Differing kinetics of anti-spike protein IgGs and neutralizing antibodies against SARS-CoV-2 after Comirnaty (BNT162b2) immunization.

AIMS: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has had a serious worldwide impact on human health. On December 2020, an immunization campaign with a COVID-19 mRNA vaccine (Comirnaty-BNT162b2 Pfizer-BioNTech) was started in Italy, first targeting healthcare workers (HCWs). This study aims to investigate the antibodies that are response against SARS-CoV-2 vaccine. METHODS AND RESULTS: The kinetics and the persistence of both anti-S1/S2 IgGs and neutralizing antibodies (Nt-Abs) were investigated in 76 HCWs through a 4-month follow-up with multiple testing points starting at the first dose. Temporal analysis of SARS-CoV-2 Abs titre kinetics showed three different stages, with an initial slow growth in the anti-S1/S2 IgGs and Nt-Abs titres, corresponding to the first 4 weeks after the first dose of vaccine, followed by a second stage with peaks in titres, around 35 days after the first dose, and by a third stage (38 to 90-120 days after the first dose) showing a steady decrease in anti-S1/S2 IgGs while Nt-Abs are maintained at stable levels. Moreover, the levels of specific Nt-Abs to SARS-CoV-2 Spike protein are correlated to the anti-S1/S2 IgG titre (R-squared = 0.47; p < 0.001). CONCLUSIONS: The levels of specific Nt-Abs to SARS-CoV-2 Spike protein are correlated to the anti-S1/S2 IgG titre, although Nt-Abs could maintain a more stable titre over the time despite declining IgG Abs titre. SIGNIFICANCE AND IMPACT: This study highlights the kinetics and the persistence of Nt-Abs in HCWs vaccinated with Comirnaty (BNT162b2) Pfizer-BioNTech, and compared the Nt-Abs levels with anti-SARS-CoV-2 S1/S2 IgGs titres during a 4-month follow-up starting at the first dose of vaccine.

Clinical Severity in Different Waves of SARS-CoV-2 Infection in Sicily: A Model of Smith's "Law of Declining Virulence" from Real-World Data.

BACKGROUND: The COVID-19 epidemic had a rapid spread worldwide with a continuous and fast mutation of the virus, resulting in the emergence of several variants of concern (VOC). The aim of this study was to evaluate the severity of each VOC among SARS-CoV-2 infected subjects by investigating deaths, ICU admissions, intubations, and severe critical symptoms. METHODS: An ecological observational study was performed to evaluate mortality rates and clinical characteristics of 321,490 unvaccinated Sicilian SARS-CoV-2 cases observed from 2 March 2020 to 27 March 2022. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by multivariate logistic regression analysis evaluating factors determining a clinical worsening. RESULTS: Delta (adj-OR 3.00, 95% Cls 2.70-3.33) and wild-type (adj-OR 2.41, 95% Cls 2.2-2.62) variants had a higher risk than the Omicron strain for developing critical COVID-19 necessitating intubation and eventually undergoing death. Moreover, males appeared to be significantly more susceptible to developing the worst clinical outcome considered, as did older subjects. CONCLUSIONS: The present study provides evidence of factors implicated in the worsening of SARS-CoV-2-infection-related clinical outcomes. The study highlighted the different roles of VOC, in particular Delta and wild-type, and being male and elderly in the development of a worse clinical outcome.

School-age vaccination, school openings and Covid-19 diffusion.

This article investigates the relationship between school openings and Covid-19 diffusion when school-age vaccination becomes available. The analysis relies on a unique geo-referenced high frequency database on age of vaccination, Covid-19 cases and hospitalization indicators from the Italian region of Sicily. The study focuses on the change of Covid-19 diffusion after school opening in a homogeneous geographical territory (i.e., with the same control measures and surveillance systems, centrally coordinated by the Regional Government). The identification of causal effects derives from a comparison of the change in cases before and after school opening in the school year 2020/21, when vaccination was not available, and in 2021/22, when the vaccination campaign targeted individuals of age 12-19 and above 19. Results indicate that, while school opening determined an increase in the growth rate of Covid-19 cases in 2020/2021, this effect has been substantially reduced by school-age vaccination in 2021/2022. In particular, we find that an increase of approximately 10% in the vaccination rate of school-age population reduces the growth rate of Covid-19 cases after school opening by approximately 1%.

Increased Risk of Hospitalization for Pneumonia in Italian Adults from 2010 to 2019: Scientific Evidence for a Call to Action.

Background: Understanding trends in pneumonia-associated hospitalizations can help to quantify the burden of disease and identify risk conditions and at-risk populations. This study evaluated characteristics of hospitalizations due to pneumonia that occurred in Italy in a 10-year period from 2010 to 2019. Methods: All hospitalizations with a principal or secondary diagnosis of pneumonia over the 10-year period were included, which were identified by hospital discharges for all-cause pneumonia and pneumococcal pneumonia in the anonymized hospital discharge database of the Italian Health Ministry. Results: A total of 2,481,213 patients were hospitalized for pneumonia between 2010 and 2019; patients aged 75−86 years accounted for 30.1% of hospitalizations. Most hospitalizations (88.1%) had an unspecified pneumonia discharge code. In-hospital death was recorded in 13.0% of cases. The cumulative cost for pneumonia hospitalizations of the 10-year period were EUR 11,303,461,591. Over the observation period, the incidence rate for hospitalized all-cause pneumonia in any ages increased from 100 per 100,000 in 2010 to over 160 cases per 100,000 per year in 2019 (p < 0.001). Overall, there was a significant increase in annual percent changes in hospitalization rates (+3.47 per year), in-hospital death (+4.6% per year), and costs (+3.95% per year) over the 10-year period. Conclusions: Our analysis suggests that hospitalizations for pneumonia are increasing over time in almost all age groups, especially in the elderly. Given the substantial burden of pneumonia in terms of mortality, healthcare resources, and economic costs, greater public health efforts should thus be made to promote vaccinations against influenza and pneumococcus, particularly in high-risk groups.

Effectiveness of mRNA Vaccine Booster against SARS-CoV-2 Infection and COVID-19 in the Adult Population during the First Three Months of the Omicron Wave in Sicily.

BACKGROUND: In Italy, the administration of the COVID-19 vaccine booster dose started on 27 September 2021, supported by clinical trials corroborating its efficacy. Given the paucity of real-world effectiveness data, this study aims to estimate the vaccine effectiveness of the booster dose against SARS-CoV-2 infection, severe disease, and death in the adult Sicilian population. METHODS: This retrospective cohort study was carried out from 1 January to 31 March 2022 and included all residents in Sicily aged ≥ 18 years without previous SARS-CoV-2 infection and with a complete mRNA vaccine primary cycle. The cohort was split into two groups (booster and primary cycle) matched by age, gender, vaccine type, and month of completion of the primary vaccination cycle. RESULTS: 913,382 subjects were observed in the study: 456,690 (50%) were vaccinated with two doses and 456,692 (50%) with three doses. There were 43,299 cases of SARS-CoV-2 among the two-doses vaccinees (9.5%) and 10,262 (2.2%) among the three-doses counterpart. Vaccine effectiveness in the booster cohort was 76.5% and 74.4% against SARS-CoV-2 infection, 85.7% and 79.7% against severe disease, and 84.1% and 73.1% against intubation or death, for BNT162b2 and mRNA-1273, respectively. CONCLUSIONS: This study confirmed the remarkable efficacy profile of the SARS-CoV-2 vaccine booster dose against infection, severe disease, and death attributable to the virus. Overall, the results of this study provide important real-world data to support the continued roll-out of the COVID-19 booster dose and have the potential to inform public health policy and guide decisions on vaccination strategies in countries around the world.

Epidemiological Characteristics of COVID-19 Cases in Non-Italian Nationals in Sicily: Identifying Vulnerable Groups in the Context of the COVID-19 Pandemic in Sicily, Italy.

As in other parts of the world, undocumented migrants in Italy suffer worse health status due to their immigration enforcement situation and other vulnerabilities such as precarious illegal jobs, exploitation and abuse or barriers to higher education, with higher prevalence of chronic noncommunicable diseases. The COVID-19 pandemic, as other pandemics, has not affected everyone equally. The undocumented was one of the most affected groups with regard to hospitalization rates and mortality worldwide. Sicily is one of the gates of entrance to Europe for migrants and asylum seekers from Africa and Asia. Herein, we described the epidemiological characteristics of COVID-19 cases in Sicily to compare hospitalization rate and mortality between Italian nationals and foreigners. We extracted data from the integrated national surveillance system established by the Italian National Institute of Health (Istituto Superiore di Sanità, ISS) to collect information on all COVID-19 cases and deaths in Sicily. We found that the hospitalization rates were higher in undocumented foreigners, and they were most likely to present a more severe clinical outcome compared to Italian nationals. Inclusive public health policies should take this population group into consideration to achieve the Health for All goal.

Effectiveness of mRNA COVID-19 Vaccines in Adolescents Over 6 Months.

BACKGROUND AND OBJECTIVES: On June 4, 2021, Italy launched the coronavirus disease 2019 (COVID-19) vaccination of adolescents to slow down the COVID-19 spread. Although clinical trials have evaluated messenger ribonucleic acid (mRNA) vaccine effectiveness in adolescents, there is limited literature on its real-world effectiveness. Accordingly, this study aimed to estimate the effectiveness of mRNA COVID-19 vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild or severe COVID-19 in a cohort of Sicilian adolescents within a 6 month observation period. METHODS: A retrospective cohort study was conducted with adolescents aged 12 to 18 years, residents of Sicily, who were followed from July 15 to December 31, 2021. SARS-CoV-2 infections, mild and severe COVID-19, and COVID-19-related intubation or deaths during the study period were compared between subjects vaccinated with 2 doses of mRNA vaccines and unvaccinated individuals. The Cox regression analysis, adjusted for age and sex, was performed to compare the 2 groups. RESULTS: Overall, the study included a total at-risk population of 274 782 adolescents with 61.4% of them having completed the vaccination cycle by the end of the study. Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1043 × 10 000 vs 158.7 × 10 000 subjects), mild COVID-19 (27.7 × 10 000 vs 1.8 × 10 000 subjects) and severe COVID-19 (1.41 × 10 000 vs 0 subjects) compared with the vaccinated population. The estimated adjusted vaccine effectiveness against SARS-CoV-2 infection was 71.2%, reaching 92.1% and 97.9% against mild and severe COVID-19, respectively. CONCLUSIONS: This study provides rigorous evidence of mRNA COVID-19 vaccines' effectiveness in protecting adolescents from both SARS-CoV-2 infection and COVID-19.

Neutralizing Antibodies Response against SARS-CoV-2 Variants of Concern Elicited by Prior Infection or mRNA BNT162b2 Vaccination.

In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35-52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic.

Epidemiological Characteristics of COVID-19 Cases in Non-Italian Nationals in Sicily: Identifying Vulnerable Groups in the Context of the COVID-19 Pandemic in Sicily, Italy

As in other parts of the world, undocumented migrants in Italy suffer worse health status due to their immigration enforcement situation and other vulnerabilities such as precarious illegal jobs, exploitation and abuse or barriers to higher education, with higher prevalence of chronic noncommunicable diseases. The COVID-19 pandemic, as other pandemics, has not affected everyone equally. The undocumented was one of the most affected groups with regard to hospitalization rates and mortality worldwide. Sicily is one of the gates of entrance to Europe for migrants and asylum seekers from Africa and Asia. Herein, we described the epidemiological characteristics of COVID-19 cases in Sicily to compare hospitalization rate and mortality between Italian nationals and foreigners. We extracted data from the integrated national surveillance system established by the Italian National Institute of Health (Istituto Superiore di Sanità, ISS) to collect information on all COVID-19 cases and deaths in Sicily. We found that the hospitalization rates were higher in undocumented foreigners, and they were most likely to present a more severe clinical outcome compared to Italian nationals. Inclusive public health policies should take this population group into consideration to achieve the Health for All goal.

Wastewater-based epidemiology for early warning of SARS-COV-2 circulation: A pilot study conducted in Sicily, Italy.

There is increasing evidence of the use of wastewater-based epidemiology to integrate conventional monitoring assessing disease symptoms and signs of viruses in a specific territory. We present the results of SARS-CoV-2 environmental surveillance activity in wastewater samples collected between September 2020 and July 2021 in 9 wastewater treatment plants (WTPs) located in central and western Sicily, serving over 570,000 residents. The presence of SARS-CoV-2, determined in 206 wastewater samples using RT-qPCR assays, was correlated with the notified and geo-referenced cases on the areas served by the WTPs in the same study period. Overall, 51% of wastewater samples were positive. Samples were correlated with 33,807 SARS-CoV-2 cases, reported in 4 epidemic waves, with a cumulative prevalence of 5.9% among Sicilian residents. The results suggest that the daily prevalence of SARS-CoV-2 active cases was statistically significant and higher in areas with SARS-CoV-2 positive wastewater samples. According to these findings, the proposed method achieves a good sensitivity profile (78.3%) in areas with moderate or high viral circulation (≥133 cases/100,000 residents) and may represent a useful tool in the management of epidemics based on an environmental approach, although it is necessary to improve the accuracy of the process.

Effectiveness of mRNA COVID-19 Vaccination on SARS-CoV-2 Infection and COVID-19 in Sicily over an Eight-Month Period.

In order to reduce the spread of SARS-CoV-2 infection and the burden of disease, since 27 December 2020, Sicily has introduced a regional COVID-19 vaccination campaign. This study aimed at estimating the effectiveness of mRNA COVID-19 vaccines on SARS-CoV-2 infections and COVID-19. A retrospective cohort study was carried out on 3,966,976 Sicilian adults aged 18 years or more, who were followed-up from 1 January 2021 to 30 September 2021. The risk of SARS-CoV-2 infection, severe COVID-19, and COVID-19 death or intubation during the study period was compared among vaccinated with two mRNA doses and unvaccinated individuals. Cox regression, adjusted for age and sex, and a joint-point analysis on rate trends were performed. Overall, 2,469,320 (62.2%) subjects have been vaccinated and a total of 103,078 (2.6% of the entire population) SARS-CoV-2-positive subjects have been observed including 4693 (0.12%) severe COVID-19, 277 (0.01%) intubated, and 2649 (0.07%) deaths. After two months from vaccination, adjusted vaccine effectiveness was 81.3% against SARS-CoV-2 infection, 96.1% against severe COVID-19, and 93.4% against intubation/death. During the eight-month follow-up, statistically significant decreasing effectiveness trends were observed for all the evaluated outcomes (-4.76% per month against SARS-CoV-2 infection; -2.27% per month against severe COVID-19 and -2.26% per month against COVID-19 intubation/death). The study results confirm that mRNA COVID-19 vaccines have high real-world effectiveness, especially in the first months after vaccination. The vaccine effectiveness decreases over time and, even if the decrease is relatively small against severe outcomes, the increasing protection wane suggests the need for booster vaccination campaigns.

Adverse Reactions to Anti-SARS-CoV-2 Vaccine: A Prospective Cohort Study Based on an Active Surveillance System.

To date, Coronavirus disease (COVID-19) has caused high morbidity and mortality worldwide. To counteract the pandemic scenario, several vaccines against the etiological factor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed and tested. At the end of December 2020, BNT162b2 (Comirnaty, Pfizer-BioNTech) was the first and only authorized vaccine in Italy for selected categories, such as healthcare workers, fragile patients and people aged over 80 years old. To master our knowledge about BNT162b2 adverse reactions (ARs), an active surveillance system based on instant messaging was realized for voluntary participants who had been vaccinated at COVID-19 Vaccination Center of the Palermo University Hospital. Overall, 293 vaccinated persons were included in this study, which were more frequently healthcare workers (n = 207, 70.6% with a median age of 36 years, IQR = 29-55) followed by health professional students (n = 31, 10.6% with a median age of 27 years, IQR = 25-29), reporting 82.6% of at least one local or systemic AR. In details, the frequency of at least one local or systemic AR after the second dose of Comirnaty (n = 235, 80.2%) was statistically significant with higher value in comparison to the first one (n = 149, 50.9%; p < 0.001). However, local pain, swelling, joint pain and muscular pain after the second dose were the symptom causing a statistically significant working limitation. The youngest persons showed a higher risk to have either local or systemic ARs (aOR = 7.5, CI 95% = 2.9-18.9), while females had a higher risk of having systemic ARs (aOR = 1.8, CI 95% = 1.1-3.0). Despite the small sample examined, this active surveillance system by instant messaging seems to detect a higher ARs prevalence with respect to data obtained by the passive surveillance. Further studies could be required in order to optimize this clinical monitoring that could be considered an efficient and timely active surveillance.

Respiratory Syncytial Virus: New Challenges for Molecular Epidemiology Surveillance and Vaccination Strategy in Patients with ILI/SARI.

Several respiratory pathogens are responsible for influenza-like illness (ILI) and severe respiratory infections (SARI), among which human respiratory syncytial virus (hRSV) represents one of the most common aetiologies. We analysed the hRSV prevalence among subjects with ILI or SARI during the five influenza seasons before the emergence of SARS-CoV-2 epidemic in Sicily (Italy). Respiratory specimens from ILI outpatients and SARI inpatients were collected in the framework of the Italian Network for the Influenza Surveillance and molecularly tested for hRSV-A and hRSV-B. Overall, 8.1% of patients resulted positive for hRSV. Prevalence peaked in the age-groups <5 years old (range: 17.6-19.1%) and ≥50 years old (range: 4.8-5.1%). While the two subgroups co-circulated throughout the study period, hRSV-B was slightly predominant over hRSV-A, except for the season 2019-2020 when hRSV-A strongly prevailed (82.9%). In the community setting, the distribution of hRSV subgroups was balanced (47.8% vs. 49.7% for hRSV-A and hRSV-B, respectively), while most infections identified in the hospital setting were caused by hRSV-B (69.5%); also, this latter one was more represented among hRSV cases with underlying diseases, as well as among those who developed a respiratory complication. The molecular surveillance of hRSV infections may provide a valuable insight into the epidemiological features of ILI/SARI. Our findings add new evidence to the existing knowledge on viral aetiology of ILI and SARI in support of public health strategies and may help to define high-risk categories that could benefit from currently available and future vaccines.

Factors Affecting Hesitancy to mRNA and Viral Vector COVID-19 Vaccines among College Students in Italy.

Vaccine hesitancy (VH) may be significant in jeopardizing efforts to mass containment of COVID-19. A cross-sectional survey was carried out on a sample of 2667 Italian college students, before the COVID-19 vaccines became available for this age group (from 7 May to 31 May 2021). An online survey was created to obtain information about socio-demographic, health-related, and psychological factors linked to mRNA and viral vector COVID-19 vaccines. Statistically significant higher VH (30.4%) and vaccine resistance (12.2%) rates were found for viral vector than mRNA COVID-19 vaccines (7.2% and 1.0%, respectively; p < 0.001). Factors related to viral vector VH were partially different from those related to mRNA VH. Students with greater endorsement on conspiracy statements and negative attitudes toward the vaccine had higher odds of being vaccine-hesitant or -resistant. Students who had received a previous COVID-19 test and who scored higher on the agreeableness personality dimension had lower odds to be vaccine-hesitant or -resistant. The willingness to choose the vaccine was related to the viral vector but not to the mRNA VH. Taking into consideration the factors involved in vaccine hesitancy/resistance in college students could represent a key public health strategy to increase vaccine coverage and reduce viral spreading.

Socio-Demographic Factors Involved in a Low-Incidence Phase of SARS-CoV-2 Spread in Sicily, Italy.

BACKGROUND: The present study analysed SARS-CoV-2 cases observed in Sicily and investigated social determinants that could have an impact on the virus spread. METHODS: SARS-CoV-2 cases observed among Sicilian residents between the 1 February 2020 and 15 October 2020 have been included in the analyses. Age, sex, date of infection detection, residency, clinical outcomes, and exposure route have been evaluated. Each case has been linked to the census section of residency and its socio-demographic data. RESULTS: A total of 10,114 patients (202.3 cases per 100,000 residents; 95% CI = 198.4-206.2) were analysed: 45.4% were asymptomatic and 3.62% were deceased during follow-up. Asymptomatic or mild cases were more frequent among young groups. A multivariable analysis found a reduced risk of SARS-CoV-2 cases was found in census sections with higher male prevalence (adj-OR = 0.99, 95% CI = 0.99-0.99; p < 0.001) and presence of immigrants (adj-OR = 0.89, 95% CI 0.86-0.92; p < 0.001). Proportion of residents aged <15 years, residents with a university degree, residents with secondary education, extra-urban mobility, presence of home for rent, and presence of more than five homes per building were found to increase the risk of SARS-CoV-2 incidence. CONCLUSION: Routinely collected socio-demographic data can be predictors of SARS-CoV-2 risk infection and they may have a role in mapping high risk micro-areas for virus transmission.

PNPLA3 and TLL-1 Polymorphisms as Potential Predictors of Disease Severity in Patients With COVID-19.

Albeit the pathogenesis of COVID-19 remains unclear, host's genetic polymorphisms in genes involved in infection and reinfection, inflammation, or immune stimulation could play a role in determining the course and outcome. We studied in the early phase of pandemic consecutive patients (N = 383) with SARS-CoV-2 infection, whose subsequent clinical course was classified as mild or severe, the latter being characterized by admission to intensive therapy unit or death. Five host gene polymorphisms (MERTK rs4374383, PNPLA3 rs738409, TLL-1 rs17047200, IFNL3 rs1297860, and INFL4 rs368234815) were assessed by using whole nucleic acids extracted from nasopharyngeal swabs. Specific protease cleavage sites of TLL-1 on the SARS-CoV-2 Spike protein were predicted in silico. Male subjects and older patients were significantly at higher risk for a severe outcome (p = 0.02 and p < 0.001, respectively). By considering patients ≤65 years, after adjusting for potential confounding due to sex, an increased risk of severe outcome was found in subjects with the GG genotype of PNPLA3 (adj-OR: 4.69; 95% CI = 1.01-22.04) or TT genotype of TLL-1 (adj-OR=9.1; 95% CI = 1.45-57.3). In silico evaluation showed that TLL-1 is potentially involved in the Spike protein cleavage which is essential for viral binding and entry into the host cells using the host receptor angiotensin-converting enzyme 2 (ACE2). Subjects carrying a GG genotype in PNPLA3 gene might have a constitutive upregulation of the NLRP3 inflammasome and be more prone to tissue damage when infected by SARS-CoV-2. The TT genotype in TLL-1 gene might affect its protease activity on the SARS-CoV-2 Spike protein, enhancing the ability to infect or re-infect host's cells. The untoward effect of these variants on disease course is evident in younger patients due to the relative absence of comorbidities as determinants of prognosis. In the unresolved pathogenetic scenery of COVID-19, the identification of genetic variants associates with more prolonged course or with a severe outcome of infection would support the development of predictive tools useful to stratify subjects by risk class at presentation. Moreover, the individuation of key genes could contribute to a better understanding of the pathways involved in the pathogenesis, giving the basis for rational therapeutic approaches.

Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients.

COVID-19 is a current global threat, and the characterization of antibody response is vitally important to update vaccine development and strategies. In this study we assessed SARS-CoV-2 antibody concentrations in SARS-CoV-2 positive patients (N = 272) and subjects vaccinated with the BNT162b2 m-RNA COVID-19 vaccine (N = 1256). For each participant, socio-demographic data, COVID-19 vaccination records, serological analyses, and SARS-CoV-2 infection status were collected. IgG antibodies against S1/S2 antigens of SARS-CoV-2 were detected. Almost all vaccinated subjects (99.8%) showed a seropositivity to anti-SARS-COV-2 IgG and more than 80% of vaccinated subjects had IgG concentrations > 200 AU/mL. In a Tobit multivariable regression analysis, SARS-CoV-2 vaccination was statistically significantly associated with increased IgG concentrations (ß coef = 266.4; p < 0.001). A statistically significant reduction in SARS-CoV-2 IgG concentrations was found with older age (ß coef = -1.96 per year increase; p < 0.001), male sex (ß coef = -22.3; p < 0.001), and days after immunization (ß coef = -1.67 per day increase; p < 0.001). Our findings could support the vaccination campaigns confirming the high immunogenicity of the SARS-CoV-2 vaccine under investigation with respect to the natural infection. Further studies will be required for evaluating the role of age and days after immunization in the persistence of vaccine antibodies and protection from the disease.

Who Should Get COVID-19 Vaccine First? A Survey to Evaluate Hospital Workers' Opinion.

Prospective planning of COVID-19 vaccines allocation will be essential to maximize public health and societal benefits while preserving equity. Decisions about how to allocate limited supplies of vaccines need to be clear about the criteria used in setting priorities, with a specific commitment to transparency and communication. The aim of our study was to think through these competing demands, focusing on the opinion of healthcare workers (HCWs). The primary endpoint of the study was to assess the opinion of all the HCWs in a University based Italian Hospital about the fairest priority order to COVID 19 vaccines and to understand on which criteria the prioritization preferences of HCWs are implicitly based. The secondary endpoints were to assess whether HCWs approach differs from national guidelines and to assess the attitude of HCWs towards mandatory vaccination. An online survey accounting with multiple choice single answer questions and ranking questions was administered to all the HCWs of the University Hospital P. Giaccone of Palermo (Italy) and completed by a total of 465 participants. Almost all respondents confirmed the need for prioritization in COVID-19 vaccination for HCWs (n = 444; 95.5%), essential services and law enforcement (both n = 428; 92%). Clinically vulnerable individuals, HCWs and population over 65 years have been considered the first three groups to be involved in getting vaccination, being indicated as first position group by 26.5%, 32.5% and 21.9% of respondents, respectively. A large majority of respondents (85%) asked for a consistent, transparent and detailed order of priority at a national level. After adjusting for potential confounding due to sex and age, physicians have been found to be statistically significantly associated with the choice of mandatory vaccination (odds ratio (OR): 10.2; 95% confidence interval (CI) = 2.7-39.1) or with other strategies different from voluntary (OR = 7.2; 95% CI = 1.9-27.3). The broad consensus expressed by respondents towards mandatory vaccination for HCWs is extremely relevant at a time when vaccination hesitation is one of the biggest obstacles to achieving herd immunity. Data show a mismatch in the position attributed to long-term care residents compared to the position of absolute priority assigned by most of national distribution plans, impelling us to reflect on the issue of maximizing benefit from limited healthcare resources. Our findings clearly indicate a preference for COVID-19 frontline health professionals as the first tier of recipients, since they better meet all the criteria (higher risk, immediate system stability). As the guidelines are likely to directly affect a considerable number of citizens, our results call for policy interventions to inform people on the ethical rationale behind vaccine distribution decisions, to avoid resentment and feelings of unfairness.

SARS-CoV-2 Viral Load, IFNλ Polymorphisms and the Course of COVID-19: An Observational Study.

The course of SARS-CoV-2 infection ranges from asymptomatic to a multiorgan disease. In this observational study, we investigated SARS-CoV-2 infected subjects with defined outcomes, evaluating the relationship between viral load and single nucleotide polymorphisms of genes codifying for IFNλs (interferon). The study enrolled 381 patients with laboratory-confirmed SARS-CoV-2 infection. For each patient, a standardized form was filled including sociodemographic variables and clinical outcomes. The host's gene polymorphisms (IFNL3 rs1297860 C/T and INFL4 rs368234815 TT/ΔG) and RtReal-Time PCR cycle threshold (PCR Ct) value on SARS-CoV-2 were assessed on nasal, pharyngeal or nasopharyngeal swabs. Higher viral loads were found in patients aged > 74 years and homozygous mutant polymorphisms DG in IFNL4 (adj-OR = 1.16, 95% CI = 1.01-1.34 and adj-OR = 1.24, 95% CI = 1.09-1.40, respectively). After adjusting for age and sex, a statistically significantly lower risk of hospitalization was observed in subjects with higher RtReal-Time PCR cycle threshold values (adj-OR = 0.95, 95% CI = 0.91, 0.99; p = 0.028). Our data support the correlation between SARS-CoV-2 load and disease severity, and suggest that IFNλ polymorphisms could affect the ability of the host to modulate viral infection without a clear impact on the outcome of COVID-19.