COVID-19 in pregnancy may significantly affect fetal growth

Objective. Whilst most cases of COVID-19 in pregnancy evolve uneventfully, some others have a poor outcome, such as preterm birth and HDP. The effect of COVID-19 on fetal growth still has to be addressed and appears controversial. Our study aims to focus on fetal growth velocity across the trimesters in pregnancy affected with COVID-19. Materials and Methods. This is a multicentric prospective observational study on data from COVID-19 pregnancies referred to the centers of Careggi University Hospital and S. Stefano Hospital in Prato from 2020 to 2022, included in the local branch of ItOSS surveillance. Fetal growth was evaluated across the three trimesters of pregnancy by abdominal circumference (AC) and expected fetal weight (EFW). Both AC, and EFW plus birthweight were used to calculate growth velocity (Vannuccini et al., 2017). Results. Data from a cohort of 211 cases was collected. The majority (80%) of COVID-19 cases occurred in the third trimester. Of note, the percentage of gestational diabetes (12.3%) and preterm births (7.1%) was comparable to the general population. Mean birthweight was 3259 +/- 509 g. The percentage of cesarean sections was acceptable (13.7%). Concerning the velocity of growth, AC decreased from the second to third trimester to reach values < 10th centile in 24% of cases and < 5th percentile in 17% of cases, even in presence of 2% of hypertensive disorders (HDP). Fetal growth restriction according to Gordjin et al. (2015) was antenatally identified in 4.7% of cases. Fetal growth > 95th centile occurred in 5.7% of cases. At birth, the cumulative percentage of small for gestational age newborns defined as birth weight < 2500 g resulted 5.2%. A significant percentage of newborns required NICU assistance (7.8%). Conclusions. Regardless of the association and prevalence of preterm birth, SGA and HDP in pregnant women, fetal growth appears to be affected by COVID-19 with a higher incidence of impaired growth velocity compared to the general population.

Life threatening non-accidental burns, pandemic dependent telemedicine, and successful use of cultured Zurich Skin in a neonate - A case report

Life threatening burns of non-accidental origin in neonates are extremely rare. Their management represents a great challenge, particularly since necrosectomy of deep burns and grafting at this young age are technically very demanding. Thus, a strategic surgical master plan is mandatory to achieve rapid and definitive autologous coverage and avoidance of undue risks and iatrogenic burden for the fragile neonatal patient. We present the case of a four day-old neonate who sustained non-accidental deep burns involving 40 % of its total body surface area (TBSA) and the successful application of a laboratory grown, autologous dermo-epidermal skin analogue, termed Zurich Skin (also named denovoSkin), within a clinical trial sub-study. Due to COVID-19 pandemic restrictions, a telemedicine-based approach was installed and a total of 260 cm2 Zurich Skin were transplanted, video assisted, on a wound bed previously prepared with a dermal substitute, thereby covering 20 % TBSA. Take of Zurich Skin was excellent on the chest, good to moderate on the abdomen, and poor on other small areas, where we observed a prolonged healing. After maturation, Zurich Skin showed a close to natural skin coverage without need for further reconstructive surgery. This unique case delivers the proof of concept that Zurich Skin can be successfully applied in early life and even under most adverse medical and paramedical circumstances, provided a carefully crafted masterplan properly addressing the key issues can be executed by joint forces of committed partner institutions.Copyright © 2023 The Authors

Safety of Radiation exposure during pregnancy in COVID-19 affected women

Radiologic imaging in the evaluation of pregnant patients has significantly grown with the outbreak of the severe acute respiratory syndrome related to SARS-CoV-2 pandemic. Lung ultrasound is an emerging non-invasive bedside technique used to diag-nose interstitial lung syndrome through evaluation and quantitation of the number of B-lines, pleural irregularities and nodules or consolidations. In pregnant COVID-19 patients, lung ultrasound should be considered on ac-count of its various strengths, such as its being easily carried out bedside by trained sonographers for the monitoring of lung involvement in follow-ups, and its repeatability and affordability. However, pregnant patients could need chest radiography or computed tomo-graphic (CT) examinations for the diagnosis of pneumonia. Concerns and mis-conceptions about potential radiation-related risks for the embryo or fetus are still widespread among clinicians and can lead to excessive anxiety among pa-tients. Several well-recognized guidance documents were published in the last years as to the safety of a single-phase CT or an X-ray chest and related carcino-genic and teratogenic risk. This paper summarizes the safety of radiological examination for pneumonia in pregnant women affected by COVID 19, based on the estimated embryo-fetal radiation absorption per procedure (mGy).

Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children.

AIMS: Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR). METHODS AND RESULTS: We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (-17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (-17.2 ± 2.7 vs.-17.4 ± 4, P-value 0.71) and significantly improved at T2 (-19 ± 2.6% vs. -17.4 ± 4%, P-value 0.009). LV GLS was impaired (>-18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. CONCLUSION: Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.

POSB240 The Effects of COVID-19 Infection on Medication Adherence with Chronic Therapies in Italy: The Fail-to-Refill Project

Objectives: The study aimed to design and develop a monitoring system to assess the possible implications of the COVID-19 infection and the measures taken to limit its spreading on adherence to chronic therapies. Methods: Within the HEALTH-DB project and in collaboration with a pool of Local Healthcare Entities, a monitoring system called "fail-to-refill" was designed to evaluate the lack of adherence to chronic therapies in Italian clinical practice settings. Based on the date and dosage coverage of last prescription, all patients that should have refilled in the last month a prescription for chronic therapies are identified, and it is verified if they had the refill. The analysis was centred on two classes of chronic treatments, belonging to different distribution systems: lipid-lowering agents (distributed in community pharmacy) and biological therapies for chronic autoimmune conditions (dispensed by National Health System hospitals for outpatients use, ie direct distribution). The monthly analysis covered the no-COVID-19 period (01/2017-02/2020) and the COVID-19 period (03/2020-12/2020). Results: During the COVID-19 period, in May 2020, an increase (42%) of the fail-to-refill rate for lipid-lowering agents distributed in community pharmacies was observed, compared to the rate during the no-COVID-19 period (34% -35% during 2017-2019), while negligible changes were observed in the following months. Regarding the direct distribution, the fail-to-refill rate of biologics was higher during the COVID-19 period, 34% (May), 35% (June), and 37% (July) versus 26-30% (May 2017-2019), 28-29% (June 2017-2021), and 24-28% (July 2017-2019) of the no-COVID-19 period. Conclusions: During the COVID-19 pandemic, an increasing trend of failed refill to chronic therapies has been observed, especially among biologics, probably due to their dispensing system and the difficulty of accessing hospitals. The "fail-to-refill" monitoring system could support the Health Authorities to identify patients who do not correctly refill their prescriptions, thus optimizing the medication adherence and reducing negative clinical outcomes related to it.

POSA310 Artificial Intelligence Applied on Administrative Big Data to Predict the Severity of SARS-COV-2 Infection

Objectives: To estimate the prognostic factors underlying severity of Sars-Cov-2 infection using a machine learning approach. Methods: The analysis is based on administrative databases of Italian Entities. Patients who were hospitalized with COVID-19 diagnosis (ICD-9 078.89) after 1st January 2020 were included into the dataset together with 13 relevant features representing age, sex and clinical history of each patient. Each record was labelled as 0 (hospitalized patients) or 1 (patients in intensive care or deceased). KerasTuner was used to define the architecture of the Neural Network achieving good accuracy score. To identify prognostic factors underlying severity of Sars Cov-2 infection, feature’s importance was evaluated starting from a Random Forest Classifier. Results: The preliminary dataset built contains 10.448 records from 9.346 hospitalized patients. The selected neural network is made of 13 input nodes, each one representing a feature, 1024 nodes in the hidden layer, processing information that comes from the input layer, and 2 nodes in the output layer, each one representing a label to define patient’s condition. The neural network obtained was able to achieve 64% of accuracy on the testing set. The condition of approximately 2 out of 3 patients was correctly predicted just by analysing their features. The feature’s importance computed from the Random Forest Classifier indicated that patient’s age is the primary prognostic factor underlying severity of Sars Cov-2 infection. The combination of the other features slightly improved model’s performance. Conclusions: The preliminary analysis shows that age is a prognostic factor of fundamental importance in defining the severity of Sars Cov-2 infection. The model obtained could be used to predict disease progression in patients most at risk by analysing their information in the databases. The model will be further improved through a process of feature selection to increase its accuracy and to allow the identification of other prognostic factors.

Early echocardiographic and cardiac MRI findings in multisystem inflammatory syndrome in children (MIS-C)

Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is a known severe condition affecting children previously exposed to SARS-CoV-2. Cardiovascular manifestations in MIS-C are quite common and include myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. Severe cases can present even with cardiogenic shock. To date, little is known about the very early myocardial abnormalities in pediatric patients with MIS-C. The Speckle Tracking Echocardiography (STE) and cardiac MRI (cMRI) have shown to be potential candidate for identifying regional ventricular dysfunctions in early stages of inflammatory COVID-related conditions [1,2]. Objectives: To describe the early cardiac findings in patients with MIS-C, evaluated by two advanced cardiovascular imaging, STE and cMRI. Methods: Consecutive patients with MIS-C underwent standard transthoracic echocardiography (TTE), speckle-tracking echocardiography (STE) with analysis of left ventricle (LV) global longitudinal strain (GLS) and cardiac MRI (cMRI). Clinical and laboratory data, including markers of systemic inflammation, Troponin I (TnI) and Brain Natriuretic Peptide (BNP) were also collected at onset and during follow up. All patients received intravenous immunoglobulins (IVIGs), intravenous corticosteroids (methylprednisolone) and antiplatelet therapy (aspirin). The use of biological agents (Anakinra) was reserved to patients with severe or critical illness. The need for Intensive Care Unit (ICU) was based on clinical and hemodynamic status at presentation. Results: Twenty-three patients (13M, 10F), mean age 8.1±4years (range 5.4-15.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. The majority (78.2%) was caucasian. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular symptoms, as hypotension, thoracic pain or dysrhythmia, were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission and 3 required inotropic support. Short-term survival was 100%. All patients showed an hyperinflammatory state with elevated CRP, ESR, and D-Dimer. Tn- I was abnormal (>34 ng/L) in 15 patients (65.2%), BNP was significantly elevated in 20 (86.9%). Median time to STE evaluation was 8 days and to cMRI was 18 days since fever onset. Mean LVEF and RVEF were respectively 59±10% and 45±7%. Coronary dilation was observed in 6 (26.1%) patients. STE showed reduced mean LVGLS (-17±4.3%). LVEF on cMR was 60±13%, LGE with non-ischemic pattern was evident in 6/16 patients (37.5%) and pericardial effusion in 2 (12.5%). Conclusion: MIS-C can occur in a small but not negligible proportion of children previously affected by COVID-19 and affects the heart in a significant proportion of them. STE and cMRI were shown to be very sensitive tools to evaluate and monitor the early cardiac dysfunctions in patients with MIS-C. The elevation of myocardial necrosis markers, the myocardial injury confirmed by reduced LVGLS and presence of LGE on cMR in about a quarter of the patients support the pathogenetic hypothesis of a post-viral immuno-mediated myocarditis.

Impact of COVID-19 pandemic on maternal compliance to immunization for pertussis and influenza in pregnancy

INTRODUCTION Pertussis and influenza immunization in pregnancy is proven to be safe and effective in protecting mother and fetus. National Immunization Plan 2017-2019 recommends both as part of the free routine pregnancy care. Despite that national vaccination coverage among pregnant women is still negligible. The COVID-19 pandemic has globally challenged healthcare services including immunization. Our study evaluates if COVID-19 pandemic changed positively the attitude of pregnant women toward recommended vaccinations in pregnancy. METHODS We conducted a prospective observational study among women who delivered between June and August 2020 at the Maternity Unit of Prato. These patients experienced their first or second trimester during the 2019-2020 influenza seasonal epidemic (before COVID-19 pandemic) and their third trimester during COVID-19 pandemic and Italian lock-down. This study group represents a unique model to evaluate how the novel Coronavirus outbreak might have changed pregnant patients' attitude towards vaccination. Data were collected from a self-completed questionnaire about vaccination uptake, main motivations to be vaccinated or not, influence of COVID-19 on other immunizations. Data were analysed with descriptive statistics: frequencies, percentages, and mean with standard deviations were calculated for each question. RESULTS The survey focused on 195 women who returned complete questionnaire (on 520 patients eligible). Of these 70.2% were Italian, 11.8% Chinese, 3.6% Pakistani and 14.4% of other ethnicities. 8.7% reported vaccinated against influenza and 50.8% against pertussis. Of all these 6.7% received both vaccines during pregnancy. All women vaccinated against influenza were Italian, as well as the majority (87, 88%) of those who received the Tdap vaccine. For both vaccines the main motivation to be vaccinated was the vaccine to be recommended by an healthcare provider, as well as the main motivation not to be vaccinated was the lack of this recommendation. 26.1% women stated that lockdown measures reduced their access to vaccines. Of these women, 70.6% declared they would accept to be vaccinated if the vaccine was administered during a prenatal visit/hospitalization. 95.4% women declared they planned to have their newborns vaccinated following the national schedules for immunization in childhood. DISCUSSION In our sample in the pre-COVID-19 era less than 20% of the women were recommended to get the influenza vaccine, and only 9% were actually administered it. During the COVID-19 pandemic 60% were recommended to get Tdap vaccine, and more than 50% were actually administered it. The possible explanation of this difference in vaccine uptake in the same women might be a different sensitivity of women toward infectious disease complications and measures to prevent them. Our data suggest also that vaccinations are perceived as an essential care especially if recommended by obstetrical team and services. CONCLUSIONS Awareness of infectious disease threats have changed positively the attitude of pregnant women toward vaccination. While COVID-19 cases are steadily increasing globally, it is of upmost importance to reduce the burden of other preventable viral diseases. To avoid fear of contracting COVID-19 prevent immunization, as well as to minimize patient movements and therefore SARS-CoV-2 circulation, vaccination during routine prenatal care must be organized and encouraged.

Oncological patients’ perception of infection risks and level of acceptance of protective measures during SARS-CoV-2 pandemic

Background: The health emergency caused by the SarS-Cov-2 pandemic has a strong impact on oncological patients' (pts) life. The purpose of this study is to explore the emotional impact and pts' perception experienced who accessed to our Oncology section at University Hospital and Trust of Verona (Italy) regarding these rules. Method(s): An questionnaire was designed by our Psycho-Oncology service and administered to all pts accessing to our outpatient facilities during a 21-days period (April 9th - April 30th, 2020). Two main areas were investigated: i) organizational aspects and ii) awareness about infection risks, protective strategies, and new rules adopted (14 items, plus demographic data). Percentage of relevant answers to questionnaire items are reported with 95% confidence intervals (95% CI). Result(s): Among 241 respondents, fear of accessing hospital facilities and that chemotherapy treatment could increase the infection risk was reported to be quite high or high in 34% (95% CI: 29-41%) and 27% (95% CI: 21-33%), respectively. Awareness of disease-related risks of infection and strategies to reduce them was "very clear" or "fairly clear" [83% (95% CI: 78-88%) and 93% (95% CI: 90-96%), respectively]. Availability of medical personnel to be contacted while not in hospital was perceived as "very high". Almost all pts felt that organizational measures were clearly expressed (98%, 95% CI: 96-100%) and mainly obtained through the information received at the triage (73%, 95% CI: 67-79%). Overall acceptance of these measures was very high (>70%). Of note, the acceptance of phone-based follow-up and visits were perceived as "not very adequate" or "absolutely not adequate" by 17% (95% CI: 12-22 %) and 18% (95% CI: 13-23%) of respondents, respectively. Conclusion(s): Herein, we report among the first real-life experiences about oncological pts' perception of infection risks and their level of acceptance of protective measures during SarS-Cov-2 pandemic. A timely and thoughtful measures adoption, the coordinated efforts of all figures involved in cancer care and an effective communication strategy to share the necessary risks and sacrifices with pts/caregivers, can lead to effective protection of oncological pts. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2020

Organizational challenges and oncological activity volumes during the SARS-CoV-2 epidemic peak in Verona, Italy

Background: On February 23rd the first case of SARS-CoV-2 infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22 inpatient beds COVID unit and we had to reshape our organization and personnel to face the SARS-CoV-2 epidemic, while maintaining our oncological activity. Methods: We tracked down oncological activity from January 1st to March 31st, 2020, in relationship to the organizational changes implemented and in comparison to the same period of 2019. We also recorded cases of SARS-CoV-2 infections observed in oncology health professionals and hospital admissions of active oncology patients for SARS-CoV-2 infection. Results: Progressive restrictions in patients', visitors', and caregivers' access to the inpatient and outpatient facilities of the Oncology section and organizational changes were adopted early on during the epidemic peak. Since March 13th, segregated personnel teams were created, one dedicated to the COVID unit and a "clean" one dedicated to oncological patients, resulting in an overall 40% and 43% reduction in oncology-dedicated medical and nursing/auxiliary staff, respectively. As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations, and specialty visits in the period January-March 2020 was 8%, 6%, and 3%, respectively;based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. Patient's acceptance of adopted measures was very high (see abstract by Tregnago D). Overall, 8/85 (9%) health professionals tested positive for SARS-CoV-2 (no hospital admissions and no treatment required) and 7/525 (1.3%) active oncology patients were admitted for SARS-CoV-2 infection (of whom, 2 died of infection-related complications). Conclusions: A minimal (<10%) reduction in Oncology activity was registered during the peak of SARS-CoV-2 epidemic in Verona, Italy. Organizational and protective measures adopted appear to have contributed to keep infections in both health professionals and oncological patients to a minimum. Legal entity responsible for the study: University of Verona. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.