Context Bilateral adrenal hemorrhage is a rare condition with potentially life-threatening consequences as acute adrenal insufficiency. Early adrenal axis testing, as well as directed imaging, is crucial for immediate diagnosis and treatment. Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy and thromboembolic events. Case decription A 66-years-old woman presented with acute COVID-19 infection and primary adrenal insufficiency due to bilateral adrenal hemorrhage (BAH). She had also a renal vein thrombosis. Her past medical history revealed primary antiphospholipid syndrome (APLS). 4 weeks after discharge she had no signs of COVID-19 infection and her PCR test for COVID-19 was negative, but she still needed glucocorticoid and mineralocorticoid replacement therapy. The combination of APLS and COVID-19 was probably responsible of the adrenal event as a "two-hit" mechanism. Conclusions COVID-19 infection is associated with coagulopathy and thromboembolic events, including BAH. Adrenal insufficiency is life threatening, therefore we suggest to consider performing early adrenal axis testing for COVID-19 patients with clinical suspicion of adrenal insufficiency.

Objectives A significant proportion of COVID‐19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterisation and possible predictors were previously reported, there are conflicting data regarding the exact prevalence of arrhythmias. Clinically applicable algorithms to classify COVID patients' arrhythmic risk are still lacking, and are the aim of our study. Methods We describe a single‐centre cohort of hospitalised patients with a positive nasopharyngeal swab for COVID‐19 during the initial Israeli outbreak between 1/2/2020 and 30/5/2020. The study's outcome was any documented arrhythmia during hospitalisation, based on daily physical examination, routine ECG's, periodic 24‐hour Holter, and continuous monitoring. Multivariate analysis was used to find predictors for new arrhythmias and create classification trees for discriminating patients with high and low arrhythmic risk. Results Out of 390 COVID‐19 patients included, 28 (7.2%) had documented arrhythmias during hospitalisation, including 23 atrial tachyarrhythmias, combined atrial fibrillation (AF), and ventricular fibrillation, ventricular tachycardia storm, and 3 bradyarrhythmias. Only 7/28 patients had previous arrhythmias. Our study showed a significant correlation between disease severity and arrhythmia prevalence (P < .001) with a low arrhythmic prevalence amongst mild disease patients (2%). Multivariate analysis revealed background heart failure (CHF) and disease severity are independently associated with overall arrhythmia while age, CHF, disease severity, and arrhythmic symptoms are associated with tachyarrhythmias. A novel decision tree using age, disease severity, CHF, and troponin levels was created to stratify patients into high and low risk for developing arrhythmia. Conclusions Dominant arrhythmia amongst COVID‐19 patients is AF. Arrhythmia prevalence is associated with age, disease severity, CHF, and troponin levels. A novel simple Classification tree, based on these parameters, can discriminate between high and low arrhythmic risk patients.

Background. Opaganib is a selective sphingosine-kinase (SK)-2 inhibitor with anti-inflammatory and anti-viral properties. Methods. We provided opaganib on a compassionate-use basis to patients with severe COVID-19. Patients who required oxygen support via high-flow nasal cannula (HFNC) were offered the treatment. For comparison, we used a control group with same-sex, same-severity patients. Results. Seven patients received at least one dose of opaganib since April 2, 2020. One patient, who received both hydroxychloroquine and azithromycin, developed diarrhea and all his medications were stopped. This was the only adverse effect possibly related to opaganib. A second patient was weaned of oxygen and discharged after receiving two doses of opaganib. Therefore, five patients were included in this analysis. Baseline characteristics were not significantly different between cases and controls. Patients treated with opaganib had significantly faster increase in lymphocyte count. All other clinical outcomes had a non-statistically significant trend in favor of the treatment group: median time to weaning from HFNC was 10 and 15 days in cases vs. controls (HR= 0.3, 95% CI: 0.07-1.7, p=0.2) ,time to ambient air was 13 vs.14.5 days (HR=0.4, 95% CI: 0.15-1.5), none of the cases required mechanical ventilation compared with 33% of controls. Conclusion. In this small cohort of severe COVID-19 patients, opaganib was safe and well tolerated with improvement in both clinical and laboratory parameters in all treated patients. The efficacy of opaganib for COVID-19 infection should be further tested in randomized placebo-controlled trials.

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Introduction The acute disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS COV-2) is accompanied by a hypercoagulable state. Multiple publications have described the venous thromboembolic events associated with coronavirus disease 2019 (COVID-19) but arterial thromboembolic events have yet to be described. Cases description We describe five COVID-19 patients that developed severe morbidity as a result of occlusive arterial thromboembolic events occurring despite treatment with low molecular weight heparin. All cases presented with an acute confusional state and were accompanied by rapid elevations of lactate and D-dimers and leukocytes. The end organs involved were the kidneys, spleen, liver, lungs, central nervous system, intestines and limbs. Only one of the five patients survived. Conclusion COVID-19 is associated with not only venous but also arterial thromboembolic events. Further research is required to clarify the incidence, causes and possible modes of prevention of this potentially lethal disease complication.

Objectives: A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterization and possible predictors were previously reported, there are conflicting data regarding the exact prevalence of arrhythmias. Clinically applicable algorithms to classify COVID patients' arrhythmic risk are still lacking, and are the aim of our study. Methods: We describe a single center cohort of hospitalized patients with a positive nasopharyngeal swab for COVID-19 during the initial Israeli outbreak between 1/2/2020-30/5/2020. The study's outcome was any documented arrhythmia during hospitalization, based on daily physical examination, routine ECG's, periodic 24-hour Holter, and continuous monitoring. Multivariate analysis was used to find predictors for new arrhythmias and create classification trees for discriminating patients with high and low arrhythmic risk. Results: Out of 390 COVID-19 patients included, 28 (7.2%) had documented arrhythmias during hospitalization, including: 23 atrial tachyarrhythmias, combined atrial fibrillation (AF) and ventricular fibrillation, ventricular tachycardia storm, and 3 bradyarrhythmias. Only 7/28 patients had previous arrhythmias. Our study showed significant correlation between disease severity and arrhythmia prevalence (p<0.001) with a low arrhythmic prevalence among mild disease patients (2%). Multivariate analysis revealed background heart failure (CHF) and disease severity are independently associated with overall arrhythmia while age, CHF, disease severity, and arrhythmic symptoms are associated with tachyarrhythmias. A novel decision tree using age, disease severity, CHF, and troponin levels was created to stratify patients into high and low risk for developing arrhythmia. Conclusions: Dominant arrhythmia among COVID-19 patients is AF. Arrhythmia prevalence is dependent on age, disease severity, CHF, and troponin levels. A novel simple Classification tree, based on these parameters, can discriminate between high and low arrhythmic risk patients. WHAT'S KNOWN? • A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. • There is a correlation between disease severity in general and cardiac involvement specifically to occurrence of cardiac arrhythmias. • Arrhythmia characterization and possible predictors. WHAT'S NEW? • Using a 24-hour Holter monitoring among hospitalized COVID-19 patients, for better arrythmias detection. • Among of all hospitalized COVID-19 patients, 7.2% had new arrhythmias during hospitalization. • Classification tree which discriminate between high and low arrhythmic risk patients

Background The liberal administration of hydroxychloroquine‐sulphate (HCQ) to COVID‐19 patients has raised concern regarding the risk of QTc prolongation and cardiac arrhythmias, particularly when prescribed with azithromycin. We evaluated the incidence of QTc prolongation among moderately and severely ill COVID‐19 patients treated with HCQ and of the existence of concomitant alternative causes. Methods All COVID‐19 patients treated with HCQ (between Mar 1 and Apr 14, 2020) in a tertiary medical centre were included. Clinical characteristics and relevant risk factors were collected from the electronic medical records. Individual patient QTc intervals were determined before and after treatment with HCQ. The primary outcome measure sought was a composite end point comprised of either an increase ≥60 milliseconds (ms) in the QTc interval compared with pre‐treatment QTc, and/or a maximal QTc interval >500 ms Results Ninety patients were included. Median age was 65 years (IQR 55‐75) and 57 (63%) were male. Thirty‐nine patients (43%) were severely or critically ill. Hypertension and obesity were common (n = 23 each, 26%). QTc prolongation evolved in 14 patients (16%). Age >65 years, congestive heart failure, severity of disease, C‐reactive protein level, hypokalaemia and furosemide treatment, were all associated with QTc prolongation. Adjusted analysis showed that QTc prolongation was five times more likely with hypokalaemia [OR 5, (95% CI, 1.3‐20)], and three times more likely with furosemide treatment [OR 3 (95% CI, 1.01‐13.7)]. Conclusion In patients treated with HCQ, QTc prolongation was associated with the presence of traditional risk factors such as hypokalaemia and furosemide treatment.

Introduction Concomitant experimental/compassionate drug administration has been all-pervasive in the treatment of COVID-19 patients. The objective of this study was to study the relationship between patient severity, the number of experimental/compassionate medications received (main outcome measure), and patient outcomes [survival to hospital discharge and length of hospital stay (LOS)]. Methods Retrospective analysis of data collected in real time during the first pandemic wave in a tertiary care hospital. Data included patient demographics, comorbidities, admission vital signs, laboratory values, most extreme respiratory intervention during hospitalization, and data regarding treatment with compassionate/experimental drugs during their stay. Results Overall, 292 PCR-confirmed patients with symptoms of COVID-19 were studied (March/April, 2020). Increasing respiratory support correlated with both LOS and mortality. Patients were more likely to receive more than 1 experimental/compassionate drugs as respiratory support escalated, ranging from 3% ( n = 4/136) among patients on room air to 77.3% ( n = 17/22) of mechanically ventilated/ECMO patients ( P < 0.001, linear by linear association). The mean number of experimental/compassionate drugs received also increased with escalating respiratory support ( P < 0.001, one-way ANOVA). After adjustment for severity of patient condition, administration of more experimental/compassionate drugs was unrelated to survival ( P = 0.24), but was related to increased LOS ( P < 0.001). Conclusion Patients that were hospitalized in worse condition were more likely to receive more experimental/compassionate drugs. Treatment was unrelated to survival but may have been related to LOS. This finding raises questions regarding the results of studies on medication effects that adjusted for multiple drug administration. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01890-9.