COVID-19 and precocious puberty: Does BMI play a role?

Background: Since COVID-19 the number of girls referred to pediatric endocrinologist for suspected precocious puberty (PP) and early puberty (EP) has increased. The aim of the study was to evaluate the incidence, the anthropometric, biochemical and radiological characteristics of PP during the COVID-19 pandemic, compared to previous years. Method(s): We retrospectively evaluated medical records of 464 females (F) referred to academic pediatric endocrinology center for suspected PP/EP from January 2016 to June 2021 (Group1: January 2016-March 2020, n=295;Group2: March 2020-June 2021, n=169). At first visit (V1) 289F had Idiopathic CPP (Group1 n=175;Group2 n=114) of which n=89 met the Rapidly Progressive Idiopathic CPP criteria (RP-ICPP;Group1 n=45;Group2 n=44) and n=200 for Slowly Progressive Idiopathic CPP (SP-ICPP;Group1 n=130;Group2 n=70). Additional n=44 of the SP-ICPP met the RP-ICPP criteria (Group1 n=27;Group2 n=17) at a second assessment (V2). Girls were classified by age at diagnosis (<6;6-6.99;7-7.99;>8 years). The total number of RP-ICPP was 133 (n=27 no-caucasians). Result(s): We found a higher incidence of RP-ICPP in Group 2 compared to Group1 (36% vs 24%, p<0.05, respectively);comparing the annual RP-ICPP incidences, 2021 showed the highest (p<0.05). RP-ICPP in Group1 and Group2 differed in age at diagnosis (7.96+/-0.71 vs 7.61+/-0.94;p<0.05) and in the time interval between thelarche and diagnosis (0.93+/-0.75 vs 0.74+/-0.64 yrs, p=0.05). We found a progressive increase in the number of girls Group2 in each age group<8 years (<6 years n=4 vs n=2;6-6,99 years n=7 vs n=4;7-7,99 years n=34 vs n=20), and a significant inverted proportion in girls >8 years (n=41 Group1 vs n=21 Group2, p<0.05). There were no differences between Group1 and Group2 for any anthropometric, biochemical and radiological parameters analyzed, except for blood glucose and cholesterol HDL levels (both highest in Group2 (p<0.05)). These data were confirmed in the total group and only in caucasian girls. By regression analyses we found that age at diagnosis was anticipated in Group2, regardless of BMI SDS. Analyzing the subgroup of patients with V2, BMI SDS V2-V1 was not different (-0.12+/-0.5 in Group1 vs 0.11+/-0.44 in Group2, p=0.17). Conclusion(s): During the Covid-19 pandemic the number of girls with suspected PP/EP resulted 1.79 fold increased, with a 1.5 time higher incidence of RC-ICPP. BMI doesn't seem to play a role, but further studies are needed to understand the etiology and primarily the role of metabolic parameters.

Incidence and severity of Coronavirus Disease 2019 (COVID-19) in children with primary and secondary adrenal insufficiency during the pandemic in Italy

Background: Adrenal insufficiency (AI) is a rare condition caused by an inadequate production of glucocorticoids. Preliminary data in adults suggest that AI could be associated with an increased susceptibility to infections;moreover, AI patients are at risk to develop a severe course of infectious diseases and to experience a life-threatening adrenal crisis. The aim of our study is to evaluate the severity and the outcome of COVID-19 in pediatric AI patients in comparison to subjects affected with other endocrinopathies not involving adrenal gland. Patients and Methods: This was a retrospective, multicenter study involving 11 Italian tertiary-centers of pediatric endocrinology. Data regarding symptoms, severity and duration of the disease, the need to increase the dose or receive parenteral administration of hydrocortisone and the outcome were collected through a telephone interview and review of patient's medical files. From March 2020 to October 2021, 80 children with a history of COVID-19 were collected: 49 subjects affected by AI (42 primary AI, 7 central AI) and 31 subjects as controls. Result(s): Mean age was comparable between patients and controls (11.4+/-4.4 years vs 10+/-3.5 years, respectively). The frequency of signs/symptoms during COVID-19 in AI patients was as follows: fever 68%, rhinorrhea 34%, headache 34%, sore-throat 30%, cough 28%, anosmia/ageusia 21%. Less common symptoms were characterized by arthralgia, abdominal pain, diarrhea and vomiting. The severity of infection was comparable between patients and controls: paucisymptomatic 40.8% vs 25.8%;mild 55.1% vs 61.3%;severe 4.1% vs 12.9%, respectively (Chi-square=0.19). Time between the first positive nasopharyngeal swab and the first negative one in patients vs controls was: <=15 days, 39% vs 56.6%;>15 days, 61% vs 43.3%, showing a tendency to longer infection in AI children, although this difference did not reach statistical significance (Chi-square=0.14). In 64% of AI patients the dose of hydrocortisone was increased during the infection and in 6.4% parenteral hydrocortisone was needed. 94% of AI subjects did not require hospitalization while only 6% were hospitalized with a complete recovery in 100% of cases. Within the entire cohort of AI subjects, 2 children (4%) experienced an adrenal crisis during infection. No fatal events occurred. Conclusion(s): Our data, suggest that children with AI adequately treated are not at increased risk of severe course of COVID-19. In comparison to controls, subjects with AI have a slightly longer duration of the disease, although this data need to be confirmed on larger sample of patients.

Predictive Role of Echocardiographic Pulmonary to Left Atrial Ratio for in-Hospital Death in Patients with Covid-19

Background and aims: Echocardiographic Pulmonary to Left Atrial ratio (ePLAR, tricuspid regurgitation Vmax/mitral E/e') represents an accurate and sensitive non-invasive tool to estimate trans-pulmonary pressure gradient, showing a sensitivity for pre-capillary pulmonary obstruction higher than traditional echocardiographic measures. The prognostic value of ePLAR in patients with coronavirus disease-2019 (COVID-19) remains unknown. We aimed to investigate the predictive role of ePLAR on mortality in COVID-19 patients. Method(s): One hundred consecutive patients admitted in two Italian institutions for COVID-19 undergoing early echocardiographic examination were included. ePLAR was determined from the maximum tricuspid regurgitation velocity at continuous wave Doppler (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). Main outcome measure was inhospital death. Result(s): Patients who died during hospitalization had a higher prevalence of tricuspid regurgitation, higher ePLAR and right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR >0.28 m/s showed increased in-hospital mortality compared to those having ePLAR <=0.28 m/s (27% vs 10.8%, p=0.05, Figure). A Cox model of multivariate analysis demonstrated that an ePLAR >0.28 m/s was independently associated with increased risk of death (HR 5.07, 95% CI 1.04-24.50, p=0.043), particularly among patients with increased pulmonary arterial pressure. Conclusion(s): A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially to guide strategies of diagnosis and treatment. (Figure Presented).

Hospital admissions and mortality for STEMI and NSTEMI during COVID-19 outbreak: a meta-analysis : Paolo Matteo Angeletti

Background During SARS-CoV-2 pandemic, various studies have shown a significant reduction of Emergency Department (ED) presentations for acute cardiac diseases requiring in-hospital management. The aim of our study was to quantify hospital admission and mortality, comparing pandemic period and pre-pandemic period in different countries. Methods We performed an updated meta-analysis of observational studies to quantify on a large basis the impact of the SARS-CoV-2 outbreak on patients admitted to the ED for STEMI and NSTEMI. The literature research was conducted on PubMed, EMBASE, Scopus, Science Direct, Web of Science and Cochrane database registry on 6 January 2022. We performed a random-effect model meta-analysis. Results A total of 61 studies were included: came from Italy, China, Germany, Israel, Turkey, France, Helvetic Confederation, India, Poland, Spain, US, UK, Albania, Austria, Egypt, Greece, Iran, Ireland, Japan, Pakistan, Portugal, Saudi Arabia and Canada. Hospital admissions for STEMI decreased in most country. The countries with the high levels of reduction were Italy (IRR = 0.68) and Germany (IRR = 0.69). Mortality rates for STEMI increased differently among countries analyzed: p = 0.003. The highest mortality rate was in Serbia (OR = 2.15), followed by Italy (OR = 1.97), Pakistan (OR = 1.69) and France (OR = 1.55). Among the High-Income countries, the highest mortality rate was in Italy (OR = 3.71), the highest among the Upper-Middle-Income was in Serbia (OR = 2.15) and the highest among Low- Middle-Income was in Pakistan (OR = 1.69). Regarding NSTEMI, hospital admissions showed that Italy had the lowest value for with IRR = 0.59. Among countries, the meta-regression subgroups analysis, showed statistical difference (p < 0.001). Conclusions Our meta-analysis may represent a robust snapshot that might help healthcare systems manage and assist an expected higher number of people coming to the hospitals for severe, post-acute cardiological issues in the future. Key messages • The study shows hospital admission and mortality, comparing pandemic period and pre-pandemic period in different countries. • Epidemiological data suggests that one-fourth to one-third of MI patients, in large areas of the globe, during the COVID-19 pandemic in 2020, remained at home and did not have access to ED.

Return towards normality in admissions for myocardial infarction after the lockdown removal for COVID-19 outbreak in Italy

BACKGROUND: Investigations demonstrated a decrease of admissions for myocardial infarction (MI) during the CoronaVirus Disease-19 (COVID-19) outbreak. No study has evaluated the time required to reverse this downward curve of MI admissions. METHODS: This is a retrospective analysis on patients (N = 2415) admitted to the Emergency Departments for acute MI in nine Italian centers. Primary endpoint was the incidence rates (IRs) of MI admissions in the post-lockdown COVID-19 period (case-period: from May 4 to July 12, 2020) vs. the following control periods: January 1-February 19, 2020 (pre-lockdown period);February 20-May 3, 2020 (intra-lockdown period);May 4-July 12, 2019 (inter-year non-COVID-19 period). RESULTS: IR of admissions for MI in the post-lockdown period was higher than the intra-lockdown period (IR ratio, IRR: 1.60, 95% CI 1.42-1.81;p = 0.0001), was lower than the pre-lockdown period (IRR: 0.86, 0.77-0.96;p = 0.009) and similar to the inter-year non-COVID-19 period (IRR: 0.96, 0.87-1.07;p = 0.47). Within the case period, the increase in MI admissions was more pronounced in earlier vs later weeks (IRR 1.19, 95% CI 1.02-1.38, p = 0.024) and, compared to the inter-year control period, was significant for non ST-segment elevation MI (IRR: 1.25, 95% CI 1.08-1.46, p = 0.004), but was not observed for ST-segment elevation MI (STEMI), where hospitalizations were reduced (IRR 0.76, 95% CI 0.65-0.88, p = 0.0001). CONCLUSIONS: Our study first indicates an increase in the number of admissions for MI after the removal of the national lockdown for COVID-19 in Italy. This increase was prevalent in the first weeks following the lockdown removal, but was under-represented in STEMI patients.

Impact of COVID-19 pandemic and infection on in hospital survival for patients presenting with acute coronary syndromes: A multicenter registry

INTRODUCTION: The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. METHODS: Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1-February 19, 2020) and previous-year control periods (February 20-May 3, 2019). ACS patients with Covid-19 were further compared with those without. RESULTS: Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively;p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%;p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p < 0.001) compared to patients without. Moreover, higher rates of cardiovascular death, cardiogenic shock and sustained ventricular tachycardia were found in Covid-19 patients. CONCLUSION: ACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported.