nickel. The same analyses were performed for the following groups of occurrence data: Candida spp., Rhodotorula spp., and all yeasts. Results showed the highest probability of presence on shores located along the coasts of Eastern Mediterranean Sea, Southern-Central Mediterranean Sea, Northern Adriatic Sea coasts, Kuri Lagoon, and Northern European coasts from France to Denmark. In waters, high suitability areas were located along the coasts of Northern Black Sea, Northern Adriatic Sea, coasts of Ireland Sea, Western Atlantic coast of France, and the Northern European coasts from France to western Denmark. The most relevant variables contributing to the model were minimum temperatures during winter and water chlorophyll concentration. The comparison with soil features showed similar results to those obtained for molds, except a high tolerance for soils rich in cadmium. Conclusions All together our results suggest a different probability of distribution of yeasts and molds along European shores. Yeasts seem to tolerate low temperatures better during winter than molds and this reflects a higher suitability for the Northern European coasts. This difference is more evident considering suitability in waters. Both distributions of molds and yeasts are influenced by basic soil pH, probably because acidic soils are more favorable to bacterial growth. Soils with high nitrogen concentrations are not suitable for fungal growth, which, in contrast, are optimal for plant growth, favored by this environment. Finally, molds show affinity with soil rich in nickel and yeasts with soils rich in cadmium resulting in a distribution mainly at the mouths of European rivers or lagoons, where these metals accumulate in river sediments.

Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives In Italy, a prevalence of 16.9% of resistance to clinical azoles was observed among Aspergillus fumigatus isolates from an agricultural environment. This spread of azole-resistance is attributed to the widespread use of 14a-demethylase inhibitors (DMIs). The aims of the present study were to investigate: the DMIs resistance in Italian A. fumigatus strains of clinical and environmental origin, both susceptible and resistant to clinical azoles; the molecular mechanism of resistance in strains susceptible to clinical azoles but resistant to at least one of the tested DMIs; the in vitro DMI resistance induced by prolonged exposure to DMIs in susceptible clinical and environmental strains, and the molecular mechanism of resistance. Methods A total of 54 A. fumigatus strains were selected: 23 susceptible to clinical azoles (CAS) and 31 resistant (CAR) with and without mutations in the CYP51A gene (TR34/L98H, F219I, G54R, G54E, D269Y, M220I, or F46Y/M172V/N248T/D255E/E427K). Antifungal susceptibility testing was performed for 8 DMIs (tebuconazole, epoxiconazole, difenoconazole, propiconazole, tetraconazole, flusilazole, fenbuconazole, and prochloraz) using broth microdilution method according to EUCAST and CLSI methods. Mutations in CYP51A, CYP51B, and HMG1 genes were investigated in CAS with DMI high MIC values. In vitro induction of resistance was performed using the 8 DMIs on 11 (6 clinical and 5 environmental) A. fumigatus strains susceptible both to clinical azoles and DMIs. A suspension of 106 conidia was inoculated on glucose-yeast extract-peptone agar plates containing different DMIs at different concentrations and incubated at 37°C for 72 h for six repeated passages. Results Comparable results were obtained using EUCAST and CLSI methods. Resistance (MIC ≥16) to tetraconazole and fenbuconazole was observed in 100% of isolates, both CAR and CAS. On the contrary, a statistically significant difference in tebuconazole, epoxiconazole, difenoconazole, propiconazole, and flusilazole MICs between CAR strains and CAS strains was observed with higher geometric means (GM) in CAR (range 4.9-9.3 mg/L) than in CAS (1.5-2.7 mg/L) strains. Prochloraz showed the lowest GMs: 0.6 and 0.25 mg/L in CAR and CAS strains, respectively. A significant difference of the GMs for all the DMIs tested, except prochloraz, was observed between the isolates harboring a TR34/L98H or a M220I mutation (GM range 10.4-16 mg/L) and those with other CYP51A mutations (GM range 1-4.6 mg/L). In the CAS showing high DMI MICs, the absence of CYP51A mutations was confirmed, while a synonymous mutation P394P, was identified in CYP51B. No mutations in HMG1 gene were found. In the induction tests, the prolonged exposure to DMIs showed an induced phenotypic resistance of 100% (11/11 isolates) for epoxiconazole, of 72.7% (8/11) for propiconazole, of 54% (6/11) for tebuconazole and difenoconazole, and of 9.1% (1/11) for prochloraz. Molecular analysis to understand if the phenotypic resistance corresponds to induced mutations in CYP51A, CYP51B, and HMG1 genes is in progress. Conclusions Preliminary results confirm cross-resistance between clinical azoles and DMIs, with MIC differences between CAR and CAS and between strains with different mutations in the CYP51A gene. Furthermore, the ability of DMIs to induce resistance in vitro was highlighted.

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BACKGROUND:Preventing and reducing nosocomial infections is a public health goal. Concern about healthcare-associated fungal infections has increased in recent years due to the emergence and spread of new pathogens, increasing antifungal resistance and outbreaks in hospital settings. AIM:To investigate the presence of medically relevant fungal species on environmental surfaces in 12 intensive care units of eight hospitals in Milan, Italy. METHODS:Environmental samplings, using contact plates on surfaces near bed stations and medical workstations, were conducted between November 2019 and January 2020. Fungi isolated were identified, and some were tested in vitro for antifungal susceptibility. FINDINGS:In total, 401 environmental samples were collected from 61 bed stations and 17 medical workstations. Positive samples were found in all hospitals except one, with positivity rates ranging from 4% to 24.2%. Filamentous fungi were found mainly on infusion pumps (23.2%) and patient tables (21.2%), whereas yeasts were found mainly on computers (25%) and floors (10.9%). Fungi were isolated from 12% of total samples. Filamentous fungi, mainly Aspergillus fumigatus, grew in 70.8% of positive samples, and yeasts grew in 27.1%, mainly Candida parapsilosis (42.8%) and Candida glabrata (28.6%). Fungi were detected near patients' beds and on surfaces at workstations, indicating potential for environment-to-patient, patient-to-patient and healthcare worker-to-patient transmission. CONCLUSIONS:Surveillance in hospital settings through environmental sampling may be an important component of fungal infection prevention.

An 82-year-old man had a diagnosis of prostate cancer and underwent curative radiotherapy. During the oncological follow-up, the patient showed biochemical relapse and underwent whole-body Cu-64-prostate-specific membrane antigen PET/CT for restaging purpose. Cu-64-prostate-specific membrane antigen PET/CT showed a pathological uptake in left iliac venous axis, subsequently confirmed as venous thrombosis.

BACKGROUND: hepatitis A is an infective disease whose global diffusion appears to be variable and strictly related to socioeconomic status, hygiene conditions, and access to potable water. During last twenty years, Italy registered a constant decrease of new cases with recurrent epidemic outbreaks. OBJECTIVES: to outline the hepatitis A epidemiological situation in Italy in the five-year period 2015-2019. DESIGN: descriptive study based on cases reported to the National Surveillance System for Acute Viral Hepatitis (SEIEVA). SETTING AND PARTICIPANTS: hepatitis A cases reported to SEIEVA from 2015 to 2019. MAIN OUTCOME MEASURES: hepatitis A incidence, percentages of cases exposed to known risk factors, distribution of cases by vaccination status. RESULTS: during the whole observational period, SEIEVA registered 4,929 type A hepatitis cases. The epidemic curve initially showed a trend with a low incidence level interrupted in August 2016 with the onset of a large epidemic, in the period between August 2016 and December 2017, involving 3,428 cases mostly adult men exposed to homosexual intercourses (MSM). Since January 2018, the trend of the cases has been decreasing even though its level is still higher than the pre-epidemic period. Based on the ana- lysis of the epidemic curve, three periods characterized by different trends in the monthly number of notified cases were identified: January 2015-July 2016 (pre-epidemic period), August 2016-December 2017 (epidemic period), January 2018-December 2019 (post-epidemic period). In the last observation period, cases show different charac- teristics compared to the previous periods. They are mainly males under 18 years (p=0.026), subjects travelling to Mo- rocco (8.9% vs 15.9%; p< 0.001) or being in contact with an infected person (p<0.001). The multivariate analysis confirmed a significantly higher probability for cases no- tified in the post-epidemic period, compared to the pre- epidemic, to be secondary cases or to have traveled to Morocco. Compared to the pre-epidemic period and the epidemic period, there was a higher percentage of sub- jects who received a single dose of anti-hepatitis A vaccine (p=0.001). Taking into account only secondary cases repor- ted in the third period, the percentage of cases with incom- plete vaccination rises to 31%; in this group, a single dose of the vaccine was administered at a median of 11.5 days before the onset of symptoms. CONCLUSIONS: vaccination is of paramount importance for the prevention of hepatitis A in all risk groups, includ- ing adult males exposed to same-sex sexual intercourse and travelers to areas at high-medium endemic level, especially children, as the timeliness in the vaccination of contacts is fundamental and crucial for interrupting the chains of infec- tion. The observed increase in secondary cases and the delay in the administration of doses lead to a reflection on the need for greater promotion of vaccination, but also high- light the critical issues in the organization of vaccination ser- vices, mainly in the areas that have reported the greatest number of cases.

Background: Health care workers (HCWs) are at high risk of contracting an infection by SARS CoV-2 and thus they are a priority for vaccination. We hereby aim to investigate whether the risk of severe and moderate systemic symptoms (MSS) after vaccination is higher in HCWs with a history of previous COVID-19. Methods: An online questionnaire was offered to the cohort all HCWs undergoing anti-SARS CoV-2 mRNA BNT162b2 vaccination between January 4th and February 9th 2021 in two large tertiary hospitals (ASST Santi Paolo and Carlo) in Milan, Italy. Previous SARS-CoV-2 infection/COVID-19 was recorded. Local and systemic symptoms after each of the two doses were reported. MSS were those either interfering with daily activities or resulting in time off-work. Factors associated to MSS were identified by logistic regression. Findings: 3,078 HCW were included. Previous SARS-CoV-2 infection/COVID-19 occurred in 396 subjects (12.9%). 59.6% suffered from >= 1 local or systemic symptom after the first and 73.4% after the second dose. MSS occurred in 6.3% of cases (14.4% with previous vs 5.1% with no COVID-19 p <0.001) and in 28.3% (24.5% in COVID-19 vs 28.3% no COVID, p = 0.074) after the first and second dose, respectively. Subjects already experiencing COVID-19 had an independent 3-fold higher risk of MSS after the first and a 30% lower risk after the second dose. No severe adverse events were reported. Interpretation: Our data confirm in a real-world setting, the lack of severe adverse events and the short duration of reactogenicity in already infected HCWs. Possible differences in immune reactivity are drivers of MSS among this group of HCWs, as well as among females and younger individuals. (C) 2021 The Authors. Published by Elsevier Ltd.

Introduction: The coronavirus disease 2019 (COVID-19) epidemic is an infectious disease which was declared a pandemic and hit countries worldwide from the beginning of the year 2020. Despite the emergency vigilance plans, health systems in all countries experienced a different ratio of lethality, amount of admissions to intensive care units and quarantine management of positive patients. The aim of this study is to investigate whether some epidemiological estimates could have been useful in understanding the capacity of the Italian Regional Health Services to manage the COVID-19 epidemic. Methods: We have compared data between two different Italian regions in the Northern part of Italy (Lombardy and Veneto) and the national data to determine whether different health strategies might be significant in explaining dissimilar patterns of the COVID-19 epidemic in Italy. Data have been extracted from a public database and were available only in an aggregated form. Results: The regions in question displayed two different health policies to face the COVID-19 epidemic: while Veneto's health service was largely territorially oriented, Lombardy's strategy was more hospital-centered. Discussion: The key to facing epidemics like this one consists in identifying solutions outside of hospitals. This however requires there be well-trained general practitioners and enough healthcare personnel working outside hospitals.

BACKGROUND:hepatitis E is a disease spread all over the world, with endemic levels varying according to ecological and socioeconomic factors. In developing countries, large epidemics spread mainly through contaminated water; in developed countries, hepatitis E has always been considered a sporadic disease, closely associated to the travels to endemic areas, especially in Southeastern Asia. In the last years, this perception is significantly changing, because of an increasing number of autochthonous cases reported in many European countries.OBJECTIVES:to describe the epidemiological picture of hepatitis E in Italy from 2007 to 2019.DESIGN:descriptive study based on the cases reported to the special surveillance of acute viral hepatitis (SEIEVA); case-control analytical study for the analysis of risk factors associated with hepatitis E.SETTING AND PARTICIPANTS:hepatitis E cases reported to SEIEVA in the period 2007-2019.MAIN OUTCOME MEASURES:number of cases notified by year, percentages of cases exposed to known risk factors, odds ratios.RESULTS:from January 2007 to June 2019, 385 hepatitis E cases were notified to SEIEVA. The annual number increased from 12 in 2007 to 49 in 2018, the increasing trend continued in 2019, when 39 cases were observed in the first 6 months of the year. Northern and Central Regions reported most of the cases; only a few were diagnosed in Southern Regions. Based on SEIEVA data, the trend of hepatitis E notifications has increased according to the increasing propensity to the differentiated diagnosis, at least until 2018. However, only 46% of suspected cases are tested to detect the presence of anti-HEV IgM antibodies, during the observation period; the percentage of tested cases is significantly lower in the South than in Northern and Central Italy (p<0.001). The reported cases have a median age of 48 years (range: 5-87) and are mostly males (80%); 32% was observed in foreign citizens mainly from endemic areas of South Asia (Bangladesh, India, and Pakistan). In 72.5% of cases, the infection was contracted in Italy. The most frequent risk factor is the consumption of raw or undercooked pork meat, especially sausages (70% of cases), significantly associated with hepatitis E risk (OR 3.0; IC95% 1.4-6.1). Other important risk factors are wild boar sausages consumption (40% of cases, OR 4.6, not statistically significant), and travels to endemic areas during the six weeks before the disease (31% of cases, OR 3.2; IC95% 1.6-6.4).CONCLUSIONS:hepatitis E can now be considered as endemic even in industrialized countries. In Italy, from 2007 an increasing number of cases has been reported. However, the real impact of HEV infection is still underestimated due to the limited number of clinical centres which perform tests for the search of anti-HEV IgM antibodies in cases of acute hepatitis. An ad hoc surveillance has been activated in January 2019 in some Local Health Units/Regions and extended to a national level starting from January 2020. This initiative is necessary in order to better dimension the burden of the disease associated with HEV infection, to study its epidemiology, and to increase awareness of this infection among health professionals.