EXPANDED NEWBORN SCREENING FOR INBORN ERRORS OF IMMUNITY: THE EXPERIENCE OF TUSCANY.

BACKGROUND: Inborn errors of immunity (IEIs) include 485 inherited disorders characterized by an increased susceptibility to life threatening infectious diseases, autoimmunity and malignant diseases with a high mortality rate in the first years of life. Severe Combined Immunodeficiency is the most severe of the IEIs and its detection should be a primary goal in a newborn screening (NBS) program. The term "actionable" has recently been used for all IEIs with outcomes that can be demonstrably improved through early specialized intervention. OBJECTIVE: to evaluate the results of the expanded NBS strategy for IEIs in Tuscany Region (Italy), based on TREC (T-cell Receptor Excision Circles), KREC (Kappa Recombining Excision Circles) and Tandem Mass-based assays. METHODS: This is a retrospective study collecting data from all infants born in Tuscany from October 10, 2018, to October 10, 2022. Tandem mass assay to identify Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency, together with TREC and KREC molecular analysis were conducted on dried blood spot (DBS) from the newborns' Guthrie Cards. A new DBS and evaluation by an immunologist were carried out when the results of the first test were outside the diagnostic cut-offs. RESULTS: 94,319 newborns were evaluated. Referral rates for TREC (0.031%) and KREC (0.074%) in this study are in line with the data available in literature. The results from the expanded NBS strategy revealed an incidence rate of 1/9,431 affected newborns. CONCLUSION: This work represents the first description of a sustainable and real-life based expanded NBS program for IEIs with a high diagnostic incidence facilitating prompt management of identified patients.

Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study.

The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence.

Four-Component Recombinant Protein-Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy.

Importance: Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD). Objective: To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy. Design, Setting, and Participants: This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022. Exposures: Routine 4CMenB vaccination, per regional vaccination programs. Main Outcomes and Measures: The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact. Results: The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose. Conclusions and Relevance: This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.

Relapse or worsening of chronic spontaneous urticaria during SARS-CoV-2 infection and vaccination in children: A telemedicine follow-up.

BACKGROUND: Chronic urticaria (CU), characterized by daily wheals and/or angioedema lasting more than 6 weeks, is a common skin disease. CU is classified as spontaneous or inducible. Because of Coronavirus Disease-19 (COVID-19) pandemic, face-to-face visits were reduced, and many centers started remote consultations to minimize hospital admissions and risk for viral diffusion. Telemedicine became a valuable tool for evaluating and monitoring patients with chronic diseases, such as CU. This study aims to evaluate the effectiveness of telemedicine as a means for the follow-up of patients with chronic spontaneous urticaria (CSU) during the COVID-19 pandemic. In particular, we collected data related to CSU evolution and treatment by remote consultation. Moreover, we specifically investigated the impact of SARS-CoV-2 infection or vaccination on CSU in relapsing or worsening of such a disease. METHODS: The electronic charts were reviewed for patients diagnosed with CSU, who were referred to the allergy unit of Meyer Children's Hospital, Florence. For each patient, a review of demographic characteristics, diagnostic workup, efficacy, and tolerability of the treatment was performed. Patients with a physical agent triggering CU were excluded from the study. Disease activity was monitored using the Urticaria Activity Score (UAS7). In addition, when the COVID-19 pandemic started, follow-up continued through telemedicine after an initial face-to-face visit when possible. Approximately 1 year after the diagnosis of CSU, patients were recontacted to investigate whether they had experienced a relapse or worsening of urticaria during a possible COVID-19 or immediately after receiving a COVID-19 vaccine. RESULTS: From January 2020 to March 2021, 84 cases of CSU were identified, with 71 (84.5%) of these being evaluated via televisit (remote consultation). During the remote follow-up period, 38/71 (53.5%) patients who were evaluated via televisit recovered completely from CSU, while 24 (33.8%) made therapy adjustments, and 9 (12.7%) had to discontinue follow-up through remote visits and return to face-to-face visits. In February 2022, we recontacted the 71 patients with CSU, and 50 (70.4%) of them answered by phone call interview. Four (19.2%) of the 26 patients who had COVID-19 showed CSU relapse, while 1 (3.8%) had a CSU worsening. Instead, 1 (3.8%) patient of the 26 who were vaccinated had a relapse of CSU, and 1 (3.8%) had a worsening of CSU, both after the first dose. CONCLUSION: Our data showed that telemedicine can be an effective tool for the follow-up of patients with CSU. Moreover, COVID-19, as well as COVID-19 vaccination, may trigger CSU relapse or worsening, but both are unspecific triggers, and urticaria shows a very short duration in most cases.

Relapse or worsening of chronic spontaneous urticaria during SARS-CoV-2 infection and vaccination in children: A telemedicine follow-up

Background Chronic urticaria (CU), characterized by daily wheals and/or angioedema lasting more than 6 weeks, is a common skin disease. CU is classified as spontaneous or inducible. Because of Coronavirus Disease-19 (COVID-19) pandemic, face-to-face visits were reduced, and many centers started remote consultations to minimize hospital admissions and risk for viral diffusion. Telemedicine became a valuable tool for evaluating and monitoring patients with chronic diseases, such as CU. This study aims to evaluate the effectiveness of telemedicine as a means for the follow-up of patients with chronic spontaneous urticaria (CSU) during the COVID-19 pandemic. In particular, we collected data related to CSU evolution and treatment by remote consultation. Moreover, we specifically investigated the impact of SARS-CoV-2 infection or vaccination on CSU in relapsing or worsening of such a disease. Methods The electronic charts were reviewed for patients diagnosed with CSU, who were referred to the allergy unit of Meyer Children’s Hospital, Florence. For each patient, a review of demographic characteristics, diagnostic workup, efficacy, and tolerability of the treatment was performed. Patients with a physical agent triggering CU were excluded from the study. Disease activity was monitored using the Urticaria Activity Score (UAS7). In addition, when the COVID-19 pandemic started, follow-up continued through telemedicine after an initial face-to-face visit when possible. Approximately 1 year after the diagnosis of CSU, patients were recontacted to investigate whether they had experienced a relapse or worsening of urticaria during a possible COVID-19 or immediately after receiving a COVID-19 vaccine. Results From January 2020 to March 2021, 84 cases of CSU were identified, with 71 (84.5%) of these being evaluated via televisit (remote consultation) (AU)

Severe pertussis disease in a paediatric population: The role of age, vaccination status and prematurity.

AIM: To estimate hospitalisation rate and investigate the role of age, prematurity and vaccination status in severe pertussis cases. METHODS: We retrospectively evaluated 200 children aged 0-14 years, admitted to the emergency rooms of Meyer Hospital of Florence and Pisa Hospital with a diagnosis of pertussis from 1 October 2010 to 31 January 2020. RESULTS: Children younger than 12 months were 63.0%. Preterm infants were 6.5%. The rate of hospitalisation was 49.0%. Among hospitalised cases, 80.6% were younger than 5 months. Overall, 62.0% were unvaccinated; this percentage increased among hospitalised (73.5%) and preterm subsamples (76.9%). Delays in pertussis vaccination were found in 57.7% of term infants and in 80.0% of preterms. Multivariable analysis confirmed the age under 2 months as the variable at higher risk for hospitalisation (OR 4.49, 95% CI 1.85-10.96, p < 0.001). Being fully vaccinated represented a significant protective factor (OR 0.12, 95% CI 0.04-0.35, p < 0.001). CONCLUSION: Older classes of age and a complete vaccination, in time with the recommended schedule, are both protective factors for hospitalisation in severe pertussis disease. The widespread vaccination delay frequently observed in preterm children may be the cause for their higher rate of hospitalisation.

Surveillance on Healthcare Workers During the First Wave of SARS-CoV-2 Pandemic in Italy: The Experience of a Tertiary Care Pediatric Hospital.

Healthcare workers (HCWs) play a central role in handling the ongoing coronavirus disease 2019 (COVID-19) pandemic. Monitoring HCWs, both symptomatic and asymptomatic, through screening programs, are critical to avoid the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the hospital environment to rapidly identify and isolate infected individuals and to allow their prompt return to work as soon as necessary. We aim to describe our healthcare surveillance experience (April 2-May 6, 2020) based on a combined screening consisting of real-time PCR (RT-PCR) on nasopharyngeal (NP) swabs and rapid serologic tests (RST) for SARS-CoV-2 in all HCWs of Meyer Children's University Hospital in Florence. Among the analyzed workers, 13/1690 (0.8%), all of them without clinical manifestations, was found positive for SARS-CoV-2 by using RT-PCR on NP swab: 8/1472 (0.5%) were found positive during the screening, 1/188 (0.5%) during contact with a positive individual (p > 0.05 vs. screening group), while 4/30 (13.3%) were found positive on the day of re-admission at work after an influenza-like-illness (p < 0.05). Concerning working areas, the majority of RT-PCR positivity (12/13) and serologic positivity (34/42) was found in non-COVID-19 dedicated areas (p > 0.05 vs. COVID-19 dedicated areas). No cases were registered among non-patients-facing workers (p = 0.04 vs. patient-facing group). Nurses and residents represented, respectively, the working role with the highest and lowest percentage of RT-PCR positivity. In conclusion, accurate surveillance is essential to reduce virus spread among HCWs, patients, and the community and to limit the shortage of skilled professionals. The implementation of the surveillance system through an efficient screening program was offered to all professionals, regardless of the presence of clinical manifestations and the level of working exposure risk, maybe wise and relevant.

How home anterior self-collected nasal swab simplifies SARS-CoV-2 testing: new surveillance horizons in public health and beyond.

The sample collection procedure for SARS-CoV-2 has a strong impact on diagnostic capability, contact tracing approach, ultimately affecting the infection containment performance. This study demonstrates that self-collected nasal-swab has shown to be a valid and well tolerated procedure to SARS-CoV-2 surveillance in a healthcare system. More significantly, no performance adequacy difference was detected in self-administered swabs between healthcare worker (HCW) and non-HCW which allows to speculate that this procedure could be successfully extended to the entire population for mass screening.

Independent Validation of the PAM50-Based Chemo-Endocrine Score (CES) in Hormone Receptor-Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2-Based Therapy.

PURPOSE: We do not yet have validated biomarkers to predict response and outcome within hormone receptor-positive/HER2-positive (HR+/HER2+) breast cancer. The PAM50-based chemo-endocrine score (CES) predicts chemo-endocrine sensitivity in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer. Here, we evaluate the relationship of CES with response and survival in HR+/HER2+ breast cancer. EXPERIMENTAL DESIGN: Intrinsic subtype and clinicopathologic data were obtained from seven studies in which patients were treated with HER2-targeted therapy either with endocrine therapy (ET) or with chemotherapy (CTX). CES was evaluated as a continuous variable and categorically from low to high scores [CES-C (chemo-sensitive), CES-U (uncertain), and CES-E (endocrine-sensitive)]. We first analyzed each dataset individually, and then all combined. Multivariable analyses were used to test CES association with pathologic complete response (pCR) and disease-free survival (DFS). RESULTS: A total of 457 patients were included (112 with ET and 345 with CTX). In the combined cohort, CES-C, CES-U, and CES-E were identified in 60%, 23%, and 17% of the patients, respectively. High CES (i.e., CES-E) was associated with a lower probability of achieving pCR independently of clinical characteristics, therapy, intrinsic subtype, and study (adjusted OR = 0.42; P = 0.016). A total of 295 patients were analyzed for DFS with a median follow-up of 66 months. High CES was also associated with better DFS (adjusted HR, 0.174; P = 0.003) independently of pCR, clinical characteristics and intrinsic subtype. In patients with residual disease, the adjusted DFS HR of CES was 0.160 (P = 0.012). CONCLUSIONS: In HER2+/HR+ breast cancer, CES is useful for predicting chemo-endocrine sensitivity and provides additional prognostication beyond intrinsic subtype and clinicopathologic characteristics.

Effectiveness and Impact of the 4CMenB Vaccine against Group B Meningococcal Disease in Two Italian Regions Using Different Vaccination Schedules: A Five-Year Retrospective Observational Study (2014-2018).

BACKGROUND: A few years after the introduction in Italy of a four-component anti-meningococcal B vaccine (4CMenB), we evaluated the effectiveness and impact of vaccination in two regions using different schedules (2, 4, 6, 12 months in Tuscany vs. 7, 9, 15 months in Veneto) through an observational retrospective study. METHODS: Vaccination started in 2014 in Tuscany and in 2015 in Veneto; the data collected referred to the period 2006-2018 for Tuscany and 2007-2018 for Veneto. Cases of invasive meningococcal disease due to N. Meningitidis B were identified by culture and/or real-time PCR. RESULTS: In Tuscany, pre-vaccine incidence was 1.96 (95% CL 1.52; 2.40) and dropped to 0.62 (95% CL 0.60; 0.64) in the post-4CMenB era. Evaluating only vaccinated children, post-4CMenB incidence was 0.12 (95% CL 0.08; 0.15). In Veneto pre-vaccine incidence was 1.94 (95% CL 1.92; 1.96) and dropped to 1.34 (95% CL 1.31; 1.38) in the post-4CMenB era. In the vaccinated population, MenB incidence was 0.53 (95% CL 0.50; 0.56). Vaccine effectiveness was 93.6% (95% CL 55.4; 99.1) in Tuscany and 91.0% (95% CL 59.9; 97.9) in Veneto, with mean vaccine coverages of 83.9% and 81.7%, respectively. The overall impact (evaluating both vaccinated and unvaccinated children) was 0.68 (95% CL 0.10; 0.89) in Tuscany and 0.31 (95% CL -0.56; 0.69) in Veneto; the total impact (evaluating only vaccinated children) was 0.94 (95% CL 0.56; 0.99) and 0.90 (95% CL 0.57; 0.97), respectively. The relative case reduction (RCR) was 65% in Tuscany and 31% in Veneto. Considering the vaccinated population, the RCR was equal to 91% and 80%, respectively. CONCLUSION: In conclusion, 4CMenB appears to have a very high effectiveness in Italy; the impact of vaccination appears greater where the immunization program is started early.