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Background: The acquisition of health information via the internet has emerged as a prevalent approach within the general population and is likely to exert an influence on health decision-making processes. This study aims to evaluate the comprehensive quality of online information about anxiety treatment and management comparing websites in English, which is widely used for international scientific communication, and Italian, a popular local language. It was used a multidimensional methodology that assesses scientific quality of information; readability of the website; the technological quality of the website and the website's popularity ranking., Methods: We conducted a systematic search on four widely used online search engines. Duplicated, unrelated websites, and scientific papers were excluded. The assessment included the use of several criteria and tools: the DISCERN scale, the JAMA benchmark criteria, adherence to the Health on the Net Code; the Nibbler tool; PageRank; and the Flesch Reading Ease test/the Gulpease readability index., Results: 78 websites in Italian and 60 in English were evaluated. Quality of information of the English websites was higher than that of the Italian ones, but only a small percentage of them reported high level information about all treatment types and shared decision-making process. Technological quality was higher in English websites. In general, all websites were difficult to read, requiring reading skills at the high school level or higher., Conclusions: These results can promote future guidelines to improve online health information. Users should be able to find information about all treatment types (pharmacological and psychosocial) in line with the current guidelines for the treatment and the management of anxiety disorders. This would help internet users to achieve a higher level of quality information., Competing Interests: Declaration of competing interest All the authors Paola Melis, Alessandra Perra, Antonio Egidio Nardi, Thurayya Zreik, Antonio Preti, Mauro Giovanni Carta declare: - There are no any relevant conflict of interest at any time and during the 36 months prior to publication; - There are no any patents, wether palenned, pending or issued, broadly, relevant to the work; - There are no other relationships/conditions/circumstances that present a potential conflict of interest; - In general the authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Long-term deterioration in the mental health of healthcare workers (HCWs) has been reported during and after the COVID-19 pandemic. Determining the impact of COVID-19 incidence and mortality rates on the mental health of HCWs is essential to prepare for potential new pandemics. This study aimed to investigate the association of COVID-19 incidence and mortality rates with depressive symptoms over 2 years among HCWs in 20 countries during and after the COVID-19 pandemic., Methods: This was a multi-country serial cross-sectional study using data from the first and second survey waves of the COVID-19 HEalth caRe wOrkErS (HEROES) global study. The HEROES study prospectively collected data from HCWs at various health facilities. The target population included HCWs with both clinical and non-clinical roles. In most countries, healthcare centers were recruited based on convenience sampling. As an independent variable, daily COVID-19 incidence and mortality rates were calculated using confirmed cases and deaths reported by Johns Hopkins University. These rates represent the average for the 7 days preceding the participants' response date. The primary outcome was depressive symptoms, assessed by the Patient Health Questionnaire-9. A multilevel linear mixed model (LMM) was conducted to investigate the association of depressive symptoms with the average incidence and mortality rates., Results: A total of 32,223 responses from the participants who responded to all measures used in this study on either the first or second survey, and on both the first and second surveys in 20 countries were included in the analysis. The mean age was 40.1 (SD = 11.1), and 23,619 responses (73.3%) were from females. The 9323 responses (28.9%) were nurses and 9119 (28.3%) were physicians. LMM showed that the incidence rate was significantly and positively associated with depressive symptoms (coefficient = 0.008, standard error 0.003, p = 0.003). The mortality rate was significantly and positively associated with depressive symptoms (coefficient = 0.049, se = 0.020, p = 0.017)., Conclusions: This is the first study to show an association between COVID-19 incidence and mortality rates with depressive symptoms among HCWs during the first 2 years of the outbreak in multiple countries. This study's findings indicate that additional mental health support for HCWs was needed when the COVID-19 incidence and mortality rates increase during and after the early phase of the pandemic, and these findings may apply to future pandemics., Trial Registration: Clinicaltrials.gov, NCT04352634., (© 2024. The Author(s).)

Background: It is difficult to quantify the impact of the COVID-19 pandemic on mental health as many community surveys have limited quality, rely on screening tests to measure mental health conditions and distress, and often use convenience samples. Moreover, robust surveys come mainly from high-income countries., Aim: To measure the prevalence of depressive disorders with onset during the pandemic in a community of a Lower-Middle-income country (LMIC)-Tunisia., Methods: Clinical semi-structured face-to-face interviews were carried out during the pandemic (September-December 2021) by medical doctors among a representative sample of the general population in the governorate of La Manouba, Tunisia. Psychiatric diagnoses were established according to DSM-IV., Results: The prevalence of Major Depressive Disorder (MDD) started or recurred after the pandemic was 5.66%. The factors associated with MDD were loss of job and considerably diminished income due to the pandemic (OR = 2.1, 95% CI [1.5, 2.9]) and the perception of having the family's financial situation below the Tunisian average (OR = 2.3, 95% CI [1.7, 3.2]). Female sex, marital status as separated/divorced, and having a COVID-19 infection were associated with MDD only in the overall sample and urban areas, but not in rural areas. Age and having loved ones who passed away due to COVID-19 were not associated with MDD., Conclusion: In Tunisia, the pandemic seems to have increased the risk of depression in people experiencing a precarious financial situation, also due to the pre-existing economic crisis. Specific local level factors, such as not establishing a rigid lockdown for an extended period, may have protected young people and allowed for better mourning in families suffering the loss of a loved one.

Objective: To compare the prevalence of postpartum depression (PPD) symptoms between high-income countries (HIC) and low- and middle-income countries (LMIC) during the COVID-19 pandemic., Methods: The PubMed, Embase, Virtual Health Library, Scopus, Web of Science, PsycINFO, and CINAHL databases were searched until October 2022 for studies that collected data during the pandemic. The metaprop command was used in the Stata statistical software version 12.0 to run a random-effects meta-analysis., Results: A total of 15 studies with 4,788 postpartum women were included. The overall prevalence of PPD symptoms was 31% (95%CI 21.85-40.99). The pooled prevalence of PPD symptoms among women from HIC (30.5% [95%CI 16.95-46.02]) did not differ significantly from that of women from LMIC (31.5% [95%CI 19.26-45.15]). However, studies that analyzed women up to 1 month after childbirth reported a lower prevalence of PPD symptoms (17.5% [95%CI 9.85-26.62]) compared to those that observed them up to 1 year after childbirth (38.3% [95%CI 33.96-42.83])., Conclusions: The prevalence of PPD symptoms was high across countries, regardless of human development index. This condition must be regularly tracked worldwide to assess, discuss, and recommend more assertive steps that may be implemented to address it based on the particular characteristics of each country., Competing Interests: This work was funded by Libbs Pharmaceuticals (LITT2104). The funders had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The authors report no conflicts of interest.

This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.

Introduction: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection., Materials and Methods: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy)., Results: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 - 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3'UTR polymorphism ( rs371194629 ) shows that the HLA-G 3'UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X 2  = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X 2  = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait ( rs11549407 C>T in the HBB gene), KIR2DS2/HLA -C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant ( rs35044562 A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3'UTR Del/Del genotype was independent from the other significant variables [OR M = 0.4 (95% CI 0.2 - 0.7), P M = 6.5 x 10 -4 ]., Conclusion: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mocci, Littera, Chessa, Campagna, Melis, Ottelio, Piras, Lai, Firinu, Tranquilli, Mascia, Vacca, Schirru, Lecca, Rassu, Cannas, Sanna, Carta, Sedda, Giuressi, Cipri, Miglianti, Perra and Giglio.)

SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs., (© 2021. The Author(s).)

Background: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection., Methods: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas., Results: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]., Conclusions: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Since February 2020, when coronavirus disease began to spread in Italy, general practitioners (GPs) were called to manage a growing number of health situations. The challenges experienced by Italian GPs remained unrevealed. This study aimed at exploring Italian GPs' care experiences and practices associated with critical incidents during the first wave of the pandemic. A qualitative study design involving the critical incident technique through an online survey was applied. Sociodemographic data and open-ended responses were collected. While participants' characteristics were analyzed through descriptive statistics, qualitative data were thematically analyzed employing the framework method. 149 GPs responded to the survey and 99 participants completed the survey (dropout rate = 33%). Eight themes emerged indicating factors related to the organization of the healthcare system and factors related to the clinical management of patients, that were perceived as impacting on the GPs' care provision. The analysis revealed difficulties in communicating with other local services. This, together with the lack of coordination among services, was reported as a major challenge. Primary care was perceived as having been undervalued and criticalities in the organization of GP courses, led in a bureaucratic fashion, posed at risk some trainees to be infected. The digital technologies adopted for remote patient consultations were seen as useful tools for daily practice helping the GPs to stay emotionally connected with their patients. Besides, the improvement in the GP-patient relationship in terms of solidarity between patients and doctors and compliance to rules, had a positive impact. Moreover, many respondents addressed the importance of professional collaboration and teamwork, in terms of both support in practical issues (to find PPE, diagnostics and guidelines) and emotional support. At the same time, the lack of resources (e.g., PPE, swabs) and of specific guidelines and protocols impacted on the care provision. Our findings suggest that GPs in Italy are at risk of being left behind within the epidemic management. Communication and coordination among services are essential and should be substantially improved, and primary care research should be initiated to collect the context-specific evidence necessary to enhance the system's preparedness to public health emergencies and the quality of primary care services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kurotschka, Serafini, Demontis, Serafini, Mereu, Moro, Carta and Ghirotto.)

Introduction: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infection could have direct involvement of the gastrointestinal tract, and in symptomatic cases, gastrointestinal symptoms (diarrhea, nausea/vomiting, abdominal pain) could be very common., Area Covered: In this article, we reviewed current-published data of the gastrointestinal aspects involved in SARS-CoV-2 infection, including prevalence and incidence of specific symptoms, the presumptive biological mechanism of GI infection, prognosis, clinical management, and public health-related concerns on the possible risk of oral-fecal transmission., Expert Opinion: Different clues point to direct virus infection and replication in mucosal cells of the gastrointestinal tract. In vitro studies showed that SARS-CoV-2 could enter into the gastrointestinal epithelial cells by the Angiotensin-Converting enzyme two membrane receptor. These findings, coupled with the identification of viral RNA found in stools of patients, clearly suggest that direct involvement of the gastrointestinal tract is very likely. This can justify most of the gastrointestinal symptoms but also suggest a risk for an oral-fecal route for transmission, additionally or alternatively to the main respiratory route.

Aim: SARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome., Method and Materials: We recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies., Results: Male sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0-0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8-8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7-220.6), Pc = 0.024]., Conclusion: The data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Littera, Campagna, Deidda, Angioni, Cipri, Melis, Firinu, Santus, Lai, Porcella, Lai, Rassu, Scioscia, Meloni, Schirru, Cordeddu, Kowalik, Serra, Ragatzu, Carta, Del Giacco, Restivo, Deidda, Orrù, Palimodde, Perra, Orrù, Conti, Balestrieri, Serra, Onali, Marongiu, Perra and Chessa.)