Still Unanswered Questions About SARS-CoV-2 Mortality and Future Directions for Occupational Medicine.

The article discusses a recent study on mortality attributable to COVID-19 in Italy and the need for further analysis. The study used a reliable methodology to estimate excess deaths due to the pandemic. However, there are still questions about the specific effects of COVID-19 compared to other factors, such as delayed or missing access to treatment for other illnesses. Analyzing the time course of excess deaths could reveal such effects. There are also open questions about how COVID-19 deaths are classified and reported, which could lead to over or under-diagnosing cases. The article notes that occupational physicians have played an important role in preventing the spread of COVID-19 among workers. A recent study found that personal protective equipment (PPE), particularly masks, effectively reduced the risk of infection among healthcare workers. However, it is still unclear whether Occupational Medicine should incorporate infectious diseases as a major concern or return to its historically agnostic attitude toward communicable diseases. More data on mortality from specific diseases will be needed for further analysis and understanding of the pandemic's effects on mortality rates in Italy.

Safety of heterologous ChAdOx1-S/BNT162b2 primary schedule versus homologous BNT162b2 vaccination: Insights from an Italian post-marketing study, 2021.

During COVID-19 vaccination campaign, possible ChAdOx1-S-associated risks of thrombosis with thrombocytopenia syndrome led to implement ChAdOx1-S/BNT162b2 heterologous vaccination, despite the limited information on its reactogenicity and safety. We conducted a prospective observational post-marketing surveillance study to assess the safety of this heterologous schedule. A casually selected sample of recipients (n: 85; age: 18-60 years) of ChAdOx1-S/BNT162b2 at the vaccination hub of the Foggia Hospital, Italy, was matched with an equal sample of recipients of homologous BNT162b2. Safety was evaluated 7 days, 1 month and 14 weeks after the primary vaccination series using an adapted version of the "V-safe active surveillance for COVID-19 vaccine safety" CDC standardized questionnaire. After 7 days, local reactions were highly frequent (>80%) in both groups, and systemic reactions were less common (<70%). Moderate or severe pain at the injection site (OR = 3.62; 95%CI, 1.45-9.33), moderate/severe fatigue (OR = 3.40; 95%CI, 1.22-9.49), moderate/severe headache (OR = 4.72; 95%CI, 1.37-16.23), intake of antipyretics (OR = 3.05; 95 CI%, 1.35-6.88), inability to perform daily activities and work (OR = 2.64; 95%CI, 1.24-5.62) were significantly more common with heterologous than homologous vaccination. No significant difference in self-reported health status was recorded 1 month or 14 weeks after the second dose with BNT162b2 or ChAdOx1-S/BNT162b2. Our study confirms the safety of both heterologous and homologous vaccination, with a slight increase in some short-term adverse events for the heterologous regimen. Therefore, administering a second dose of a mRNA vaccine to the recipients of a previous dose of viral vector vaccine may have represented an advantageous strategy to improve flexibility and to accelerate the vaccination campaign.

Long-Term SARS-CoV-2 Antibody Seroprevalence in Blood Donors, Italy.

We evaluated SARS-CoV-2 antibody response in voluntary blood donors in Italy at different timepoints. Immediately after lockdown easing, 908/25,657 donors (3.5%) had low IgG titers against nucleocapsid. In the next 2 years, titers increased despite few COVID-19 symptoms. On multivariate analysis, allergic rhinitis was associated with reduced risk for symptomatic COVID-19.

The relative prevalence of the Omicron variant within SARS-CoV-2 infected cohorts in different countries: A systematic review.

The Omicron variant of SARS-CoV-2 was detected in October 2021 and exhibited high transmissibility, immune evasion, and reduced severity when compared to the earlier variants. The lesser vaccine effectiveness against Omicron and its reduced severity created vaccination hesitancy among the public. This review compiled data reporting the relative prevalence of Omicron as compared to the early variants to give an insight into the existing variants, which may shape the decisions regarding the targets of the newly developed vaccines. Complied data revealed more than 90% prevalence within the infected cohorts in some countries. The BA.1 subvariant predominated over the BA.2 during the early stages of the Omicron wave. Moreover, BA.4/BA.5 subvariants were detected in South Africa, USA and Italy between October 2021 and April 2022. It is therefore important to develop vaccines that protect against Omicron as well as the early variants, which are known to cause more severe complications.

Web-based surveillance of respiratory infection outbreaks: retrospective analysis of Italian COVID-19 epidemic waves using Google Trends.

Introduction: Large-scale diagnostic testing has been proven insufficient to promptly monitor the spread of the Coronavirus disease 2019. Electronic resources may provide better insight into the early detection of epidemics. We aimed to retrospectively explore whether the Google search volume has been useful in detecting Severe Acute Respiratory Syndrome Coronavirus outbreaks early compared to the swab-based surveillance system. Methods: The Google Trends website was used by applying the research to three Italian regions (Lombardy, Marche, and Sicily), covering 16 million Italian citizens. An autoregressive-moving-average model was fitted, and residual charts were plotted to detect outliers in weekly searches of five keywords. Signals that occurred during periods labelled as free from epidemics were used to measure Positive Predictive Values and False Negative Rates in anticipating the epidemic wave occurrence. Results: Signals from "fever," "cough," and "sore throat" showed better performance than those from "loss of smell" and "loss of taste." More than 80% of true epidemic waves were detected early by the occurrence of at least an outlier signal in Lombardy, although this implies a 20% false alarm signals. Performance was poorer for Sicily and Marche. Conclusion: Monitoring the volume of Google searches can be a valuable tool for early detection of respiratory infectious disease outbreaks, particularly in areas with high access to home internet. The inclusion of web-based syndromic keywords is promising as it could facilitate the containment of COVID-19 and perhaps other unknown infectious diseases in the future.

[A national overview of the topics covered by young people in epidemiology: a comparison before and after the Covid-19.] / Un quadro nazionale delle tematiche trattate dai giovani in epidemiologia: un confronto prima e dopo il Covid-19.

INTRODUCTION: Epidemiology is increasingly involved on a wide variety of topics and to engage different professionals and disciplines in an increasingly active way. A fundamental role is played by young researchers active in Italian epidemiology who create opportunities for meeting and discussion, in the name of multidisciplinarity and integration of different skills. OBJECTIVE: The aim of this paper is to provide a detailed description of the topics most frequently studied in epidemiology by young people and to highlight any changes in these topics in the pre- and post-Covid-19 workplaces. METHODS: All abstracts submitted in the years 2019 and 2022 by young participants in the Maccacaro Prize, an annual award aimed at Italian association of epidemiology (Aie) conference addressed to people under 35 years of age, were considered. In addition to the comparison of the topics, a comparison of the related work structures and their geographical location was carried out by grouping the research centres into three Italian geographical regions: north, centre and south/islands. RESULTS: Between 2019 and 2022, the number of abstracts participating in the Maccacaro Prize increased. The interest in topics related to infectious diseases, vaccines, and pharmaco-epidemiology has sharply increased, while in environmental and maternal and child epidemiology it has moderately increased. Social epidemiology, health promotion and prevention, as well as clinical and evaluative epidemiology, have experienced a decrease in interest. Finally, after analysing the geographical distribution of reference centres, it was discovered that certain regions, such as Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany and Latium, have a strong and consistent presence of young people in the field of epidemiology. Conversely, there is a small number of young professionals working in this field in other Italian regions, especially in Southern regions. CONCLUSIONS: The pandemic has changed our personal and working habits, but it has also played a fundamental role in making epidemiology known. The increase in young people joining an association such as the Aie is a clear sign of the growing interest in this discipline.

Risk perception, knowledge about SARS-CoV-2, and perception towards preventive measures in Italy: a nationwide cross-sectional study.

Introduction: After COVID-19 outbreak, governments adopted several containment measures. Risk perception and knowledge may play a crucial role since they can affect compliance with preventive measures. This study aimed to explore the extent and the associated factors of risk perception, knowledge regarding SARS-CoV2, and perception towards preventive measures among the Italian population. Methods: A nationwide cross-sectional study involving adults was conducted in April-May 2021: an online survey was distributed through social media. The outcomes were: Knowledge Score (KS) (0 to 100%: higher scores correspond to higher COVID-19 related knowledge); Risk Perception Score (RPS) (1 to 4: higher values indicate higher concern); Preventive measures Perception Score (PPS) (1 to 4: higher values indicate higher confidence). Multivariable regression models were performed. Results: A total of 1120 participants were included. Median KS was 79.5% (IQR = 72.7%-86.4%). Lower education and poor economic conditions were negatively associated with the KS. Median RPS was 2.8 (IQR = 2.4-3.2). Female gender, sharing house with a fragile person, suffering from a chronic disease, having a family member/close friend who contracted SARS-CoV-2 infection were positively associated with the RPS. Median PPS was 3.1 (IQR = 2.8-3.4). Lower educational level was negatively associated with the PPS. Vaccine hesitancy was negatively associated with all three outcomes. The three scores were positively associated with each other. Conclusions: Fair levels of knowledge, risk perception and perception towards preventive measures were reported. Reciprocal relationships between the outcomes and a relevant relationship with vaccine hesitancy were highlighted. Further investigations should be focused on studying underlying determinants and consequences.

Acceptance of recommended vaccinations during pregnancy: a cross-sectional study in Southern Italy.

Background: Vaccine administration is a recommended, safe, and effective measure to protect pregnant women against vaccine-preventable diseases (VPDs). Despite available guidance, maternal immunization rates for vaccination against influenza and with the reduced antigen content tetanus-diphtheria-acellular pertussis vaccine (Tdap) in Italy remain incredibly low. The primary goal of the study was to explore what Italian pregnant women knew about VPDs and immunization during pregnancy and what factors affected their decision to be vaccinated. Methods: This cross-sectional study took place between October 2021 and April 2022 in the Southern part of Italy. All consecutive pregnant women, from those attending the selected facilities on randomly selected days, were approached to request participation. The inclusion criteria for participation were age ≥18 years, the ability to understand, speak, and read Italian, and being pregnant at any gestational age. The questionnaire, using a combination of checkboxes and free text answers, consisted of 32 items divided into five parts and lasted ~10 min. Results: The results showed that 61% knew that the influenza vaccine is recommended and 48.7% knew that influenza could be risky during pregnancy; 74.1% wrongly reported that the Measles-Mumps-Rubella (MMR) vaccine is recommended during pregnancy. Seven out of 10 pregnant women believed that strong evidence supported the safety of vaccinations during pregnancy, and more than half (55.6%) thought they were at increased risk of severe illness with COVID-19. Women in the sample believed that vaccines received during pregnancy pose a risk of adverse events to the unborn child with a median value of 6 (IQR 3-9), on a scale ranging from 1 to 10. Similarly, the fear of contracting pertussis and influenza during pregnancy showed a median value of 6 (IQR 3-9) and 5 (IQR 3-8), respectively. Only 21.1% and 36.5% of women received influenza and Tdap vaccines during pregnancy. Conclusion: Unrealistic risk perception with a negative attitude toward vaccines in pregnancy and a low percentage of vaccinated pregnant women confirm the urgency of training women to make informed choices to increase overall vaccine uptake.

A COVID-19 Infection Model Considering the Factors of Environmental Vectors and Re-Positives and Its Application to Data Fitting in Japan and Italy.

COVID-19, which broke out globally in 2019, is an infectious disease caused by a novel strain of coronavirus, and its spread is highly contagious and concealed. Environmental vectors play an important role in viral infection and transmission, which brings new difficulties and challenges to disease prevention and control. In this paper, a type of differential equation model is constructed according to the spreading functions and characteristics of exposed individuals and environmental vectors during the virus infection process. In the proposed model, five compartments were considered, namely, susceptible individuals, exposed individuals, infected individuals, recovered individuals, and environmental vectors (contaminated with free virus particles). In particular, the re-positive factor was taken into account (i.e., recovered individuals who have lost sufficient immune protection may still return to the exposed class). With the basic reproduction number R0 of the model, the global stability of the disease-free equilibrium and uniform persistence of the model were completely analyzed. Furthermore, sufficient conditions for the global stability of the endemic equilibrium of the model were also given. Finally, the effective predictability of the model was tested by fitting COVID-19 data from Japan and Italy.

The Immune Response to SARS-CoV-2 Vaccine in a Cohort of Family Pediatricians from Southern Italy.

In Italy, from January 2021, the Ministry of Health indicated a vaccination plan against COVID for frail patients and physicians based on a three-dose scheme. However, conflicting results have been reported on which biomarkers permit immunization assessment. We used several laboratory approaches (i.e., antibodies serum levels, flow cytometry analysis, and cytokines release by stimulated cells) to investigate the immune response in a cohort of 53 family pediatricians (FPs) at different times after the vaccine. We observed that the BNT162b2-mRNA vaccine induced a significant increase of specific antibodies after the third (booster) dose; however, the antibody titer was not predictive of the risk of developing the infection in the six months following the booster dose. The antigen stimulation of PBMC cells from subjects vaccinated with the third booster jab induced the increase of the activated T cells (i.e., CD4+ CD154+); the frequency of CD4+ CD154+ TNF-α+ cells, as well as the TNF-α secretion, was not modified, while we observed a trend of increase of IFN-γ secretion. Interestingly, the level of CD8+ IFN-γ+ (independently from antibody titer) was significantly increased after the third dose and predicts the risk of developing the infection in the six months following the booster jab. Such results may impact also other virus vaccinations.

[Open ICU in pandemic phase Sars-CoV-2: the partial reopening of family visits in an ICU in Northern Italy]. / Terapia intensiva 'aperta' in fase pandemica Sars-CoV-2: esperienza di riapertura parziale delle visite dei familiari in una Terapia Intensiva del Nord Italia.

. Open ICU in pandemic phase Sars-CoV-2: the partial reopening of family visits in an ICU in Northern Italy. INTRODUCTION: During the Covid-19 pandemic, policies restricting family visits to health care facilities were commonly adopted, negatively impacting on patients, families and on the care team. AIM: To describe the reorganisation of a 23-bed Intensive Care Unit in Northern Italy for partial reopening to visits during the pandemic. METHODS: The reorganisation involved several phases: I) feasibility analysis, II) thawing out resistances; III) identifying behavioural, IV) organisational and structural indications for family access in the Covid area; V) fostering communication to guarantee information and emotional support for family members and VI) assessing, through an anonymous questionnaire, the degree of agreement on the impact of the presence of family members on health care team, patient and perception of safety. RESULTS: The majority of the relatives felt that the visit at the patient's bedside had a beneficial effect and reduced their anxiety. Almost all family members felt protected from the Covid-19 infectious risk. Healthcare staff also felt that the presence of family members contributed positively to the relationship with the patient. No family members contracted the Covid-19 infection during the evaluation period. CONCLUSIONS: Reopening access to family members during the Covid-19 period is possible, sustainable and beneficial. The use of flexible and motivational management principles by the coordinator were crucial in ensuring a family-centred approach during the pandemic.

Estimating Overall and Cause-Specific Excess Mortality during the COVID-19 Pandemic: Methodological Approaches Compared.

During the COVID-19 pandemic, excess mortality has been reported worldwide, but its magnitude has varied depending on methodological differences that hinder between-study comparability. Our aim was to estimate variability attributable to different methods, focusing on specific causes of death with different pre-pandemic trends. Monthly mortality figures observed in 2020 in the Veneto Region (Italy) were compared with those forecasted using: (1) 2018-2019 monthly average number of deaths; (2) 2015-2019 monthly average age-standardized mortality rates; (3) Seasonal Autoregressive Integrated Moving Average (SARIMA) models; (4) Generalized Estimating Equations (GEE) models. We analyzed deaths due to all-causes, circulatory diseases, cancer, and neurologic/mental disorders. Excess all-cause mortality estimates in 2020 across the four approaches were: +17.2% (2018-2019 average number of deaths), +9.5% (five-year average age-standardized rates), +15.2% (SARIMA), and +15.7% (GEE). For circulatory diseases (strong pre-pandemic decreasing trend), estimates were +7.1%, -4.4%, +8.4%, and +7.2%, respectively. Cancer mortality showed no relevant variations (ranging from -1.6% to -0.1%), except for the simple comparison of age-standardized mortality rates (-5.5%). The neurologic/mental disorders (with a pre-pandemic growing trend) estimated excess corresponded to +4.0%/+5.1% based on the first two approaches, while no major change could be detected based on the SARIMA and GEE models (-1.3%/+0.3%). The magnitude of excess mortality varied largely based on the methods applied to forecast mortality figures. The comparison with average age-standardized mortality rates in the previous five years diverged from the other approaches due to the lack of control over pre-existing trends. Differences across other methods were more limited, with GEE models probably representing the most versatile option.

Excess Total Mortality in Italy: An Update to February 2023 with Focus on Working Ages.

BACKGROUND: Italy had a persistent excess of total mortality up to July 2022. This study provides updated estimates of excess mortality in Italy until February 2023. METHODS: Mortality and population data from 2011 to 2019 were used to estimate the number of expected deaths during the pandemic. Expected deaths were obtained using over-dispersed Poisson regression models, fitted separately for men and women, including calendar year, age group, and a smoothed function of the day of the year as predictors. The excess deaths were then obtained by calculating the difference between observed and expected deaths and were computed at all ages and working ages (25-64 years). RESULTS: We estimated 26,647 excess deaths for all ages and 1248 for working ages from August to December 2022, resulting in a percent excess mortality of 10.2% and 4.7%, respectively. No excess mortality was detected in January and February 2023. CONCLUSIONS: Our study indicates substantial excess mortality beyond those directly attributed to COVID-19 during the BA.4 and BA.5 Omicron wave in the latter half of 2022. This excess could be attributed to additional factors, such as the heatwave during the summer of 2022 and the early onset of the influenza season.

Tracking the digital health gap in elderly: A study in Italian remote areas.

The Covid-19 pandemic has provided a major innovative thrust to public services regarding their digitization to continue providing an effective response to the population's needs and to reduce management costs. However, there has been a partial lack of those welfare policies that can provide an adequate response to the elderly segment of the population, which is most affected by the introduction of new technologies into the public sphere. This study analyses the digital gap in health in the elderly living in remote areas of Italy and investigates the use of digital devices for health purposes. It compares the use of digital solutions for health with people's common digital competencies and their willingness to use them. A descriptive analysis of the sample was constructed to verify the different responses of the elderly by age, gender, educational qualification, and geographic area. Furthermore, regression analyses have been conducted to test whether there is any dependent effect among the elderly's characteristics or geographic areas. The results highlight the existence of a potential digital health gap among the elderly in remote areas of Italy both due to infrastructural issues and the lack of digital skills. The latter are positively correlated with educational qualification, such that it is also possible to highlight differences between age groups analysed and shape future welfare policies to reduce digital inequality.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

Impact of tiered measures on social contact and mixing patterns of in Italy during the second wave of COVID-19.

BACKGROUND: Most countries around the world enforced non-pharmaceutical interventions against COVID-19. Italy was one of the first countries to be affected by the pandemic, imposing a hard lockdown, in the first epidemic wave. During the second wave, the country implemented progressively restrictive tiers at the regional level according to weekly epidemiological risk assessments. This paper quantifies the impact of these restrictions on contacts and on the reproduction number. METHODS: Representative (with respect to age, sex, and region of residence) longitudinal surveys of the Italian population were undertaken during the second epidemic wave. Epidemiologically relevant contact patterns were measured and compared with pre-pandemic levels and according to the level of interventions experienced by the participants. Contact matrices were used to quantify the reduction in the number of contacts by age group and contact setting. The reproduction number was estimated to evaluate the impact of restrictions on the spread of COVID-19. RESULTS: The comparison with the pre-pandemic baseline shows a significant decrease in the number of contacts, independently from the age group or contact settings. This decrease in the number of contacts significantly depends on the strictness of the non-pharmaceutical interventions. For all levels of strictness considered, the reduction in social mixing results in a reproduction number smaller than one. In particular, the impact of the restriction on the number of contacts decreases with the severity of the interventions. CONCLUSIONS: The progressive restriction tiers implemented in Italy reduced the reproduction number, with stricter interventions associated with higher reductions. Readily collected contact data can inform the implementation of mitigation measures at the national level in epidemic emergencies to come.

Pediatric asthma control during the COVID-19 pandemic.

BACKGROUND: The lockdown imposed by the COVID-19 pandemic resulted in a completely different style of life with possible effects on the attitude toward their disease in patients with chronic lung disease, such as asthma. The aim of our study was to investigate in asthmatic children the level of asthma control and the maintenance therapy used during the lockdown. METHODS: Among asthmatic children attending our clinic, we identified those who had been prescribed the same therapy in March-April 2019 and March-April 2020. The level of asthma control (GINA-score) and the maintenance therapy used during the lockdown (March-April 2020) were compared with those of March-April 2019. We separately analyzed a small group of children with severe asthma treated with Omalizumab during the lockdown. RESULTS: We enrolled 92 asthmatic children (67 males). Compared to 2019, in 2020 a higher proportion of children modified their maintenance therapy (38% vs. 15.2%, p < .001), with a significant increase in both the proportion of children who increased (p = .033) and in that of children who decreased their therapy (p = .026). The level of control resulted as significantly higher in 2020 (March p = .023; April p = .007). Also, the 13 children treated with Omalizumab showed a good level of control in 2020. CONCLUSIONS: In asthmatic children, the COVID-19 pandemic lockdown had a significant impact on their asthma control and on their attitude toward maintenance therapy.