Respiratory Syncytial Virus Prevention through Monoclonal Antibodies: A Cross-Sectional Study on Knowledge, Attitudes, and Practices of Italian Pediatricians.

Respiratory Syncytial Virus (RSV) is a leading cause of morbidity and hospitalization in all infants. Many RSV vaccines and monoclonal antibodies (mAb) are currently under development to protect all infants, but to date preventive options are available only for preterms. In this study, we assessed the knowledge, attitudes, and practices towards RSV and the preventive use of mAb in a sample of Italian Pediatricians. An internet survey was administered through an internet discussion group, with a response rate of 4.4% over the potential respondents (No. 389 out of 8842, mean age 40.1 ± 9.1 years). The association of individual factors, knowledge, and risk perception status with the attitude towards mAb was initially inquired by means of a chi squared test, and all variables associated with mAb with p < 0.05 were included in a multivariable model calculating correspondent adjusted Odds Ratio (aOR) with 95% confidence intervals (95%CI). Of the participants, 41.9% had managed RSV cases in the previous 5 years, 34.4% had diagnosed RSV cases, and 32.6% required a subsequent hospitalization. However, only 14.4% had previously required mAb as immunoprophylaxis for RSV. Knowledge status was substantially inappropriate (actual estimate 54.0% ± 14.2, potential range 0-100), while the majority of participants acknowledged RSV as a substantial health threat for all infants (84.8%). In multivariable analysis, all these factors were characterized as positive effectors for having prescribed mAb (aOR 6.560, 95%CI 2.904-14.822 for higher knowledge score; aOR 6.579, 95%CI 2.919-14.827 for having a hospital background, and a OR 13.440, 95%CI 3.989; 45.287 for living in Italian Major Islands). In other words, reporting less knowledge gaps, having worked in settings with a higher risk of interaction with more severe cases, and being from Italian Major Islands, were identified as positive effectors for a higher reliance on mAb. However, the significant extent of knowledge gaps highlights the importance of appropriate medical education on RSV, its potential health consequences, and the investigational preventive interventions.

Invasive Meningococcal Disease and Meningococcal Serogroup B Vaccination in Adults and Their Offspring: Knowledge, Attitudes, and Practices in Italy (2019).

Despite its effectiveness in preventing invasive meningococcal disease (IMD), pediatric uptake of recombinant meningococcal vaccination for serogroup B meningitis (MenB) is low in Italy. This study aimed to investigate knowledge, attitudes, and practice (KAP) about IMD and the vaccine uptake for MenB from July to December 2019, in a sample collected from a series of local Facebook discussion groups from the provinces of Parma and Reggio Emilia (North-Eastern Italy; 337,104 registered users). A self-administered anonymous web-based questionnaire was used to collect demographics, knowledge status, perceived risk for contracting meningitis, attitude towards the utility of meningococcal vaccine, and willingness to receive/perform MenB vaccine in their offspring. In total, 541 parents returned a fully completed questionnaire (response rate of 1.6% of potential recipients), with a mean age of 39.2 years ± 6.3 (78.1% females). Meningococcal infection was identified as severe or highly severe by most participants (88.9%), while it was recognized as being frequent/highly frequent in the general population by 18.6% of respondents. The overall knowledge status was unsatisfactory (57.6% ± 33.6 of correct answers to the knowledge test). Even though 63.4% of participants were somewhat favorable to MenB/MenC vaccines, offspring's vaccination towards MenB was reported by only 38.7% of participants. In a binary logistic regression model, the male gender of respondents (adjusted odds ratio [aOR] 3.184, 95% confidence interval [95%CI] 1.772 to 5.721), living in a municipality >15,000 inhabitants (aOR 1.675, 95%CI 1.051 to 2.668), reporting a favorable attitude on meningococcus B vaccine (aOR 12.472, 95%CI 3.030 to 51.338), having been vaccinated against serogroup B (aOR 5.624, 95%CI 1.936 to 16.337) and/or serogroup C (aOR 2.652, 95%CI 1.442 to 4.872), and having previously vaccinated their offspring against serogroup C meningococcus (aOR 6.585, 95%CI 3.648 to 11.888) were characterized as positive effectors of offspring's vaccination. On the contrary, having a higher risk perception on vaccines was identified as the only negative effector (aOR 0.429, 95%CI 0.241 to 0.765). Our results hint towards extensive knowledge gaps on IMD and preventive interventions in the general population, suggesting that a positive attitude towards vaccines and vaccinations could be identified as the main effector also for MenB acceptance. Interventions in the general population aimed at improving confidence, compliance, and acknowledgment of the collective responsibility, as well as preventing actual constraints and the sharing of false beliefs on infectious diseases and their preventive measures, could therefore increase vaccination acceptance in both targeted individuals and their offspring.

Infodemiology of RSV in Italy (2017-2022): An Alternative Option for the Surveillance of Incident Cases in Pediatric Age?

The aim of this study was to evaluate whether or not online queries for Respiratory Syncytial Virus (RSV) retrieved by means of Google Trends™ and the Italian Wikipedia analysis program mirror the occurrence of influenza-like illnesses (ILI), as reported by the Italian Influenza Surveillance network (InfluNet). Estimated rates for ILI in the general population and in the age groups 0−4 years and 5−14 years were obtained for the influenza seasons 2017−2018 to 2020−2021. Similarly, a weekly fraction of online searches was retrieved for a series of terms associated with Respiratory Syncytial Virus. Next, trends for daily visualization of Italian Wikipedia Pages for Human Respiratory Syncytial Virus, Pneumonia, Bronchiolitis, Influenza, and Respiratory Failure were similarly retrieved. The correlation of all search terms with ILI was analyzed by means of Spearman's rank correlation analysis. Among search terms associated with the clinical diagnosis of Respiratory Syncytial Virus infections, the occurrence of ILI was highly correlated only with Bronchiolitis in the age group 0−4 years (ß 0.210, p = 0.028), while more generic search terms, such as Bronchitis, fever, influenza, and Pneumonia, were identified as effective predictors of ILI, in general and by age groups. In a regression analysis modeled with ILIs as the outcome variable, daily visualizations for the Wikipedia pages on Bronchiolitis were identified as negative predictors for ILI in general (ß = −0.152, p = 0.032), ILI in age group 0−4 years (ß = −0.264, p = 0.001) and 5−14 years (ß = −0.202, p = 0.006), while Influenza was characterized as a positive effector for ILIs in the age group 5−14 years (ß = 0.245, p = 0.001). Interestingly, not only were the search terms extensively correlated with one another, but all of them were also characterized by autocorrelation through a Durbin-Watson test (all estimates DW < 2.0) In summary, our study identified a complicated pattern of data visualization as no clear association between rates of ILI in pediatric age group 0−4 and 5 to 14 years was actually found. Finally, our data stress that the infodemiology option may be quite problematic for assessing the time trend of RSV infections in Italy until more appropriate reporting will be made available, by sharing estimates of Lower Respiratory Tract Infections, and through a more accurate characterization of younger age groups.

West Nile Virus Infection: A Cross-Sectional Study on Italian Medical Professionals during Summer Season 2022.

West Nile virus (WNV) has progressively endemized in large areas of continental Europe, and particularly in Northern Italy, in the Po River Valley. During summer season 2022, Italy experienced an unprecedented surge in incidence cases of WNV infections, including its main complications (West Nile fever (WNF) and West Nile neuroinvasive disease (WNND)). As knowledge, attitudes, and practices (KAP) of medical professionals may be instrumental in guaranteeing a prompt diagnosis and an accurate management of incident cases, we performed a cross-sectional study specifically on a sample of Italian medical professionals (1 August 2022-10 September 2022; around 8800 potential recipients). From a total of 332 questionnaires (response rate of 3.8%), 254 participating medical professionals were eventually included in the analyses. Knowledge status of participants was unsatisfying, as most of them exhibited knowledge gaps on the actual epidemiology of WNV, with similar uncertainties on the clinical features of WNF and WNND. Moreover, most of participants substantially overlooked WNV as a human pathogen when compared to SARS-CoV-2, TB, and even HIV. Interestingly, only 65.4% of respondents were either favorable or highly favorable towards a hypothetical WNV vaccine. Overall, acknowledging a higher risk perception on WNV was associated with individual factors such as reporting a seniority ≥ 10 years (adjusted odds ratio [aOR] 2.39, 95% Confidence interval [95%CI] 1.34 to 4.28), reporting a better knowledge score (aOR 2.92, 95%CI 1.60 to 5.30), having previously managed cases of WNV infections (aOR 3.65, 95%CI 1.14 to 14.20), being favorable towards a hypothetic vaccine (aOR 2.16, 95%CI 1.15 to 4.04), and perceiving WNV infections as potentially affecting daily activities (aOR 2.57, 95%CI 1.22 to 5.42). In summary, substantial knowledge gaps and the erratic risk perception collectively enlighten the importance and the urgency for appropriate information campaigns among medical professionals, and particularly among frontline personnel.

Potential Use of Exhaled Breath Condensate for Diagnosis of SARS-CoV-2 Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Reverse-transcriptase polymerase chain reaction (RT-qPCR) assays performed on respiratory samples collected through nasal swabs still represent the gold standard for COVID-19 diagnosis. Alternative methods to this invasive and time-consuming options are still being inquired, including the collection of airways lining fluids through exhaled breath condensate (EBC). MATERIALS AND METHODS: We performed a systematic review and meta-analysis in order to explore the reliability of EBC as a way to collect respiratory specimens for RT-qPCR for diagnosis of COVID-19. RESULTS: A total of 4 studies (205 specimens), were ultimately collected, with a pooled sensitivity of 69.5% (95%CI 26.8-93.4), and a pooled specificity of 98.3% (95%CI 87.8-99.8), associated with high heterogeneity and scarce diagnostic agreement with the gold standard represented by nasal swabs (Cohen's kappa = 0.585). DISCUSSION: Even though non-invasive options for diagnosis of COVID-19 are still necessary, EBC-based RT-qPCR showed scarce diagnostic performances, ultimately impairing its implementation in real-world settings. However, as few studies have been carried out to date, and the studies included in the present review are characterized by low numbers and low sample power, further research are requested to fully characterize the actual reliability of EBC-based RT-qPCR in the diagnosis of COVID-19.

Excess mortality in Mountain Areas of Emilia Romagna Region during the first months of SARS-CoV-2 pandemic: a "canary in the coal mine"?

BACKGROUND: Because of their remoteness, Mountain Communities (MC) have been considered at advantage when dealing with infectious diseases. However, earlier reports have identified MC among the hotspots for early spreading of COVID-19 pandemic. METHODS: Crude mortality rates (CMR) and Excess mortality rates (EMR) were calculated for 97 municipalities from MC in the Emilia Romagna Region, and resulting estimates were compared to the Parent Provinces. Notification and mortality rates for COVID-19 were also retrieved, and correlated with EMR estimates. RESULTS: During 2020, a CMR of 150.3/100,000 (95% Confidence Interval [95%CI] 117-185.4) was identified, with substantial heterogeneities between the 8 provinces of Emilia Romagna Region that were included in the analyses. A pooled EMR of +20.3% (95%CI 10.6-30.1) for MC and 19.9% (95%CI 9.5-30.3) was identified. The monthly estimates were quite heterogenous across the various provinces, ranging between -79.7% and +307.4% during the assessed timeframe. Higher estimates were identified in the months of March and April in MC, and during the months of April and May for Parent Provinces. In bivariate analysis, EM in MC was positively correlated with estimates in the parent province (Spearman's r = 0.201, p = 0.049), and also with notification rates for COVID- (i.e. Piacenza, Parma, Reggio Emilia, Modena, Bologna, Ravenna, Rimini, and Forlì Cesena) (r = 0.225, p = 0.045), and particularly with mortality rates for COVID-19 at provincial level (r = 0.372, p < 0.001). CONCLUSIONS: In summary, the study highlights that small geographical and population size, along with remoteness, did not play a substantial advantage for MC against the spread and mortality rate of COVID-19. On the other hand, as the surge of EM in MC anticipated a similar habit in Parent Provinces of several weeks, improved surveillance interventions are also urgently in need. (www.actabiomedica.it).

When a Neglected Tropical Disease Goes Global: Knowledge, Attitudes and Practices of Italian Physicians towards Monkeypox, Preliminary Results.

Monkeypox (MPX) has been regarded as a neglected tropic disease of Western and Central Africa since the early 70s. However, during May 2022, an unprecedent outbreak of MPX has involved most of European Countries, as well as North and South America. While the actual extent of this outbreak is being assessed by health authorities, we performed a pilot study on specific knowledge, attitudes, and practices (KAP) in a sample of Italian medical professionals (24-30 May 2022; 10,293 potential recipients), focusing on Occupational Physicians (OP), Public Health Professionals (PH), and General Practitioners (GP), i.e., medical professionals more likely involved in the early management of incident cases. More specifically, we inquired into their attitude on the use of variola vaccine in order to prevent MPX infection. From a total of 566 questionnaire (response rate of 5.5%), 163 participants were included in the final analyses. Knowledge status was quite unsatisfying, with substantial knowledge gaps on all aspect of MPX. In turn, analysis of risk perception suggested a substantial overlooking of MPX as a pathogen, particularly when compared to SARS-CoV-2, TB, HIV, and HBV. Overall, 58.6% of respondents were somehow favorable to implement variola vaccination in order to prevent MPX, and the main effectors of this attitude were identified in having been previously vaccinated against seasonal influenza (adjusted Odds Ratio [aOR] 6.443, 95% Confidence Interval [95%CI] 1.798-23.093), and being favorable to receive variola vaccine (aOR 21.416; 95%CI 7.290-62.914). In summary, the significant extent of knowledge gaps and the erratic risk perception, associated collectively stress the importance of appropriate information campaigns among first-line medical professionals.

Knowledge, Attitudes and Practices towards SARS-CoV-2 vaccination among morbid obese individuals: a pilot study.

BACKGROUND AND AIM: Vaccinations have dramatically impacted on the ongoing pandemic of COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As morbid obese (MO) individuals are at high risk for severe complications, their acceptance of SARS-CoV-2 vaccines is of certain public health interest. METHODS: We investigated the knowledge, attitudes and eventual acceptance of SARS-CoV-2/COVID-19 vaccination among MO individuals either in waiting list, or recipients of bariatric surgery from a reference center (Parma University Hospital) shortly before the inception of the Italian mass vaccination campaign (March 2021). Data were collected through a web-based questionnaire. Association of individual factors with acceptance of SARS-CoV-2 vaccine was assessed by means of a logistic regression analysis with eventual calculation of adjusted Odds Ratios (aOR) and corresponding 95% Confidence Intervals (95%CI). RESULTS: Adequate, general knowledge of SARS-CoV-2/COVID-19 was found in the majority of MO patients. High perception of SARS-CoV-2 risk was found in around 80% of participants (79.2% regarding its occurrence, 73.6% regarding its potential severity). Acceptance of SARS-CoV-2/COVID-19 vaccination was reported by 65.3% of participants, and was more likely endorsed by MO patients who were likely to accept some sort of payment/copayment (aOR 5.783; 1.426; 23.456), or who were more likely towards a vaccination mandate (aOR 7.920; 1.995; 31.444). CONCLUSIONS: Around one third of the MO individuals among potential recipient of bariatric surgery exhibited some significant hesitancy towards SARS-CoV-2 vaccine, and a rational approach may fail to capture and address specific barriers/motivators in this subset of individuals, stressing the importance for alternative interventions. (www.actabiomedica.it).

SARS-CoV-2 pandemic and Construction Industry: insights from Italian data.

Construction industry (CoI) has been severely affected by SARS-CoV-2 pandemic since its onset, as it delayed or even halted construction projects, either directly or indirectly, through interruption of the supply chain, or shortage of workers (1). Moreover, Construction Workers (CW) has been associated with high level of infection and hospitalization (2-3). Albeit CoI and its workforce globally share several characteristics (e.g. relatively low socio-economic status and education level; high share of migrant workforce and/or ethnic minorities; often inappropriate adherence to up-to-date health and safety standards etc.) (4-5), both are significantly affected by local infrastructure (e.g. roads, hospitals, housing) and safety legislations. Unfortunately, most of available data on SARS-CoV-2 in CoI focus on United States (2-3,6), while more limited evidences from other High-Income Countries (7-9). In this regard, a retrospective analysis of Italian data may be of certain interest. To begin with, Italy had an early implementation of lockdown measures, i.e. February 2021 (10). Second, following the economic crisis kicked off in 2008 by US subprime housing market, Italian CoI workforce collapsed from 2 million people in 2008, to around 1.3 million in 2019 (4-5); as a consequence, the majority of Italian CW are either self-employed or employed in small sized enterprises (< 10 employees) (5), that are only limitedly able to cope with the COVID-19 safety requirements (1). Third, the smaller size of enterprises enhances the contacts between employees, that often occur even outside the construction yards (2-3), potentially enhancing the spread of SARS-CoV-2 infection from and within this community. Fourth, nearly all Italian CW are required to fill a mandatory insurance for occupational illness and injuries, and data on compensation claims are regularly provided by the competent National Insurance (INAIL), allowing their retrospective analysis. According to available data, a total of 176,925 compensation claims for work-related SARS-CoV-2 infections have been reported up to June 30th, 2021 (https://www.inail.it/cs/internet/comunicazione/covid-19-prodotti-informativi/report-covid-19.html). Of them, a total of 1,415 occurred in CW (0.8% of total claims), with a cumulative incidence of 1.04 per 1,000 employees, compared to 7.69 per 1,000 employed in other economic sectors. Monthly incidence rate among CW and among the general population were not correlated (R = -0.45, p = 0.097). As CoI is traditionally a "male" industry, but official data do not provide accurate information on the demographics of occupational subgroups, we calculated corresponding Risk Ratio (RR) and 95% Confidence Intervals (95%CI) for SARS-CoV-2 compensation claims assuming that (a) substantially all compensated CW were of male gender; (b) the reference group was represented by Italian male workforce. Briefly, RR for CoI ranged between 0.241 (95%CI 0.204-0.285) in April 2020 and 0.358 (95%CI 0.339-0.377) in June 2021, with a sudden surge after December 2020 i.e. compared to other occupational groups, CW seemly exhibit a substantially lower risk for SARS-CoV-2 compensation claims. When focusing on SARS-CoV-2 related deaths, a total of 48 compensation claims were retrieved for CoI, from a total of 682 work-related events (7.1%). Corresponding case fatality ratio (CFR) was 3.42% compared to 1.03% in the whole of workers of male gender, with a RR equals to 3.287 (95%CI 2.460-4.392), confirming a substantially higher risk for a severe outcome in CW compared to other occupational groups. The relatively low risk for SARS-CoV-2 work-related infection in Italian CW has been originally described by Marinaccio et al. (2020) (8), and several explanations may be suggested. Firstly, during the first months of the pandemic most construction yards were halted, with a substantial reduction of active workforce (i.e. around 0.5 million people compared to 1.3 before the lockdown) (2,8). However, raw data suggest that most of cases occurred well after the lockdown, following the resurgence of SARS-CoV-2 pandemic during the second half of 2020 (i.e. 81.5% of all cases in construction workers were notified since September 1st, 2020). Moreover, Italian Law n. 77/2020 (17 July 2020) has introduced a 110% tax deduction for energy efficiency, anti-seismic interventions and photovoltaic plans that has significantly propelled CoI, with a sustained rebound in active workforce. In this regard, the better performance of CoI during 2021 have presumptively contributed to the increased occurrence of new cases since January 2021. Second, CW mostly work outdoors, and close interactions between CW are not regularly required in the construction yards (1-2,7), reducing the risk for interpersonal spreading of SARS-CoV-2. Third, it is reasonable that the small size of Italian construction enterprises may have created a sort of "bubble" effect, with CW forming a cohesive unit within a single enterprise, that allows individuals to increase their close, physical social interactions while potentially limiting the risk of infection through the exclusivity of the bubble. The increased CFR for CW compared to other occupational groups may be similarly explained through the specificities of the Italian CoI. While earlier reports hinted towards social deprivation as the main cause of higher hospitalization rates among CW (2-3), Italian CoI is characterized by a very high share of male individuals from older age groups, often reporting well-known risk factor for a worse prognosis of COVID-19 such as smoking, obesity, alcohol consumption, but also pre-existing respiratory disorders associated with the occupational exposure (4-5). In other words, the individual risk factors affecting a significant share of Italian CW may explain their increased risk for a dismal outcome compared to other occupational groups. Even though our estimates are both highly dependent on the quality of source data and affected by the significant lack of detailed demographic information, they suggest that even though SARS-CoV-2 is simultaneously affecting all workplaces, the course of the ongoing pandemic in occupational settings may be considerably influenced by the specific background and demographics of involved groups. High-quality data from various occupational and geographic settings are therefore required in order to improve our understanding of risk factors and appropriate preventive measures.

Respiratory Syncytial Virus: Knowledge, Attitudes and Beliefs of General Practitioners from North-Eastern Italy (2021).

Respiratory syncytial virus (RSV) is a lead cause of morbidity and hospitalizations in infants. RSV vaccines are currently under development, and preventive options are limited to monoclonal antibodies (mAb). We assessed the knowledge, attitudes and practices for RSV in a sample of general practitioners (GPs) from north-eastern Italy (2021), focusing on the risk perception for infants (age < 8 years) and its potential effectors. We administered an internet survey to 543 GPs, with a response rate of 28.9%. Knowledge status was unsatisfactory, with substantial knowledge gaps found on the epidemiology of RSV and its prevention through mAb. The main effectors of risk perception were identified as having a background in pediatrics (adjusted odds ratio (aOR): 55.398 and 95% confidence interval (95% CI): 6.796-451.604), being favorable towards RSV vaccines when available (aOR: 4.728, 95% CI: 1.999-11.187), while having previously managed an RSV case (aOR: 0.114, 95% CI: 0.024-0.552) and previously recommended hospitalization for cases (aOR: 0.240, 95% CI: 0.066-0.869) were identified as negative effectors. In summary, the significant extent of knowledge gaps and the erratic risk perception, associated with the increasing occurrence in RSV infections, collectively stress the importance of appropriate information campaigns among primary care providers.

Excess Mortality on Italian Small Islands during the SARS-CoV-2 Pandemic: An Ecological Study.

Small islands have been considered at an advantage when dealing with infectious diseases, including COVID-19, but the evidence is still lacking. Crude mortality rates (CMRs) and excess mortality rates (EMRs) were calculated for 35 municipalities on the Italian small islands for 2020 and 2021, and the corresponding estimates were compared to those of the parent provinces and the national estimates. Notification rates for COVID-19 were retrieved, but detailed data at the municipality level were not available. A relatively low CMR (1.069 per 100 per year, 95% confidence interval [95% CI] 0.983-1.164) was identified in 2020, compared to 1.180, 95% CI 1.098-1.269 for 2021. EMRs of small islands ranged between -25.6% and +15.6% in 2020, and between -13.0% and +20.9% in 2021, with an average gain of +0.3% (95% CI -5.3 to +5.8) for the entirety of the assessed timeframe, and no substantial differences between 2020 and 2021 (pooled estimates of -4.1%, 95% CI -12.3 to 4.1 vs. 4.6%, 95% CI -3.1 to 12.4; p = 0.143). When dealing with COVID-19 notification rates, during the first wave, parent provinces of Italian small islands exhibited substantially lower estimates than those at the national level. Even though subsequent stages of the pandemic (i.e., second, third, and fourth waves) saw a drastic increase in the number of confirmed cases and CMR, estimates from small islands remained generally lower than those from parent provinces and the national level. In regression analysis, notification rates and mortality in the parent provinces were the main effectors of EMRs in the small islands (ß = 0.469 and ß = 22.768, p < 0.001 and p = 0.007, respectively). Contrarily, the management of incident cases in hospital infrastructures and ICUs was characterized as a negative predictor for EMR (ß = -11.208, p = 0.008, and -59.700, p = 0.003, respectively). In summary, the study suggests a potential role of small geographical and population size in strengthening the effect of restrictive measures toward countering the spread and mortality rate of COVID-19.

Antigen Detection Tests for SARS-CoV-2: a systematic review and meta-analysis on real world data.

Background and aim Rapid antigen detection (RAD) tests on nasopharyngeal specimens have been recently made available for SARS-CoV-2 infections, and early studies suggested their potential utilization as rapid screening and diagnostic testing. The present systematic review and meta-analysis was aimed to assess available evidence and to explore the reliability of antigenic tests in the management of the SARS-CoV-2 pandemic. MATERIALS AND METHODS: We reported our meta-analysis according to the PRISMA statement. We searched Pubmed, Embase, and pre-print archive medRxiv.og for eligible studies published up to November 5th, 2020. Raw data included true/false positive and negative tests, and the total number of tests. Sensitivity and specificity data were calculated for every study, and then pooled in a random-effects model. Heterogeneity was assessed using the I2 measure. Reporting bias was assessed by means of funnel plots and regression analysis. RESULTS: Based on 25 studies, we computed a pooled sensitivity of 72.8% (95%CI 62.4-81.3), a specificity of 99.4% (95%CI 99.0-99.7), with high heterogeneity and risk of reporting bias. More precisely, RAD tests exhibited higher sensitivity on samples with high viral load (i.e. <25 Cycle Threshold; 97.6%; 95%CI 94.1-99.0), compared to those with low viral load (≥25 Cycle Threshold; 43.6%; 95% 27.6-61.1). DISCUSSION: As the majority of collected reports were either cohort or case-control studies, deprived of preventive power analysis and often oversampling positive tests, overall performances may have been overestimated. Therefore, the massive referral to antigenic tests in place of RT-qPCR is currently questionable, and also their deployment as mass screening test may lead to intolerable share of missing diagnoses. On the other hand, RAD tests may find a significant role in primary care and in front-line settings (e.g. Emergency Departments). (www.actabiomedica.it).

SARS-CoV-2-Legionella Co-Infections: A Systematic Review and Meta-Analysis (2020-2021).

Legionnaires' Disease (LD) is a severe, sometimes fatal interstitial pneumonia due to Legionella pneumophila. Since the inception of the SARS-CoV-2 pandemic, some contradictory reports about the effects of lockdown measures on its epidemiology have been published, but no summary evidence has been collected to date. Therefore, we searched two different databases (PubMed and EMBASE) focusing on studies that reported the occurrence of LD among SARS-CoV-2 cases. Data were extracted using a standardized assessment form, and the results of such analyses were systematically reported, summarized, and compared. We identified a total of 38 articles, including 27 observational studies (either prospective or retrospective ones), 10 case reports, and 1 case series. Overall, data on 10,936 SARS-CoV-2 cases were included in the analyses. Of them, 5035 (46.0%) were tested for Legionella either through urinary antigen test or PCR, with 18 positive cases (0.4%). A pooled prevalence of 0.288% (95% Confidence Interval (95% CI) 0.129-0.641), was eventually calculated. Moreover, detailed data on 19 co-infections LD + SARS-CoV-2 were obtained (males: 84.2%; mean age: 61.9 years, range 35 to 83; 78.9% with 1 or more underlying comorbidities), including 16 (84.2%) admissions to the ICU, with a Case Fatality Ratio of 26.3%. In summary, our analyses suggest that the occurrence of SARS-CoV-2-Legionella infections may represent a relatively rare but not irrelevant event, and incident cases are characterized by a dismal prognosis.

Impact of lockdown and non-pharmaceutical interventions on the epidemiology of Legionnaires' disease.

BACKGROUND AND AIM: In order to cope with the requirements of COVID-19 pandemic and prevent overwhelming of the healthcare systems, during 2020 social distancing measures were proposed, and generalized lockdown. Aim of our study is to ascertain whether non-pharmaceutical intervention did have any impact on the epidemiology of Legionnaires' disease (LD), a respiratory infectious disease without interhuman spreading. METHODS: Official national reports from 4 index countries in European Union (i.e. Germany, France, Italy, and Spain) were retrieved. The study included all cases notified during 2020 COVID-19 outbreak, versus the cases referred during the same period in 2019. Subgroup analyses for hospital-associated and travel-associated LD cases, as well as for lethality estimates were performed. RESULTS: A sustained drop for incidence rate was confirmed, at EU-level (3.5 per 100,000 vs. 5.3 per 100,000) as well as in the national estimates. The decrease was particularly evident in Italy (RR 0.880, 95%CI 0.839 to 0.905), despite a transient surge in notification rates during the month of June, 2020. Subgroup analyses demonstrated a fall in travel-associated cases (-66.8% at EU level), while hospital-associated cases decreased in absolute number when compared to 2019, but where substantially stable in terms when compared to EU estimates. While Case Fatality Ratio increased in comparison with 2019, no significant trend was similarly identified in comparison to EU estimates.  Conclusions. Lockdown measures have impacted on the epidemiology of LD in Europe during 2020, but some heterogeneities were identified both across the assessed countries, and the various subgroup. Even though the absolute number of total cases did substantially decrease in 2020 compared to 2019, the effect of non-pharmaceutical interventions was mostly indirect, through a reduced interaction of individuals with environments at potentially high-risk for human infections (e.g. hospitals, accommodation sites, etc.).

Occurrence of SARS-CoV-2 infection among healthcare personnel: results from an early systematic review and meta-analysis.

BACKGROUND: SARS-CoV-2 infection has become a global public health concern globally. Even though Healthcare Workers (HCWs) are supposedly at increased risk for SARS-CoV-2 infection, to date no pooled evidence has been collected. MATERIALS AND METHODS: We searched online electronic databases (PubMed, Embase, medRxiv.org for pre-prints) for all available contribution (up to May 20, 2019). Two Authors independently screened articles and extracted the data. The pooled prevalence of SARS-CoV-2 was analyzed using the random-effects model. The possible sources of heterogeneity were analyzed through subgroup analysis, and meta-regression. RESULTS: The overall pooled prevalence of SARS-CoV-2 was 3.5% (95%CI 1.8-6.6) for studies based on molecular assays, 5.5% (95%CI 2.1-14.1) for studies based on serological assays, and 6.5% (95%CI 2.5-15.6) for point-of-care capillary blood tests. Among subgroups, serological tests identified higher risk for SARS-CoV-2 seropositivity in physicians than in nurses (OR 1.436, 95%CI 1.026 to 2.008). Regression analysis indicated the possible presence of publication bias only for molecular tests (t -3.3526, p-value 0.002648). CONCLUSIONS: The overall pooled prevalence of SARS-CoV-2 was lower than previously expected, but available studies were affected by significant heterogeneity, and the molecular studies by significant publication bias. Therefore, further high-quality research in the field is warranted.

RT-qPCR assays based on saliva rather than on nasopharyngeal swabs are possible but should be interpreted with caution: results from a systematic review and meta-analysis.

BACKGROUND AND AIM OF THE WORK: The ongoing pandemic has elicited an increasing interest regarding the SARS-CoV-2 viral RNA detection in saliva specimens rather than through nasopharyngeal swabs. Our aim was to conduct a meta-analysis on the sensitivity and specificity of SARS-CoV-2 viral RNA detection through RT-qPCR based on salivary specimens compared to conventional nasopharyngeal swabs. METHODS: We reported our meta-analysis according to the PRISMA statement. We searched Pubmed, Embase, and pre-print archive medRxiv.og for eligible studies published up to June 1st, 2020. Raw data included true/false positive and negative tests, and the total number of tests. Sensitivity and specificity data were calculated for every study, and then pooled in a random-effects model. Heterogeneity was assessed using the I2 measure. Reporting bias was assessed by means of funnel plots and regression analysis. RESULTS: The systematic review eventually retrieved 14 studies including a total of 15 estimates, the were included in quantitative synthesis. We found a pooled specificity of 97.7% (95%CI 93.8-99.2) and a pooled sensitivity of 83.4% (95%CI 73.1-90.4), with an overall agreement assessed by means of Cohen's kappa equals to 0.750, 95%CI 0.62-0.88 (i.e. moderate agreement), with high heterogeneity and risk of reporting bias. CONCLUSIONS: In conclusion, diagnostic tests based on salivary specimens are somewhat reliable, but relatively few studies have been carried out. Moreover, such studies are characterized by low numbers and low sample power. Therefore, the of salivary samples is currently questionable for clinical purposes and cannot substitute other more conventional RT-qPCR based on nasopharyngeal swabs.