Persistent chemosensory dysfunction in COVID-19 patients: a deep dive into the psychophysical and genetic characterisation of an Italian cohort

Background/Objectives: Chemosensory dysfunction is a hallmark of SARS-CoV-2 infection;nevertheless, the genetic factors predisposing to long-term smell and taste loss are still unknown. This study aims to identify candidate genes possibly involved in persistent smell/taste loss through Whole Genome Sequencing (WGS) analysis of a large cohort of 130 fully characterised Italian individuals, previously diagnosed with COVID-19. Method(s): DNA of all analysed patients was used to perform WGS analysis, and a detailed personal anamnesis was collected. Moreover, orthonasal function was assessed through the extended Sniffin' Sticks test, retronasal function was tested with 20 powdered tasteless aromas, and taste was determined with validated Taste Strips. Self-reported smell and taste alterations were assessed via Visual Analog Scales plus questionnaires. Result(s): The clinical evaluation allowed to classify the patients in two groups: 88 cases affected by persistent smell dysfunction (median age, 49) and 42 controls (median age, 51). Among cases, 26.1% (n = 23) were functionally anosmic and 73.9% (n = 65) were hyposmic. Within cases, 77 underwent the taste strip test: 53.2% (n = 41) presented hypogeusia and 46.8% (n = 36) were normogeusic. Preliminary WGS results on a first subset of 76 samples confirmed the important role of UGT2A1 gene, previously described as involved in smell loss. Interestingly, we identified a nonsense variant (rs111696697, MAF 0.046) significantly associated with anosmia in males (p-value: 0.0183). Conclusion(s): Here, for the first time a large cohort of patients, fully characterised through a comprehensive psychophysical evaluation of smell and taste, have been analysed to better define the genetic bases of COVID-19-related persistent chemosensory dysfunction.

Italian ancestral HLA haplotype predisposing to severe COVID-19 by low spike and high IFNalpha binding affinity

Background/Objectives: Validated association between COVID-19 and the most obvious candidate genes, e.g. HLA, is still missing. A weak association with class I HLA-C*04:01 was found for infection in Sardinians and for severity in another mixed population. Auto-antibodies to interferon type I have been implicated in the severity of COVID-19 in two studies. Method(s): The binding affinity between HLA molecules and SARS-CoV-2 spike protein and IFNalpha subunits was evaluated in silico. The presence of antibodies against one or more of the 12 IFNalpha subunits was evaluated in 160 hospitalized COVID-19 patients. The 10 most frequent haplotypes in the Italian population were tested in 1.997 SARS-CoV-2 infected patients (hospitalized versus not hospitalized). Result(s): The presence of auto-antibodies against at least one IFNalpha subunit was detected in 26% of patients. The haplotype A*24:02-B*35:02-C*04:01-DRB1*11:04-DQB1*03:01 was found to predispose to severity (p = 0.0018;p = 0.07 after Bonferroni correction) in patients <50 years. The haplotype includes alleles able to bind spike with low affinity (i.e. C*04:01 and DRB1*11:04) and IFNalpha with high affinity (i.e. DRB1*11:04). Conclusion(s): One of the 10 most frequent ancestral haplotype of the Italian population predisposes to severity likely reducing both innate immunity through IFNalpha auto-antibodies induction and adaptive immunity through weaker spike protein presentation.

Identification of genetic determinants of COVID-19 severity by exome sequencing

Background/Objectives: The severity of the symptoms of coronavirus disease 2019 (COVID-19) has been associated to age, comorbidity, and male sex. Besides virus characteristics, host genetic factors influence the infection outcome. Different genome-wide association studies and meta-analyses investigated the contribution of common variants, whereas the role of rare variants just started to be elucidated. Our goal is to determine the contribution of rare variants to the development of severe COVID-19 in the Italian population. Method(s): We compared the genetic background of 215 severe COVID-19 patients with 1764 individuals from the general population. Rare variants (minor allele frequency <1%) from wholeexome sequencing data were retrieved using a bioinformatics variant discovery pipeline. We tested the impact of rare variants (classified according to their predicted effect on the gene product) both using a burden test design, and an iterative machine learning (ML) approach. Result(s): We identified a total of 690,000 rare variants in the entire examined population. Among them, 250 were associated with COVID-19 severity at a nominal P < 0.05. Gene-based burden test revealed a gene with an excess of loss-of-function mutations at P < 0.05. Finally, the ML approach, analysing all the 690,000 rare variants, identified the best combination of variants that is able to predict COVID-19 severity in our cohort. Conclusion(s): Our work provides new insights on the genetic signature of COVID-19 in the Italian population. The most informative rare variants could be exploited to define individuals' risk profiles to COVID-19 severity for the Italian population.

Aggressive behavior in Italian children with ADHD in the middle of COVID-19 pandemic: Preliminary data on MAOA gene polymorphisms involvement

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by oppositional, defiant, disobedient, disruptive and also aggressive behavior. Many genes are involved in its onset, particularly dopaminergic pathway genes. Moreover, genetic predisposition to aggression appears affected by the polymorphic genetic variants of the serotoninergic system, among which, functional polymorphisms in monoamine oxidase A (MAOA). The risk of contracting coronavirus infection may arouse in some people severe emotional distress characterized by symptoms of fatigue, guilt, and aggression. A survey on the psychological impact of COVID-19 pandemic in Italian families of children with neurodevelopmental disorders such as ADHD showed how children have been particularly affected by the emergency. The aim of this study was to determine whether polymorphisms at the MAOA gene are associated with increased or reduced susceptibility to develop ADHD. Therefore, the variants rs6323, rs587777457 and rs1137070 of the MAOA gene were evaluated by SBT in 35 children (mean age 10.257 range 6-16) with ADHD and 27 healthy individuals. Our analysis allowed us to identify the G/G genotype of the variant rs6323 (Arg297Arg) was significantly associated with an increased risk of ADHD (p = 0.015). Allele G indicates higher levels of the enzyme, while the T allele indicates lower levels of enzyme production. When compared in patients, the G allele was associated with higher anger (p-value = 0.01) and might cause aggressive behavior in males. Our study shows that defining a genetic profile of ADHD can provide important information on the etiopathogenesis of the disease and help identify the best therapeutic option for patients with this disorder.

Postmarketing data collection and evidence evaluation

AIFA Monitoring Registries (wMRs) constitute a collection of drug registries (product registries) deployed to physicians and pharmacists through a national web platform. They have been adopted in the clinical practice since 2005 and are used to define the population for which the drug is available under the umbrella of the National Health Service (NHS - Servizio Sanitario Nazionale SSN), monitor prescription appropriateness and ensure the rapid access to potentially priority medicines allowing the implementation of patient-based managed entry agreements (MEAs). Each registry consists of specific data entry forms, collecting data at the patient level and filled in by authorized clinicians and pharmacists. The required information includes: 1. Registration form with patient personal data (anonymized after registration);2. Eligibility and clinical data form;3. Prescription and administration forms;4. Evaluation of disease status and treatment update form;and 5. End-of-treatment form. Evaluation and end-of-treatment forms provide main safety and effectiveness data at a patient level. Moreover, since entry forms are the same throughout the nation, this platform allows access to treatment in a homogeneous manner throughout the country. Recently, a new type of registry has been released, with the primary aim of monitoring the pregnancy prevention programme (PPP) following the prescription of potentially teratogenic medicinal products. All this information is collected in a national database that represents a key source of postmarketing evidence that is frequently exploited to answer both administrative and clinical questions, such as drug utilization among a specific pharmacological class or the effectiveness of a drug in a census consisting of all Italian patients treated with that medicinal product. For example, given the prospective nature of the data contained inside the wMRs, AIFA together with members of the relevant scientific associations were able to evaluate the effect of the COVID- 19 pandemic and lockdown measures on the new prescription (i.e. first prescription) of some cardiovascular drugs in Italy and suggest new studies to analyse the occurrence of new cardiovascular- related events resulting from the decline in the activation of these treatments. Equally important is the work assessing the effectiveness of tyrosine kinase inhibitors in chronic myeloid leukaemia (CML) patients in Italian clinical practice, which was able to highlight important aspects on both expected mortality and consequential use in first and second line TKIs in Italy. Finally, the wMRs were also a critical instrument in the management of the COVID-19 medicinal products since 29 October 2020, providing essential evidence on drug availability through the country, predicting possible shortages and publishing hundreds of freely available reports on the utilization trend of COVID-19 drugs in the different Italian Regions. In conclusion, the wMRs represent a key tool to generate pharmaco-epidemiological evidences in the Real-world setting and monitoring drug appropriateness for expensive, innovative drug.

Preventing Psychopathology in Different Stages of Development: Comparing Experiences

Preventing psychopathology and promoting well-being have always been objecting of concern in many fields of psychology and psychiatry. Prevention is a form of intervention aimed at preventing the onset of a symptom, disorder, and psychological and/or social distress. The symposium intends to compare prevention in various contexts and different developmental stages of life, through the presentation of 4 contributions: (a) "Coping strategies and mental health during the covid-19 pandemic: an Italian survey". The study aims to evaluate mental health starting from individual characteristics and to explore which coping strategies are effective in enhancing the Italian population's well-being in dealing with covid-19;(b) "The role of several aspects of personality in the construction of transversal competencies in a sample of young adults". The study aims to assess the role that self-criticism, dependency and efficacy play in enhancing the young adult's transversal skills to facilitate more adaptive and satisfying life trajectories;(c) "Mentalization and attachment representation in mother-child and teacher-student relationships". The study has two aims: the first is to evaluate the relationship between the mentalization abilities and the attachment representation of both mother and her child and the teacher and her/his pupils. The second is to verify whether the adult's (mother and teacher) mentalization abilities impact the child's mentalization abilities;(d) 'Psychopathological symptoms and mentalizing capabilities in adolescents with anorexia nervosa before and during COVID-19 pandemic. This study aims to compare Covid-Period vs. NON-Covid Period adolescent patients affected by Anorexia Nervosa (AN) considering their psychopathological symptoms and their mentalizing capabilities. In the symposium, three types of prevention are focused: primary, secondary, and tertiary. The primary aim is to avoid or minimise the risk of occurrence. Secondary prevention intervenes early on the problem to reduce its negative effects. A clear example is an early diagnosis, which is even more important when dealing with childhood disorders as it increases treatment opportunities, effectiveness, and positive outcomes. Tertiary prevention relates to preventing complications and reducing the risk of relapse. The symposium's objective is to compare various typologies of prevention in different contexts focusing on specific samples. The four contributions illustrate once again the greatest importance of prevention and how it can be broadly applied, in clinical, social, and developmental contexts.

Coping Strategies and Mental Health during the Covid-19 Pandemic: An Italian Survey

Introduction: The COVID-19 pandemic is still having a strong impact on psychological and mental health worldwide. The pandemic generated a change in people's life and fear, loss of structure of daily routine, physical illness, depression, and stress, are only some of the potentially long-term consequences. The coping strategies used to deal with these difficulties may have influenced the perception of well-being, so the present study aimed to evaluate mental health in relation to individual characteristics and to explore the more effective coping strategies used by the Italian population and their impact on psychological well-being. Method(s): The web-based survey was delivered by Qualtrics between 30 November and 10 December 2020. A total of 537 individuals (>18) were recruited and all participants completed measures of sociodemographic data, general psychological well-being (PGWBI), and coping strategies (COPE-NVI). Result(s): Females, students, and unmarried people reported the lowest levels of mental health. Specifically, the coping strategy called "positive attitude" was positively correlated with psychological well-being, while "avoidance" and "social support strategies" negatively influenced it. The coping strategies named "problem-focused" and "transcendentoriented" resulted not statistically significant. Conclusion(s): The use of maladaptive strategies (e.g., avoidance-oriented) set up negative symptoms such as anxiety or depression whereas the beneficial ones can be central to optimally managing the psychological effects of long-lasting current COVID-19. From a preventive point of view, it is hence important to take care both of those who are already suffering from psychological disorders and of the non-clinical population, starting to question how psychopathology will change after the pandemic. New treatment directions should be found. The results suggest that to prevent mental disorders, therapists must consider the use of coping strategies in clinical practice. Implications for clinical preventive interventions are reported.

Personality, Defenses, Mentalization, and Epistemic Trust Related to Covid-19 Containment Strategies: A Psychodynamic Perspective

Introduction: The COVID-19 pandemic has considerably influenced all the domains of people's lives worldwide, determining a high increase in overall psychological distress and several clinical conditions. The study attempted to shed light on the relationship between strategies adopted to manage the pandemic, vaccine hesitancy, and distinct features of personality and mental functioning. Method(s): The sample consisted of 367 Italian individuals (68.1% women, 31.9% men;M age=37, SD=12.79) who completed an online survey including an instrument assessing four response styles to the pandemic and lockdown(s) (RSPL;Tanzilli et al., 2021), the Personality Inventory for DSM-5-Brief Form (PID-BF;Krueger et al., 2013), the Defense Mechanisms Rating Scales-Self-Report-30 (DMRS-SR-30;Di Giuseppe et al., 2020, 2014), the Reflective Functioning Questionnaire (RFQ;Fonagy et al., 2016), and the Epistemic Trust, Mistrust, Credulity Questionnaire (ETMCQ;Campbell et al., 2021). Result(s): Maladaptive response patterns to pandemic restrictions were related to dysfunctional personality traits, immature defense mechanisms, poor mentalization, and epistemic mistrust or credulity. Moreover, more severe levels of personality pathology was predictive of an extraverted-maladaptive response style to health emergency through the full mediation of low overall defensive functioning, poor certainty of others' mental states, and high epistemic credulity. Conclusion(s): Recognizing and understanding dysfunctional psychological pathways associated with individuals' difficulties in dealing with the pandemic are crucial for developing tailored mental health interventions and promoting best practices in healthcare services.

Vaccination coverage during pregnancy and factors associated with refusal

Objective. The vaccines currently recommended during pregnancy are the dTpa, the influenza vaccine, and, due to SARSCoV- 2 pandemic, the mRNA vaccine against COVID-19. The aim of this study was to evaluate vaccination coverage among pregnant women and factors associated with refusal. Materials and Methods. 307 patients who delivered at term between March and April 2022 at Careggi Hospital answered a questionnaire about vaccines during pregnancy. The primary aim was to assess vaccination coverage and factors associated with refusal. The secondary aim was to detect differences in vaccination between Italian and foreign women. Results. Overall, 74% of patients were vaccinated with dTpa, 82% against COVID-19 and only 33% against Influenza. Vaccination coverage for dTpa and COVID-19 was significantly higher among Italian than foreign patients (80% vs 51%, p < 0.001 and 86% vs 69%, p = 0.002, respectively). 89% of patients received recommendations for vaccines from the gynecologist, more frequently among Italians than foreigners (p = 0.01). The main reasons behind refusal of vaccinations were: reduced perception of the risk of disease in the case of influenza (41%), inadequate information received from the gynecologist regarding dTpa (35%), fear of side effects (63%) and of effects on the fetus (70%) from the COVID-19 vaccine. Conclusions. Adherence to the Influenza vaccine was low because of reduced perception of the disease risks. Fear of COVID-19 disease led most of the patients to receive the vaccination. The significant difference in vaccination coverage between Italians and foreigners is likely due to less information being received by foreign patients, an example of health care disparity.

Prevalence and Persistence of Hypovitaminosis D among Italian Patients with Myocardial Infarction

Background: Hypovitaminosis D is common in the Italian population and has a comparable effect to diabetes mellitus on survival after an acute myocardial infarction (AMI). We aimed to evaluate if the prevalence of hypovitaminosis D changed over time, considering also frequent lockdowns in the last years due to COVID-19 pandemic. Method(s): According to the year of enrollment, we divided our cohort of 1042 patients hospitalized for AMI, into three groups (group 1 with 368 patients enrolled from 2014 till 2016, group 2 with 470 patients enrolled in the period from 2017 till 2019, and group 3 including 204 patients enrolled in the last three years, from 2020 till 2022) and evaluate whether the concentration of vitamin D changed in the last decade. Result(s): The median concentration of vitamin D in our cohort of patients with AMI was 18.2 (11.48-25.73) ng/ml). Throughout the three groups (2014-2016, 2017-2019, 2020-2022), the median plasma vitamin D showed a trend toward an increase (17.3 (10.33-24.2) ng/ml, 18.95 (11.6-26.73) ng/ml, and 19.05 (12.5-27.3) ng/ml respectively), which was significant between the group 1 vs 2 and 3 (p = 0.033 and p = 0.004, respectively), while between the group 2 and 3 did not. Despite the trend of increase, the percentage of patients with hypovitaminosis D in each group remained high (61.4%, 53.8% and 52.0% respectively). As expected, samples taken between May and September have significantly higher vitamin D values compared to ones taken from October to April for each group (the group 1: 21.80 (15.55-31.23) ng/ml vs 15.8 (9.22-23.98) ng/ml, p < 0.0001;the group 2: 22.05 (14.10-30.98) ng/ml vs 16.50 (11.03-23.90) ng/ml, p < 0.0001);the group 3: 20.00 (11.90-26.90) ng/ml vs 16.30 (9.75-22.30) ng/ml, p = 0.001). Conclusion(s): There has been a trend of increasing vitamin D values over the years, but hypovitaminosis D remains frequent. During the pandemic, vitamin D levels did not decrease due to frequent lockdowns, possibly due to media awareness that emphasized the significance of vitamin D administration against viral infection.

Boredom, loneliness and modern type depression in a cohort of Italian university students

Introduction: COVID-19-related physical isolation, fear and anxiety determined de novo mental illnesses, by potentially facilitating the emergence of Hikikomori traits (i.e., a severe social withdrawal condition). Objective(s): The present study aims at screening a cohort of university students for the Hikikomori traits and assessing a set of psychopathological determinants associated with Hikikomori, particularly boredom and loneliness dimensions. Method(s): A cross-sectional web-based survey was carried out by administering Hikikomori Questionnaire (HQ-11), Italian Loneliness Scale (ILS), Multidimensional State Boredom Scale (MSBS), Depression Anxiety Stress Scale (DASS-21) and Toronto Alexithymia Scale (TAS-20). Result(s): 1,148 respondents (767 women and 374 men, mean age: 23.2+/-SD=2.8 years old) were recruited. 70.7% declared to have experienced psychological distress. HQ-11 average total score was 18.4+/-SD=7.5 with statistically significant higher values in the males (p=0.017) and amongst students studying Informatics, Mathematics/Physics/Chemistry, Science of Communication and Engineering. The HQ-11 positively correlated with ILS (r=0.609), MSBS (r=0.415), TAS-20 (r=0.482) and DASS-21 (r=0.434). Conclusion(s): This study represents the first screening of the Hikikomori phenomenon in Italian university students. Hikikomori traits appear to be particularly represented in the Italian youth population and should be carefully investigated in future studies.

Therapeutic adherence and quality of care of MS patients during COVID-19 pandemic: an italian multicenter patient-centered survey (COVIMPSAT)

Introduction and aims: Multiple Sclerosis (MS) Centers experienced a significant disruption of their clinical activities during the first waves of COVID-19 pandemic. As part of a national multicenter survey (COVId Ms Patients SATisfaction survey - COVIMPSAT), we collected i) the opinion on quality of care (QoC) received by people with MS (pwMS) from MS Centers (MSC), and ii) data on therapeutic adherence and discontinuation, during the lockdown period (March-May 2020) in Italy. Method(s): In April-May 2021, 16 Italian MSC compiled and sent a digital (35-item) survey to their patients. Statistical analyses were performed with SPSS, version 25. Result(s): 1670 pwMS (67.3% women) completed the survey. Most of them (89.9%) were on disease-modifying therapies (DMTs). The most used DMTs were dimethyl fumarate (18.6%), ocrelizumab (14.4%) and natalizumab (13.9%). During the lockdown period, 88% did not modify their DMT regimen, while 11% reported a change in DMT intake, with a reduction in 7.8% and a drug discontinuation in only 4.2% cases. Almost 9 out of 10 pwMS (89.1%) were able to get in contact with their MSC without difficulties. Thirty-six percent of pwMS contacted their MSC for getting information about COVID-19, while 30% were directly contacted from the MSC personnel to provide information on MS and COVID-19 and preventive behaviours. More than half of the patients (63.5%) performed their check-up visits at the MSC with the same schedule as the pre-pandemic period, while 36.5% of pwMS voluntary skipped follow-up visits mainly because of fear of getting COVID-19 infection (46%) and the sensation of feeling well without an absolute/urgent need of a check-up visit (16.8%). Interestingly, although only 1.3% of pwMS underwent a teleneurology follow-up visit, 80% of patients suggested to invest more in telemedicine programs in order to expand contact channels with MSC. The overall opinion of pwMS on MSC during the pandemic period in Italy was more than positive, with 32% of pwMS declaring a significant increase in trust in their MSC. Conclusion(s): Italian pwMS judged globally well the activity, accessibility and information received by their MSC during the first wave of COVID-19 pandemic. Only 1 out of 10 pwMS underwent a change in their DMT regimen, showing a high drug adherence. Our data also demonstrate that implementing telemedicine programs would further improve the QoC of patients, particularly those with higher disability or living far from the MSC.

Two years later: Reassuring longitudinal trajectories of sleep quality, insomnia, and mental health over the endless pandemic

Objectives/introduction: Since the first lockdown period of Spring 2020, the several COVID-19 contagion waves deeply impacted the sleep and mental health of the general population. Notwithstanding the largest vaccination campaign in human history, the pandemic has continued to disrupt the daily life of the worldwide population for two years now. Here, we report preliminary results on the longitudinal trajectories of sleep quality, insomnia, and mental health throughout the pandemic in Italy. Method(s): A total of 1039 Italians (mean age +/- standard error, 35.37 years +/- 0.39;18-81, 201 males) participated in a longitudinal study consisting of three survey waves. Subjects were evaluated during the first two contagion waves (T1: April 2020, T2: December 2020) and after two years from the first lockdown period (T3: April 2022). The survey comprised: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Beck Depression Inventory-second edition (BDI-II), and the state-anxiety subscale of the State-Trait Anxiety Inventory (STAIX1). Longitudinal data were analysed using linear mixed models. Result(s): Analysis showed unchanged PSQI overall score (p = 0.20;T1: 6.69 +/- 0.11;T2: 6.70 +/- 0.11;T3: 6.54 +/- 0.11). Comparisons on PSQI sub-components revealed improved subjective sleep quality, sleep latency, and sleep disturbances at T3 than at T1 (all p < 0.002). Conversely, participants reported shorter sleep duration and higher daytime dysfunctions at T3 than at T1 (both p < 0.001). Finally, the analyses highlighted differences in ISI (p < 0.001), BDI-II (p = 0.03), and STAI-X1 scores (p < 0.001) between the three assessment points. Bonferroni post hoc showed reduced ISI (T1: 8.05 +/- 0.16;T2: 7.42 +/- 0.16;T3: 6.96 +/- 0.16), and STAI-X1 scores (T1: 48.14 +/- 0.30;T2: 46.24 +/- 0.30;T3: 45.23 +/- 0.30) over time (all p < 0.01), and lower BDI-II scores (T1: 11.80 +/- 0.28;T2: 11.69 +/- 0.28;T3: 11.15 +/- 0.28) at T3 than at T1 (p = 0.03). Conclusion(s): Our study described a reassuring scenario after two years of the pandemic. We demonstrated relieving sleep disturbances, insomnia, depressive, and anxiety symptoms in a context of shorter sleep duration and more severe sleep-related daytime dysfunctions. Further long-term monitoring of sleep and mental health time course is necessary to claim the end of the pandemic emergency on sleep and psychological status of the general population.

Retrospective cohort study on weight gain among pregnant women of the Italian Province of Trento during the 2020 lockdown due to COVID-19

Objective. The lockdown due to COVID-19 has been associated with a reduction of physical activity and a change in eating behaviors, with consequent weight gain, in general and specific populations. The objective of this study was to assess whether women whose pregnancies encompassed the lockdown due to COVID-19 in 2020 had an excess gestational weight gain as compared with those who were pregnant in the same periods of previous years. Materials and Methods. This was a retrospective cohort study based on anony-mous data from the Birth Attendance Certificate (CedAP) information flow which is mandatorily collected in all Italian Regions. In the Autonomous Province of Trento, North-Eastern Italy, more information than those required as a minimum data set are collected, including maternal weight at the first gestational obstetric visit, initial body mass index (BMI), and maternal weight at delivery. We calculat-ed mean gestational weight gain for women whose pregnancy encompassed the 2-month lockdown in 2020 and for those who were pregnant in corresponding periods of the years 2016-2019. Linear and logistic regression models were built to assess the association between lockdown and weight gain or excess weight gain, respectively, adjusting for the potential confounding effect of gestational month at the beginning of lockdown or corresponding period and pre-pregnancy body mass index. Results. In 2020, mean gestational weight gain was not significantly different from the previous years, nor was the likelihood of gaining excess weight. Conclusions. Unlike other populations that increased weight during the COVID-19 lockdown, the Italian population of pregnant women described in this study has a gestational weight gain comparable with that of the previous years. Public health and environmental interventions, as well as dedicated programs taking care of women from conception to post-partum may have a role in the health of future mothers and should be promoted.

State boredom and behavioral addictions: Evidence of psychometric adequacy for the Short Form of the Multidimensional State Boredom Scale with young adults

The hypothesis that State boredom (SB) - the experience of boredom in the moment - can be considered as one of the risk factors for engaging in addictive behaviors has been further supported by the studies conducted during the COVID-19 related lockdown. Moreover, the issue of gender-related differences and similarities in SB is in debate. However, to deeply assess SB, it is fundamental having sound measurement instruments. One of the mostly used and brief instruments employed internationally to assess SB is the Short Form of the Multidimensional State Boredom Scale (MSBS-SF), but evidence regarding its psychometric properties among young adults, who are particularly at-risk for the development of behavioral addictions, is lacking. In particular, the functioning of the scale across genders is unknown in this age group. As a result, we used item response theory (IRT) to investigate psychometric functioning, with a specific focus on gender invariance, of the MSBS-SF among young adults. Eight hundred and twenty five Italian young adults (73% female;Mage = 25.61, SD = 4.53) were recruited. A confirmatory factor analysis demonstrated the unidimensionality of the scale, and IRT analyses indicated that the scale was sufficiently informative. Differential item functioning (DIF) across genders showed that items had an equivalent functioning across male and female respondents. Additionally, significant and positive relationships with hypersexual behavior were found. Overall, this study offers evidence that the MSBS-SF is a valuable and useful scale for measuring SB among male and female young adults.

Exercise addiction during the Covid-19 pandemic in Italy

Severe restrictive measures were implemented globally to limit the spread of the Covid-19 pandemic leading to significant lifestyle changes and impacting on both the physical and the mental health of citizens. Caught by the fear of getting sick, some individuals have adopted behaviors which favored the development of Exercise Addiction (EA). Our aim was to evaluate the incidence of EA in the general Italian population during Phase 1 of the lockdown, and the role of Appearance Anxiety (AA), self-compassion and use of Performance and Image Enhancing Drugs (PIEDs) as predictors of its development. Between April to May 2020 an online survey was conducted across Italy. The rate of EA in the full sample (953 subjects) was 3.6%. 84.2% of the participants reported variations in their fitness routine. Perceived benefit of exercising resulted significantly higher in those with EA. Subjects with EA reported stronger motivation in engaging in physical activity as for physical wellness, psychological wellbeing and sexual attractiveness and confidence in relationship. A higher level of AA, a lower level of self-compassion, the use of PIEDs and a higher perceived benefit of exercising during lockdown were all significant predictors for the presence of EA. Our findings suggest that the fear of getting sick from Covid-19, combined with radical changes in the lifestyles induced by the lockdown and individual personological characteristics can favor the development of AE and related phenomena in the general population.

AUTOIMMUNITY PROFILE and LUNG INVOLVEMENT in ITALIAN PATIENTS with DERMATOMYOSITIS during COVID-19 PANDEMIA

Background: Dermatomyositis (DM) is a rare idiopathic infammatory myopathy that can present with a variable spectrum of cutaneous and systemic manifes-tations1. Correlations between myositis-specifc autoantibodies (MSAs) and disease phenotype have been documented in DM in particular in association with the development of interstitial lung disease (ILD). Ongoing studies focus on the potential role of MSAs in similarities of the pathophysiological mechanisms of COVID-19 associated ILD and that related to DM suggesting an intriguing cross talk between autoimmunity and COVID-192. Objectives: To explore clinical patterns including ILD and MSAs profile in DM patients from a population-based single-center study carried out in a Tertiary Referral Rheumatologic Clinic. SARS-CoV-2 infections and vaccination were also analysed. Methods: We enrolled patients affected by DM classified according to 2017 EULAR/ACR criteria1 with a disease onset at ≥18 years referring to the Rheumatologic Clinic of Tor Vergata University Hospital in Rome (Italy). Clinical data were collected from medical records: gender, age of onset of symptoms and diagnosis, clinical features, auto-antibodies patterns (ANA, MSAs including anti-tRNA synthetase,-Jo1,-PL7,-EJ,-MDA5,-NXP2, SAE, Mi2, and myositis-associated antibodies comprising anti-PM/Scl,-Ro-52,-Ku, U1RNP), pattern of lung abnormalities at thoracic CT scans, and treatments. The prevalence of SARS-CoV-2 infection and vaccination profile were also investigated. Results: Among eligible cases (n=30), patients who completed the study (n=19) included almost entirely women (F=73.7%). The median age at disease onset was 57.4±12.4 yrs while the mean diagnostic delay resulted as 12±10 months. Skin manifestations and myalgia were the prevalent symptoms (79% and 63%, respectively) whereas dyspnea and cough occurred in a third of the cohort at DM onset. Besides the skin involvement, the decrease in pulmonary function was the main clinical manifestation at the frst rheumatological referral (52.6% of cases) followed by joint pain (36.8%) and cardiovascular events (10.6%). ANA titer≥1:160 occurred in 79% of patients. All patients showed MSAs positivity with a similar distribution: a single case of double positivity was registered in a man with anti-MDA5 and-NXP2. The most common CT fndings were ground-glass opacity and parenchymal band in a third of patients (32%). The entire cohort had undergone cycles of steroids from the onset of DM and during the follow-up, according to disease severity. The main used therapies were methotrexate (47%), intravenous immunoglobulin (42%) and mofetil micofenolate (31.6%). None of patients had SARS-CoV-2 infection (until December 2021). The 63% of the cohort received at least one dose of the anti-SARS-CoV-2 mRNA vaccine (BNT162b2), of which 10% had completed with the booster dose. No adverse reactions or post-vaccination DM fare were registered. A third of the cohort had not been vaccinated due to concomitant disease activity or therapies. No cases of post-COVID19 new-onset DM were diagnosed. Conclusion: Our preliminary findings support the relevant impact of lung involvement in DM. The availability of MSAs can help to stratify patients with DM for outcome and risk of potential disease complications. The impact of MSAs on ILD associated or not to COVID-19 deserve further investigations in a larger DM cohort and for a longer post-COVID-19 pandemia follow-up time.

THE USE of ORAL AMINO-BISPHOSPHONATES and CORONAVIRUS DISEASE 2019 (COVID-19) OUTCOMES

Background: The determinants of the susceptibility to SARS-CoV-2 infection and severe Coronavirus Disease 19 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-infammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events and cancer. Objectives: We conducted a population-based retrospective observational case control study with the primary objective of determining if oral N-BPs treatment can play a role in thesusceptibility to the development of severe COVID-19. Methods: Administrative ICD-9-CM and AT C data, representative of Italian population (9% sample of the overallpopulation), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis. Patients treated with bisphosphonates (cases) were randomly matched (1:1 ratio) for age, sex and for other clinically relevant variables (presence of treatments other than bisphosphonates and hospitalizations) with all the health-assisted population without this treatment (controls). Results: Incidence of Covid-19 hospitalization was 12.32 [95%CI 9.61-15.04] and 11.55 [95%CI 8.91-14.20], of ICU utilization due to COVID-19 was 1.25 [95%CI 0.38-2.11] and 1.42 [95%CI 0.49-2.36] and of all-cause death was4.06 [95%CI 2.50-5.61] and 3.96 [95%CI 2.41-5.51] for oral N-BPs users and non-users, respectively (Figure 1A). Figure 1B Incidence and 95% CI of COVID-19 related events in N-BPs treated and untreated subjects with anti-osteoporotic drugs and without corticos-teroids. C. Incidence and 95% CI of COVID-19 related events in N-BPs treated and untreated without previous vertebral or hip fragility fractures. D. Incidence of COVID-19related events in bisphosphonates treated and untreated patients without previous vertebral or hip fracture without corticosteroid prescriptions. Conclusion: In conclusion, we found that the incidence of COVID-19 hospi-talization, intensive care unit (ICU) utilization and COVID-19 potentially related mortality were similar in N-BPs treated and non-treated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provided real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results strongly support national and international guidelines that advocate against the discontinuation of oral bisphosphonates only for the fear of COVID-19.

EXPLORING the IMPACT of the PANDEMIC on ITALIAN RHEUMATIC DISEASE PATIENTS: A PATIENT ADVOCACY SURVEY

Background: Patients with rheumatic diseases show impaired quality of life (QoL): disease activity, comorbidities and treatment-related side effects contributes to decrease physical, emotional, and social functioning. The COVID-19 pandemic challenged health care systems and patients with chronic conditions: hospital and outpatient clinics delayed access, unpredictable changes like non-adherence to medication, but also negative emotions, psychological conditions recognized as risk factors for the poor QoL [1-2]. Objectives: To describe the impact of the COVID-19 pandemic on the Qol of Italian patients with rheumatic diseases in the frst period of the national lockdown. Methods: APMARR (Associazione Nazionale Persone con Malattie Reu-matolgoche e Rare) invited Italian patients and caregivers to participate to an online structured survey in the period March-June 2020. Informed consent was retrieved. The questionnaire, promoted by the patient advocacy website, collected demographics, emotional and healthcare pattern information. Results: 87,44% (N=215) complete questionnaires were retrieved (96.3% patients;3.7% caregivers;87.77% female;2% aged <18 years, 16% aged 18-30 years, 82% aged >31 years;0.53% missing data). Respondents were illustrative of the Patient Advocacy regional distribution (Puglia Region predominant). Rheumatoid arthritis regarded 29% of respondents, ankylosing spondylitis 17%, psoriasis 16%, remaining 38% other rheumatoid diseases. 96% of respondents were employed, 39% of which had to discontinue/change working activity during pandemics. 60% of respondents reported being worried about their disease. The deriving sense of fragility was the main cause of anxiety, which was not controlled even by compliance to the treatment plan (88%). 30% of respondents was worried about virus infection. Irritability, appetite and sleep disorders were also reported: anxiety had effects on irritability (46% sometimes more irritable) and sleep quality (38% always disturbed). GPs visits access was limited (40% considered it absent and 76% had to postpone it). Only 32% of specialist centers provided facilitated patterns of care. Respondents suggested possible solutions to improve QoL during COVID-19 pandemic and over it. Psychologist support was suggested as useful by 44% of respondents to manage therapies and by 56% to effort daily life. The home infusion would be of support according to 44% of respondents (18% already got access to it). Patient Advocacy had a main role in the new care and life context: 80% would consider it useful to participate to and 81% was satisfed by the prompt and continuous support received during pandemics. Conclusion: Similar results as far as distress were reported by Italian and foreign evidence, which demonstrated considerable COVID-19 related psychosocial burden in rheumatic disease patients [3-5]. Potential solutions are also with EULAR recent guidelines, which underlined how psychological interventions were found to reduce pain and fatigue even in difficult-to-treat patients [6] and how mental health needs should be periodically assessed, due to the link between better emotional well-being and better self-management [7]. Besides, the reported picture of reorganised care during pandemic corresponded to the real-world experience of the Italian Regions [8]. New approaches of care like home infusions and telemedicine supported by patient organisations should become routinary and may therefore beneft patients.

RELAPSES of IDIOPATHIC INFLAMMATORY MYOPATHIES after VACCINATION AGAINST COVID19: A REAL-LIFE ITALIAN STUDY

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination plays a crucial role as pivotal strategies to curb the coronavirus dis-ease-19 (COVID-19) pandemic. Despite the mass-scale vaccination, literature data about the incidence of disease fares in IIM patients are still not reported as well as the immunological condition. Objectives: The present study aimed to describe the clinical status of patients affected by IIM after vaccination against COVID19 in order to assess the number of relapses or immune-mediated reactions in a cohort of Italian patients with such disease. Methods: We included all patients affected by IIM and followed by Myositis Clinic, Rheumatology and Respiratory Diseases Units, Siena University Hospital, Bari University Hospital, Policlinico Umberto I, Sapienza University, Rome, and Policlinico Paolo Giaccone, Palermo. Inclusion criteria were a recent (<3 months) clinical and serological assessment before the survey and a defnite diagnosis of dermatomyosi-tis, polymyositis and anti-synthetase syndrome. All patients underwent a telephone survey in order to establish their clinical status and potential relapses after vaccination. Results: A total of 119 IIM patients (median, IQR 58 (47-66) years;32 males) were consecutively enrolled. Fifty had a diagnosis of DM, 39 had PM and 30 had ASS. The median months of disease duration was 79.62±83.98. According to number of organs involvement, forty-two had only one, 45 had two organs involvement, 20 had three, 11 had four and one had five. The majority of them received two doses of COVID-19 vaccine, except four patients who refused the vaccination: 94 (78.9%) Cominarty, 16 (13.4%) Moderna, 5 (0.04%) AZ. Seven (0.06%) patients had fare after vaccination, the majority of them were mild except one major with three organs involved and one life-threatening with systemic involvement. In order to understand or predict the effect of demographic and clinical features on the fare development after vaccination, a logistic regression analysis was performed. The goodness-of-ft statistics showed a Chi2 associated with the Log ratio (L.R.) of 0.045. From the probability associated with the Chi-square tests, the Type II analysis showed the variable that most influences the development of fare was the number of organs involved (p=0.047). Sixty-eight patients received the third dose of COVID-19 vaccination: 51 (75%) Cominarty and 17 (25%) Moderna. Only one (0.01%) patient (the same who had life-threatening fare with systemic involvement after two doses) had fare after third dose and eventually died. Conclusion: Vaccines against SARS-CoV2 have provided, both in registratory studies and in preliminary real-life evidence, an overall good efficacy and safety. Nevertheless, only scanty data are available for rheumatic patients in general and the ones affected by IIM in particular. To the best of our knowledge, ours represent the largest cohort of IIM patients in which immunogenicity of anti-SARS-CoV2 vaccine was assessed. In line with real-life data from other diseases, we found a non-statistically signifcant risk of relapse in our patients, which occurred seldom, usually mild and in patients with a more severe and aggressive course of disease.