Binge drinking alcohol and circadian misalignment in night shift nurses is associated with decreased resiliency to COVID-19 infection

Background: Nurses and other first responders are at high risk of exposure to the SARS-CoV2 virus, and many have developed severe COVID-19 infection. A better understanding of the factors that increase the risk of infection after exposure to the virus could help to address this. Although several risk factors such as obesity, diabetes, and hypertension have been associated with an increased risk of infection, many first responders develop severe COVID-19 without established risk factors. As inflammation and cytokine storm are the primary mechanisms in severe COVID-19, other factors that promote an inflammatory state could increase the risk of COVID-19 in exposed individuals. Alcohol misuse and shift work with subsequent misaligned circadian rhythms are known to promote a pro-inflammatory state and thus could increase susceptibility to COVID-19. To test this hypothesis, we conducted a prospective, cross-sectional observational survey-based study in nurses using the American Nursing Association network. Method(s): We used validated structured questionnaires to assess alcohol consumption (the Alcohol Use Disorders Identification Test) and circadian typology or chronotype (the Munich Chronotype Questionnaire Shift -MCTQ-Shift). Result(s): By latent class analysis (LCA), high-risk features of alcohol misuse were associated with a later chronotype, and binge drinking was greater in night shift workers. The night shift was associated with more than double the odds of COVID-19 infection of the standard shift (OR 2.67, 95% CI: 1.18 to 6.07). Binge drinkers had twice the odds of COVID-19 infection of those with low-risk features by LCA (OR: 2.08, 95% CI: 0.75 to 5.79). Conclusion(s): Working night shifts or binge drinking may be risk factors for COVID-19 infection among nurses. Understanding the mechanisms underlying these risk factors could help to mitigate the impact of COVID-19 on our at-risk healthcare workforce.Copyright © 2023 The Authors. Alcohol: Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.

Variations in circadian rhythmicity and students' gender-related psychological conditions during the COVID-19 lockdown

In the face of the COVID-19 pandemic experienced around the world, new student lifestyles have had an impact on their daily behavior. The purpose of this study was to examine post-traumatic stress associated with the initial COVID-19 crisis in students (N = 280) with a mean age of 13 +/- 1.70 and to determine the relationship between their reported daily behaviors in terms of their gender. The study was conducted primarily in Casablanca and Marrakech, the two cities most affected by the pandemic at the time of the study in Morocco in May 2020. Our sample consists of 133 high school students and 147 middle school students, 83.6% of whom are females. Students were asked to answer questions based on an Activity Biorhythm Questionnaire, the Post-Traumatic Stress Scale (Weathers et al., 1993), the Hamilton Scale (Hamilton, 1960), the Worry Domains Questionnaire (Tallis, Eyzenck, Mathews, 1992), and the Visual Analog Scale of Moods (VASM) (Stern et al., 1997). The results obtained confirm that there is a significant relationship between the circadian rhythm of some variables and gender in some activities such as academic study (p < 0.05) and TV and Internet use (p < 0.05) and was highly significant for physical activity (p = 0.001), while others are not significant in relation to other schedules of the same variables or in relation to others. Likewise, for the psychological conditions, significant relationships with mood states and depressive tendencies were confirmed. In lockdown, the students' daily lives underwent changes in circadian rhythm and lifestyle. Therefore, it is necessary to treat their current psychological problems and avoid future complications. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

The Evolution of the Covid-19 Pandemic in Pediatric Patients with Sickle Cell Disease: From Alpha to Omicron

Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.

Potential Association of Remdesivir and Hyperkalemia: A Disproportionality Analysis in USFDA Adverse Event Reporting System Database

Background: Signal detection is one of the most advanced and promising techniques in the world of pharmacovigilance. Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) for patients with coronavirus disease 2019 (COVID-19). Its benefit- risk ratio is still being explored because data in the field are rather scant. On the other hand hyperkalemia is a potentially life-threatening electrolyte disorder. Severe hyperkalemia can occur suddenly and can cause life-threatening heart rhythm changes (arrhythmia) that cause a heart attack. Even mild hyperkalemia can cause heart related problems over time if not treated. Objective(s): To evaluate the potential association of Remdesivir with risk of Hyperkalemia by analyzing the spontaneous reports through disproportionality analysis. Method(s): Data were obtained from the public release of data in FAERS. Case/non-case method was adopted for the analysis of association between Remdesivir use and Hyperkalemia. The data-mining algorithm used for the analysis were Reporting Odds Ratio(ROR) and Proportional Reporting Ratio (PRR). A value of ROR-1.96SE>, PRR>=2 were considered as positive signal. Result(s): A total of 7 DE's associated with Remdesivir use and hyperkalemia were reported. The mean age of the patients of Remdesivir associated events was found to be 75 years [95% CI]. The reports by gender were distributed with a male to female ratio of 3:1, though gender was not revealed in 3 reports. The data mining algorithms exhibited positive signal for hyperkalemia (PRR: 2.349, ROR: 2.354) upon analysis as those were well above the pre-set threshold. Three case reports were identified which strengthened these findings and highlighted the importance of laboratory parameters for the early detection of hyperkalemia Conclusion(s): The current study found a potential risk of hyperkalemia with the use of Remdesivir and there is an urgent need to thoroughly investigate the same and take the necessary action to avoid or minimize the risk.Copyright © 2023

Onsite versus home-office: differences in sleep patterns according to workplace.

Background and objective: This study aimed to evaluate the sleep patterns of students and employees working onsite versus those working from home during the COVID-19 pandemic using actigraphy. Methods: A total of 75 students/employees (onsite: N = 40, home-office: N = 35; age range: 19-56 years; 32% male; 42.7% students, 49.3% employees) were studied between December 2020 and January 2022 using actigraphy, a sleep diary, and an online questionnaire assessing sociodemographics and morningness-eveningness. Independent-sample t-tests, paired-sample tests, and a multivariate general linear model adjusting for age (fixed factors: sex and work environment) were applied. Results: Overall, onsite workers had significantly earlier rise times (7:05 [SD: 1:11] versus 7:44 [1:08] hours) and midpoints of sleep (2:57 [0:58] versus 3:33 [0:58] hours) on weekdays compared to home-office workers. Sleep efficiency, sleep duration, variability of sleep timing, and social jetlag did not differ between the groups. Discussion: Home-office workers showed a delay in sleep timing that did not affect any other sleep parameters such as sleep efficiency or nighttime sleep duration. The work environment had only marginal impact on sleep patterns and thus sleep health in this sample. Sleep timing variability did not differ between groups. Supplementary Information: The online version of this article (10.1007/s11818-023-00408-5) contains supplementary material 1 and 2, which is available to authorized users.

Delayed sleep-wake phase disorder and its related sleep behaviors in the young generation.

Delayed sleep-wake phase disorder (DSWPD) is a sleep disorder in which the habitual sleep-wake timing is delayed, resulting in difficulty in falling asleep and waking up at the desired time. Patients with DSWPD frequently experience fatigue, impaired concentration, sleep deprivation during weekdays, and problems of absenteeism, which may be further complicated by depressive symptoms. DSWPD is typically prevalent during adolescence and young adulthood. Although there are no studies comparing internationally, the prevalence of DSWPD is estimated to be approximately 3% with little racial differences between Caucasians and Asians. The presence of this disorder is associated with various physiological, genetic and psychological as well as behavioral factors. Furthermore, social factors are also involved in the mechanism of DSWPD. Recently, delayed sleep phase and prolonged sleep duration in the young generation have been reported during the period of COVID-19 pandemic-related behavioral restrictions. This phenomenon raises a concern about the risk of a mismatch between their sleep-wake phase and social life that may lead to the development of DSWPD after the removal of these restrictions. Although the typical feature of DSWPD is a delay in circadian rhythms, individuals with DSWPD without having misalignment of objectively measured circadian rhythm markers account for approximately 40% of the cases, wherein the psychological and behavioral characteristics of young people, such as truancy and academic or social troubles, are largely involved in the mechanism of this disorder. Recent studies have shown that DSWPD is frequently comorbid with psychiatric disorders, particularly mood and neurodevelopmental disorders, both of which have a bidirectional association with the pathophysiology of DSWPD. Additionally, patients with DSWPD have a strong tendency toward neuroticism and anxiety, which may result in the aggravation of insomnia symptoms. Therefore, future studies should address the effectiveness of cognitive-behavioral approaches in addition to chronobiological approaches in the treatment of DSWPD.

Corrigendum: The impact of circadian rhythm on Bacillus Calmette-Guérin vaccination effects on SARS-CoV-2 infections.

[This corrects the article DOI: 10.3389/fimmu.2023.980711.].

Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients.

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to the HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. Ten patients (2.4%) developed QTc prolongation > 60 ms, and none had QTc > 500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are applied.

Has COVID-19 changed the spectrum of arrhythmias and the incidence of sudden cardiac death?

Arrhythmic manifestations of COVID-19 include atrial arrhythmias such as atrial fibrillation or atrial flutter, sinus node dysfunction, atrioventricular conduction abnormalities, ventricular tachyarrhythmias, sudden cardiac arrest, and cardiovascular dysautonomias including the so-called long COVID syndrome. Various pathophysiological mechanisms have been implicated, such as direct viral invasion, hypoxemia, local and systemic inflammation, changes in ion channel physiology, immune activation, and autonomic dysregulation. The development of atrial or ventricular arrhythmias in hospitalized COVID-19 patients has been shown to portend a higher risk of in-hospital death. Management of these arrhythmias should be based on published evidence-based guidelines, with special consideration of the acuity of COVID-19 infection, concomitant use of antimicrobial and anti-inflammatory drugs, and the transient nature of some rhythm disorders. In view of new SARS-CoV­2 variants that may evolve, the development and use of newer antiviral and immunomodulator drugs, and the increasing adoption of vaccination, clinicians must remain vigilant for other arrhythmic manifestations that may occur in association with this novel but potentially deadly disease.

Cuban Vaccines Abdala and Mambisa against Covid-19

Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023

Ahead of the Curve - Experience from the Uk's First Dedicated Specialist Crm Clinic for Achd Patients

Background: The population of Adults with Congenital Heart Disease (ACHD) is expanding. A significant number will require Cardiac Rhythm Management (CRM) devices. In current UK practice, these patients are routinely seen in non-specialist CRM clinics and little is published regarding best-practice CRM programming and management in the ACHD population. Objective(s): Our objective was to establish a new model of patient-centred/-specific care delivered by specialist CRM physiologists, supported by an EP consultant (with a special interest in ACHD) in a dedicated clinic. We hoped to set new standards of care and patient experience, and improve efficiency and outcomes. Method(s): Data was collected from the electronic record system and CRM device database. A control group of non-ACHD patients was selected at random at our institution over the same period (2018-2022). Result(s): The clinic population n = 468 had a sex ratio of 0.92 (M:F) and mean age of 44 years (range 16 - 86). Mean time since primary implant was 9 years. All device types were represented: loop recorder (52), pacemaker (262), cardioverter defibrillator (116) and cardiac resynchronisation therapy devices (38). The underlying ACHD condition was: simple 46%, moderate 28% and complex 26%. Outcomes of appointments (n = 1,234) are shown vs controls (n = 126) (figure 1). Appointment and patient numbers rose year-on-year (100 to 226 patients, 281 to 367 appointments). There was a lower incidence of 'no review / reprogramming ' in ACHD CRM clinic appointments compared to the non-ACHD population, as well as a higher incidence of programming changes, however the trend over time within the ACHD group showed an increase in 'no review / reprogramming' and a decrease in reviews / reprogramming events. In contrast, non-ACHD patients had an increase in medical reviews and reprogramming required between 2018/19 and 2021/22. This is likely due to the COVID pandemic and deferred time to appointments and review. Conclusion(s): Our data demonstrate that the ACHD CRM population require additional input from the medical and scientist teams when compared to non-ACHD patients, however over time there has been a reduction in major programming/review and a commensurate increase in minor programming/discussion and no review. A reverse trend was observed in the non-ACHD patients pre- and post- COVID. These data support the proposal that specialised clinics provide the optimal management ACHD CRM clinics and should be delivered by dedicated practitioners. [Formula presented]Copyright © 2023

Comprehensive Program of Neurotherapy for a Visual Artist with Post-Covid-19 Syndrome Following Sars-Cov-2 Infection and Severe Course of Covid-19 Treated in Long-Term Pharmacologically Induced Coma

Background: Case study: Conclusion(s): The purpose of the study was twofold: (1) to present post-COVID-19 syndrome, which involves a variety of ongoing neurological, neuropsychiatric, neurocognitive, emotional and behavioral disorders resulting from SARS-CoV-2 infection followed by a severe course of COVID-19 treated in long term pharmacologically induced coma in a visual artist, which impacted on her artwork;(2) to present QEEG/ERP results and neuropsychological testing results in the evaluation of the effectiveness of a comprehensive neurotherapy program, with individualized EEG-Neurofeedback, and art-therapy in the reduction of post-COVID-19 syndrome in this artist. Ms. G., 42, a visual artist, portraitist, with good health, became ill in May 2022. Allegedly flu symptoms appeared first. After a few days, shortness of breath joined in. The PCR test for SARS-CoV-2 was positive. The patient was hospitalized, referred to the ICU, put on a respirator and treated over 11days of a pharmacologically induced coma. Two months after leaving hospital the patient developed post-COVID-19 syndrome. She was diagnosed by an interdisciplinary team: a neurologist, neuropsychiatrist and neuropsychologist. A PET scan of her brain revealed extensive changes involving a loss of metabolism in various brain areas. The presence of complex post-COVID, neurological, neuropsychiatric, neurocognitive, emotional and behavioral disorders was found and a neuropsychiatrist suggested a diagnosis of post-COVID schizophrenia. She was refered to the Reintegration and Training Center of the Polish Neuropsychological Society.We tested the working hypothesis as to the presence of schizophrenia and there was no reduction in the difference of ERPs waves under GO/NOGO task conditions, like in the reference group with schizophrenia (see also Pachalska, Kaczmarek and Kropotov 2021). The absence of a functional neuromarker for schizophrenia allowed us to exclude this diagnosis and to propose a new disease entity, that being post-COVID-19 syndrome. She received a comprehensive two-component program of neurotherapy: (1) program A consisting in goal-oriented neuropsychological rehabilitation, including art therapy (see also: Pachalska 2008;2022b), and (2) program B, based on the most commonly used form of EEG-Neurofeedback: frequency/ power EEG-Neurofeedback, using 2 bipolar surface electrodes, with the protocols written for her specific needs (see also Thompson & Thompson 2012;Kropotov 2016). The comprehensive neurotherapy program lasted 10 weeks, EEG Neurofeedback and art therapy classes were conducted 3 times a week for 45 minutes each. We found that after the completion of the comprehensive neurotherapy program there was a statistically significant reduction in high beta activity compared to the normative HBI database, which is associated with a reduction of anxiety. Also, we observed the improvement of neurocognitive functioning in neuropsychological testing (a significant reduction of anxiety and a noticeable improvement in neurocognitive functions). It should be stressed that the artist was happy that she had regained the ability to create, and even sells her artwork, although her style of painting had changed. Almost all the neurological, psychiatric, neurocognitive, emotional and behavioral disturbances, were reduced in their severity. The artist showed marked improvement and was able to return to painting. The artwork she produced after her illness is in high demand with art collectors. It can be also helpful in the reintegration of the Self System, and the improvement in her quality of life. Human Brain Index (HBI) methodology might be very useful in diagnosing and developing therapies for patients with post-COVID-19 syndrome.Copyright © 2023, MEDSPORTPRESS Publishing House. All rights reserved.

Covid-19 Vaccine Associated Acute Myocarditis

Case Presentation: A 19 year old male presented with sudden onset chest pain radiating to back. He was a smoker and denied using cocaine since his last hospitalization for cocaine-induced myocardial infarction 2 years ago. UDS was negative. EKG showed normal sinus rhythm with no ST-T wave changes. Initial troponin was 0.850. Potassium levels were low at 2.9 mmol/L but other labs were normal. Chest CT angiography ruled out aortic dissection. He was started on heparin drip. Stat Echocardiogram showed LVEF of 55-60% with no wall motion abnormalities. Repeat potassium levels normalized after replacement, however, his troponins were trending up from 3.9 and 11.5. He continued to complain of severe chest pain, so underwent cardiac catheterization which showed normal coronary arteries and LVEF 55-60%. Heparin drip was discontinued and NSAIDs and colchicine were started. Cardiac MRI (see Figure) was done that showed patchy mid-wall and epicardial delayed gadolinium enhancement involving the basal inferolateral wall, with mild hyperintense signal on the triple IR sequence, suggestive of myocarditis. On further probing, he reported receiving a second dose of Moderna COVID vaccine 3 days prior to presentation. Discussion(s): In December 2019, a novel RNA virus causing COVID-19 infection was reported, which quickly reached a pandemic level. COVID-19 vaccines were granted emergency use authorization by FDA. With millions of people receiving COVID-19 vaccinations worldwide, rare adverse effects are now being reported. The benefits of vaccination undoubtedly outweigh any minor side effects. However major adverse effects like this are potentially fatal. This case report warrants further investigation into the association of myocarditis with COVID-19 vaccinations and further recommendations regarding vaccination in younger adults.

Atrio-Ventricular Conduction Abnormalities in Multisystem Inflammatory Syndrome in Children

Purpose of study Since mid-April 2020 in Europe and North America, clusters of pediatric cases with a newly described severe systemic inflammatory response with shock have appeared. Patients had persistent fevers >38.5 C, hypotension, features of myocardial dysfunction, coagulopathy, gastrointestinal symptoms, rash, and elevated inflammatory markers without other causes of infection. The World Health Organization, Centers for Disease Control, and Royal College of Paediatrics associated these symptoms with SARS-CoV-2 as multisystem inflammatory syndrome in children (MIS-C). Cardiac manifestations include coronary artery aneurysms, left ventricular systolic dysfunction evidenced by elevation of troponin-T (TnT) and pro-B-type naturietic peptide (proBNP), and electrocardiogram (ECG) abnormalities. We report the clinical course of three children with MIS-C while focusing on the unique atrioventricular (AV) conduction abnormalities. Case #1:19-year-old previously healthy Hispanic male presented with abdominal pain, fever, and non-bloody diarrhea for three days. He was febrile and hypotensive (80/47 mmHg) requiring fluid resuscitation. Symptoms, lab findings, and a positive COVID-19 antibody test were consistent with MIS-C. Methylprednisolone, intravenous immunoglobulin (IVIG), and enoxaparin were started. He required epinephrine for shock and high flow nasal cannula for respiratory distress. Initial echocardiogram demonstrated a left ventricular ejection fraction (LVEF) of 40% with normal appearing coronaries. Troponin and proBNP were 0.41 ng/mL and proBNP 15,301 pg/mL respectively. ECG showed an incomplete right bundle branch block. He eventually became bradycardic to the 30s-50s and cardiac tracing revealed a complete AV block (figure 1a). Isoproterenol, a B1 receptor agonist, supported the severe bradycardia until the patient progressed to a type 2 second degree AV block (figure 1b). A second dose of IVIG was administered improving the rhythm to a type 1 second degree AV block. An IL-6 inhibitor, tocilizumab was given as the rhythm would not improve, and the patient soon converted to a first-degree AV block. Cardiac magnetic resonance imaging showed septal predominant left ventricular hypertrophy and subepicardial enhancement along the basal inferior/anteroseptal walls typical for myocarditis. Case #2: 9-year-old previously healthy Hispanic male presented after three days of daily fevers, headaches, myalgias, diffuse abdominal pain, and ageusia. He was febrile, tachycardic, and hypotensive (68/39 mmHg). Hypotension of 50s/20s mmHg required 3 normal saline boluses of 20 ml/kg and initiation of an epinephrine drip. Severe hypoxia required endotracheal intubation. After the MIS-C diagnosis was made, he was treated with IVIG, mehtylprednisolone, enoxaparin, aspirin, and ceftriaxone. Due to elevated inflammatory markers by day 4 and patient's illness severity, a 7-day course of anakinra was initiated. Initial echocardiogram showed mild tricuspid and mitral regurgitation with a LVEF of 35-40%. Despite anti-inflammatory therapy, troponin and proBNP were 0.33 ng/mL and BNP of 25,335 pg/mL. A second echocardiogram confirmed poor function so milrinone was started. Only, after two doses of anakinra, LVEF soon normalized. Despite that, he progressively became bradycardic to the 50's. QTc was prolonged to 545 ms and worsened to a max of 592 ms. The aforementioned therapies were continued, and the bradycardia and QTc improved to 405 ms. Patient #3: 9-year-old African American male presented with four days of right sided abdominal pain, constipation, and non-bilious non-bloody emesis. He had a negative COVID test and unremarkable ultrasound of the appendix days prior. His history, elevated inflammatory markers, and positive COVID- 19 antibody were indicative of MIS-C. He was started on the appropriate medication regimen. Initial ECG showed sinus rhythm with normal intervals and echocardiogram was unremarkable. Repeat imaging by day three showed a decreased LVEF of 50%. ECG had since changed to a right bundle branch block. Anakinra as started and steroid dosing was increased. By day 5, he became bradycardic to the 50s and progressed to a junctional cardiac rhythm. Cardiac function normalized by day 7, and anakinra was subsequently stopped. Thereafter, heart rates ranged from 38-48 bpm requiring transfer to the pediatric cardiac intensive care unit for better monitoring and potential isoproterenol infusion. He remained well perfused, with continued medical management, heart rates improved. Methods used Retrospective Chart Review. Summary of results Non-specific T-wave, ST segment changes, and premature atrial or ventricular beats are the most often noted ECG anomalies. All patients initially had normal ECGs but developed bradycardia followed by either PR prolongation or QTc elongation. Two had mild LVEF dysfunction prior to developing third degree heart block and/or a junctional escape rhythm;one had moderate LVEF dysfunction that normalized before developing a prolonged QTc. Inflammatory and cardiac markers along with coagulation factors were the highest early in disease course, peak BNP occurred at approximately hospital day 3-4, and patient's typically had their lowest LVEF at day 5-6. Initial ECGs were benign with PR intervals below 200 milliseconds (ms). Collectively the length of time from initial symptom presentation till when ECG abnormalities began tended to be at day 8-9. Patients similarly developed increased QTc intervals later in the hospitalization. When comparing with the CRP and BNP trends, it appeared that the ECG changes (including PR and QTc elongation) occurred after the initial hyperinflammatory response. Conclusions Although the mechanism for COVID-19 induced heart block continues to be studied, it is suspected to be secondary to inflammation and edema of the conduction tissue. Insufficiency of the coronary arterial supply to the AV node and rest of the conduction system also seems to play a role. Although our patients had normal ECG findings, two developed bundle branch blocks prior to more complex rhythms near the peak of inflammatory marker values. Based on the premise that MIS-C is a hyperinflammatory response likely affecting conduction tissue, our group was treated with different regimens of IVIG, steroids, anakinra, and/or tocilizumab. Anakinra, being an IL-1 inhibitor, has been reported to dampen inflammation in viral myocarditis and tocilizumab has improved LVEF in rheumatoid arthritis patients. Based on our small case series, patient's with MISC can have AV nodal conduction abnormalities. The usual cocktail of IVIG and steroids helps;however, when there are more serious cases of cardiac inflammation, adjuvant immunosuppresants like anakinra and toculizumab can be beneficial. (Figure Presented).

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID.

BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity. METHODS: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in a post-COVID cohort, compared those with or without symptoms, and correlated findings with previously measured biomarkers. RESULTS: Sixty participants (median age 53, 42% female, 87% non-hospitalized) were studied at median 17.6 months following SARS-CoV-2 infection. On CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted) compared to 3/19 (16%) without symptoms (p = 0.02). Adjusted peak VO2 was 5.2 ml/kg/min lower (95%CI 2.1-8.3; p = 0.001) or 16.9% lower percent predicted (95%CI 4.3-29.6; p = 0.02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2 more than 1 year later. Late-gadolinium enhancement on CMR and arrhythmias were absent. CONCLUSIONS: Cardiopulmonary symptoms >1 year following COVID-19 were associated with reduced exercise capacity, which was associated with elevated inflammatory markers early in PASC. Chronotropic incompetence may explain exercise intolerance among some with cardiopulmonary Long COVID.

Pseudo-V1 ECG lead recording with quality smartwatches and medical interpretation may be necessary for timely and accurate remote detection of atrial flutter/fibrillation

Background: Remote rhythm monitoring with wearable devices is increasingly used especially for early detection of atrial fibrillation/flutter (AF/Afl), being the access to hospital discouraged, especially for frail elderly patients, due to the burden and risk of COVID-19 pandemic. Whereas devices using photo plethysmography (PPG) may misinterpret as AF pulse irregularities due to extrasystoles, patient-directed recording of a single (usually wrist-to-wrist) lead ECG (LEAD I) with hand-held devices or smartwatches have been developed to increase accuracy in AF detection. However, although recent studies validating such devices single-lead ECG recording have shown high sensitivity and specificity, false negative findings such as those reported here are still possible and must be prevented [1]. Purpose(s): Given previous experience of diagnostic uncertainty or failure of the smartwatch ECG (SW-ECG) LEAD I to detect AF/Afl, we have tested if false negative diagnosis could be avoided by recording in addition at least one right precordial (pseudo-V1) lead analyzed by a trained healthcare professional. Method(s): Over one calendar year observation, five patients with previous history of ablated supraventricular arrhythmias suffering sudden palpitations suspected of paroxysmal AF/Afl were instructed to record with their smartwatch at least one precordial lead in addition to LEAD I, to monitor ECG until the termination of symptoms. The SW-ECG strips were sent by telephone for professional interpretation. Diagnostic accuracy based on LEAD I and pseudo-V1 were independently validated by two cardiologists (diagnostic goldstandard - DGS). Result(s): 22 AF/Afl events occurred. Pharmacological cardioversion to sinus rhythm (SR) was obtained in 64%. 192 ECG strips were transmitted. 43,7% of the strips were automatically classified as not significant (or not valid ). Compared to DGS, out of 108 valid strips, correct automatic identification of AF/Afl was obtained in 36,4% with LEAD I, in 33,3% with pseudo V1 and in 54,5% with combined leads, respectively. Interestingly, the SW algorithm has wrongly diagnosed as SR, not only LEAD I, but also 39,4% of pseudo-V1 strips, despite clear-cut evidence of typical flutter waves (Figure 1), when RR intervals were regular due to high degree (e.g., 4:1) A-V block. Conclusion(s): With simple instructions, patients (or their relatives) can easily record an additional precordial (pseudo-V1) SW-ECG lead, that may enhance sensitivity and specificity for remote detection of AF/Afl. However, at present, visual interpretation of SW-ECG by a trained healthcare professional is still needed to guarantee 100% correct diagnosis of AF/Afl, crucial to reduce thromboembolic risk and timely initiate the appropriate treatments. The automatic interpretation of SW's ECG could be improved by appropriate training of a machine learning approach to detect and analyze the atrial waveform provided by an additional pseudo-V1 lead.

Medium term survival in patients over ninety years-old undergoing pacemaker implantation

Background: According to the Italian National Statistical Institute, the 12- month probability of survival in the general population between 90 and 94 years-old is 26%. Pacemaker (PM) implantation is often an urgent and necessary intervention, but in these patients the benefit in terms of quality and duration of life is unclear. Purpose(s): To analyze characteristics, outcome and factors associated with survival in patients who had turned 90 at the time of PM implant. Method(s): All the PM implants performed in patients >=90 from 1/1/2019 to 12/31/2020 were analyzed. Clinical parameters, device characteristics and follow-up data were extrapolated from the SuitEstensa Ebit reporting system;the exitus was verified by analyzing data from the Regional Health System. Result(s): During the study interval, among the 554 patients undergoing PM implantation in our Center, 69 (12%) were >=90 years-old (mean age 92+/-2 years, 46% male;complete/advanced AV block in 76%). Twenty-six (38%) patients had history of atrial fibrillation and 19 (28%) ischemic heart disease. A cardiological co-morbidity (excluding AF) was present in 23 patients (33%). Oncological, pneumological and neurological comorbidities were present in 12 (18%), 19 (28%) and 32 (46%) respectively. Renal impairment was present in 25 patients (36%). In 47 patients (68%) there were at least 2 co-morbidities. After implantation (single-chamber in 36, dualchamber in 25 and VDD single-lead dual-chamber in 8 patients) complications occurred in 3 patients (2 pneumothorax and 1 lead dislodgment). Remote monitoring was activated in 57 patients (83%). Within August 31st 2021 (mean follow-up 288+/-193 days) 24 patients died (35%, 219+/-241 days after implant). Five patients (19% of patients implanted in 2019) died within 12 months. No patients died for device malfunction. Three patients died because of COVID-19 pneumonia. Renal dysfunction (Hazard Ratio-HR 8.05, p=0.002) and the presence of 2 or more co-morbidities (HR 6.03;p=0.015) were associated with a higher risk of death at univariate analysis;other significant variables were diabetes (HR 2.34;p=0.038), left ventricular ejection fraction (LVEF) (HR 0.70 for 5% variation;p=0.005), walking impairment (HR 2.99, p=0.006), the presence of oncological (HR 2.21;p=0.003), pneumological (HR 2.55;p=0.024) and neurological (HR 1.90, p=0.007) comorbidities. At multivariable analysis the only significant parameter associated with survival was LVEF (0.76 for 5% difference;p=0.043) Conclusion(s): At our Center, patients >=90 years-old undergo PM implantation mainly for advanced AVB. The good survival in the medium term, even better than expected in the general population, does not justify a too conservative attitude especially, but exclusively, in patients with less comorbidities.

Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Protocol for Preparing for Competitions in Different Time Zones

The pandemic affected all branches of the country's economy, all categories of services, but also performance sports. With it, competitions appeared postponed without a precise date or even totally canceled. In performance sports, a major role was played by the uncertainty of the biggest competition in an athlete's life, the Tokyo competition. It was a great challenge for the coach to organize his training periods, so as to bring the athletes in the best shape, but also for the doctors and the medical staff to work on an adequate recovery, to support the physical effort through the most well-rated supplements, always adapting to changes and not least for athletes to resist physically and mentally and to find the motivation to continue the routine to achieve their goal, that of reaching Tokyo.Copyright © 2022 Andreea-Elena Siminiceanu, published by Sciendo.

Cardiac dysrhythmias among coronavirus-19 recovered symptomatic patients

Background: The coronavirus (COVID-19) pandemic, which affected millions of people worldwide, is associated with a chronic fatigue sequela, also known as long-COVID. While various adverse effects of COVID-19 on the cardiovascular system were reported, the prolonged sequela of COVID-19 on heart rhythm remains unknown. Aim(s): To describe the prevalence of cardiac dysrhythmias among patients who presented with Long Covid following recovery from COVID-19 infection. Method(s): We conducted a prospective study among 87 patients who suffered from Long Covid syndrome following recovery from COVID-19 and were treated in the COVID-19 recovery clinic between December 2020 and June 2021. All patients were referred for transthoracic echocardiography (TTE) and 24-hour Holter examination. Result(s): The mean age was 52+13 years, and 52 (59.8%) patients were females. Seventy-nine (90.8%) of the patients had normal sinus rhythm without evidence of any arrhythmias. Atrial premature beats were recorded in 70 (80.5%) patients with a median of 6/day (interquartile range 3-20/day;maximum: 5180/day). Ventricular premature beats were recorded in 50 (57.5%) patients with a median of 4/day (interquartile range 2-19/day;maximum: 6847/day). Overall, seven patients (8%) had sustained atrial dysrhythmias: One had atrial fibrillation, one had atrial flutter, and five had atrial tachycardia. Sixty-six (75.9%) patients underwent TTE, which was mainly unremarkable as 65 patients had a normal left ventricular function, and three (4.5%) patients had evidence of pulmonary hypertension. Discussion(s): Cardiac arrhythmias are not uncommon among symptomatic COVID-19 recovered patients. Atrial arrhythmias were most common, with an up to 8% incidence rate. These findings may suggest that atrial dysrhythmias may be associated with long-term symptomatic sequela of COVID-19 infection.