Direct bilirubin and the neutrophil-to-monocyte ratio timely predict intensive care unit admission in patients with severe acute respiratory syndrome coronavirus-2 infection (COVID-19)

Objective: Intensive care units (ICUs) collapsed under the global wave of coronavirus disease 2019 (COVID-19). Thus, we designed a clinical decision-making model that can help predict at hospital admission what patients with COVID-19 are at higher risk of requiring critical care. Method(s): This was a cross-sectional study in 119 patients that met hospitalization criteria for COVID-19 including less than 30 breaths per minute, peripheral oxygen saturation < 93%, and/or >= 50% lung involvement on imaging. Depending on the need for critical care, patients were retrospectively assigned to ICU and non-ICU groups. Demographic, clinical, and laboratory parameters were collected at admission and analyzed by classification and regression tree (CRT). Result(s): Forty-five patients were admitted to ICU and 80% of them were men older than 57.13 +/- 12.80 years on average. The leading comorbidity in ICU patients was hypertension. The CRT revealed that direct bilirubin (DB) > 0.315 mg/dl together with the neutrophil-to-monocyte ratio (NMR) > 15.90 predicted up to correctly in 92% of the patients the requirement of intensive care management, with sensitivity of 93.2%. Preexisting comorbidities did not influence on the tree growing. Conclusion(s): At hospital admission, DB and NMR can help identify nine in 10 patients with COVID-19 at higher risk of ICU admission.Copyright © 2022 Sociedad Medica del Hospital General de Mexico.

Enoxaparin Sodium Biosimilar in the Prophylactic Treatment of Veinous Thromboembolism and Thromboembolic Disease: Prophyvar Study

Objectives: Varenox is the first locally manufactured and approved biosimilar in Algeria. It is an enoxaparin sodium (ES) with established good analytical characterization and manufacturing quality control. The aim of the PROPHYVAR study was to generate real-life data in routine practices and to assess the safety and tolerability in the prophylaxis of venous thromboembolism (VTE). Method(s): This is an observational, prospective, multicenter study, conducted between April 2021 and May 2022. The primary safety outcome was the incidence of Adverse Events (AEs) related to the study drug. A sample size of 500 patients was calculated to estimate the proportion of patients with AEs. Assuming that approximately 10% will be lost to follow-up or not evaluable, 550 patients were needed to describe the impact of Varenox use. Result(s): The study was conducted in 25 different sites in Algeria, in 4 therapeutic areas: ICU, orthopedic surgery, obstetrics and nephrology;550 patients were included and received at least one injection of Varenox. The mean age was 47 years, women in majority (62.5%). The patients were overweight or obese (53%), with a history of arterial hypertension (25%), diabetes (7.5%) and renal failure (6.4%). Reasons for hospitalization were mainly fracture (15.5%), pregnancy (8.3%), COVID-19 (7%) or cancer (7%). The majority of patients were treated at prophylactic dose of 0.4ml (80%) or 0.6ml (10%). The median duration of follow-up was 24 days. A total of 38 patients experienced at least one AE (6.9%, CI95=[4.9%;9.4%]). Related AEs were reported in 10 patients (1.8%), mainly in nephrology (N=7 arterio-venous fistula). VTE events were reported in 6 patients (1.1%, CI95=[0.2%;2%]). Conclusion(s): This study suggests that Varenox is safe in the prophylaxis of VTE. To our knowledge this is the first large study describing the use of ES in current medical practice in Algeria.Copyright © 2023

Effect of Anticoagulant Administration in patients Hospitalized with COVID-19 - A study from Lahore, Pakistan

Background: The recognition of the relationship between thromboembolism in COVID-19 and poor clinical outcomes led to the use of anticoagulants in patients diagnosed with COVID-19. Aim(s): To determine the effects of anticoagulants in COVID-19 patients and to compare the effect of oral, subcutaneous, and combined anticoagulants on patient outcomes. Study design: Retrospective cohort study Place and duration: A private tertiary care hospital, in Lahore, from 1st April 2020 to 30 Sep 2020 Methodology: Data were collected from electronic and paper records of admitted patients with a confirmed diagnosis of COVID-19 on PCR or with a radiological diagnosis of COVID-19. A total of 179 patients were included in the study, 172 were given anticoagulation, out of these, 74 were given oral anticoagulation, 73 were given subcutaneous and 24 were given combination of oral and subcutaneous anticoagulants. Result(s): Among 172 patients on anticoagulants, 41(23.8%) expired while 131(76.2%) recovered. Among 7(100%) patients on no anticoagulation, 1(14.3%) patient expired while 6(85.7%) recovered. 19(11%) patients on anticoagulation progressed towards the need for invasive ventilation while 152(89%) patients did not need invasive ventilation. Among patients on subcutaneous anticoagulants, 27(37%) expired while 46(63%) recovered. 8(33.3%) patients on combined anticoagulants expired while 16(66.7%) recovered. 6(8.1%) patients on oral anticoagulants expired while 68(91.9%) recovered. Conclusion(s): Anticoagulation improves the outcome of COVID-19 patients and oral anticoagulation is better than subcutaneous and combined anticoagulation.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Drug utilization study in patients affected with COVID-19 in a dedicated COVID hospital

Background: There exists a treatment dilemma regarding the optimal and effective use of therapeutic drugs (hydroxychloroquine/chloroquine/azithromycin) for COVID-19. Furthermore, with changing guidelines, the data on drug utilization patterns across India are limited. Hence, this study was conducted to assess the prescription pattern and drug utilization trends in COVID-19 patients with the aim to study the drug utilization pattern in patients affected with COVID-19 in a dedicated COVID-19 hospital. Aims and Objectives: The objectives of the study are as follows: (1) To study drug utilization patterns according to the severity of the disease. (2) To study the prevalence of adverse drug reactions (ADRs). Materials and Methods: Data were collected retrospectively from 100 medical records of patients 18 years irrespective of sex admitted in the COVID ward and ICU of a dedicated COVID hospital from May to August 2020. Pregnant and lactating women were excluded from the study. ADRs reported were also analyzed. Results: About 71% were mild in this study, 18% were moderate, and 11% were severe COVID-19 patients. Overall, the most common drugs prescribed were multivitamins, followed by pantoprazole, paracetamol, and azithromycin. Hydroxychloroquine was prescribed in 22%, favipiravir in 7%, and remdesivir in 3% of cases. The majority of moderate COVID patients received injectables piperacillin-tazobactam, methylprednisolone, and enoxaparin. The mean number of medications, duration of admission, and number of days on oxygen were higher and significant in moderate compared to mild and severe COVID patients. Overall, ADRs were encountered in 9% of cases. Conclusion: The prescribed pattern of drugs was by the national standard guidelines. Multivitamins, followed by pantoprazole, paracetamol, and azithromycin dominated the prescription pattern. Polypharmacy was encountered, which needs to be addressed for the rational use of drugs.

Complications Of A Severe Case Of Multisystem Inflammatory Syndrome In Children

Case Presentation: A 10 year old male with prior COVID-19 exposure presented with 7 days of fever, rash, cough, vomiting, and hypotension. Laboratory evaluation was notable for SARS-CoV2 antibodies, elevated cardiac enzymes, BNP, and inflammatory markers. Initial echocardiogram showed normal cardiac function and a small LAD coronary aneurysm. He was diagnosed with Multisystemic Inflammatory Syndrome in Children (MIS-C) and given methylprednisolone and IVIG. Within 24 hours, he developed severe LV dysfunction and progressive cardiorespiratory failure requiring VA-ECMO cannulation and anticoagulation with bivalirudin. Cardiac biopsy demonstrated lymphocytic infiltration consistent with myocarditis. On VA-ECMO, he had transient periods of complete AV block. With immunomodulator treatment (anakinra, infliximab) and 5 days of plasmapheresis, inflammatory symptoms and cardiac function improved. He weaned off ECMO, and anticoagulation was transitioned to enoxaparin. He had left sided weakness 5 days later, and brain MRI revealed an MCA infarct. Ten days later, he had focal right sided weakness and repeat MRI showed multiple hemorrhagic cortical lesions, thought to be thromboembolic with hemorrhagic conversion secondary to an exaggerated inflammatory response to an MSSA bacteremia in the setting of MIS-C. Enoxaparin was discontinued. After continued recovery and a slow anakinra and steroid wean, he has normal coronary arteries, cardiac function, and baseline ECG but requires ongoing neurorehabilitation. Discussion(s): COVID-19 infection in children is often mild, but MIS-C is an evolving entity that can present with a wide range of features and severity. This case highlights two concepts. While first degree AV block is often reported in MIS-C, there is potential for progression to advanced AV block. Close telemetry monitoring is critical, especially if there is evidence of myocarditis. MIS-C shares features with Kawasaki disease, with a notable difference being a higher likelihood of shock and cardiac dysfunction in MIS-C. In MIS-C patients with cardiovascular collapse requiring ECMO, there is a risk for stroke. There should be a low threshold for neuroimaging and multidisciplinary effort to guide anticoagulation in these complex cases.

Anti-Xa guided twice daily enhanced anticoagulation for severe COVID-19 patients in intensive care unit setting: outcomes, incidence of pulmonary embolism and complications

Introduction: Pulmonary embolism (PE) is a major cause of intensive care unit (ICU) mortality and morbidity [1]. Optimal venous thromboembolism preventive strategy in COVID-19 patients remains a controversial issue. Therapeutic anticoagulation in the context of severe COVID-19 without a formal indication does not appear to offer a survival advantage and was associated with increased risk of major bleeding episodes. Locally, we adopted an enhanced anticoagulation (enoxaparin twice a day) pathway guided by anti-Xa levels. Method(s): This is a retrospective cross-sectional single-center study between March 2020 and March 2021. All patients admitted to the intensive care unit at University Hospital Southampton with diagnosis of COVID-19 confirmed via a reverse-transcriptase-polymerase-chain reaction (RT-PCR) test were included in this study. Result(s): There were 292 admissions included in the study with a mean age of 60 (+/- 15). 67.1% received enhanced anticoagulation titrated according to anti-Xa levels. The median day 7 trough and peak anti-Xa levels were 0.33 (IQR 0.18-0.41) and 0.54 (IQR 0.33-0.68) respectively. 62 patients had CTPA for clinical suspicion of pulmonary embolism and 11 were positive. The overall incidence of PE was 3.8%. The distribution of PE was mostly bilateral segmental or unilateral segmental. There were no lobar or main pulmonary artery pulmonary embolism. There were 9 major bleeding episodes in those received enhanced anticoagulation. Conclusion(s): For critically ill COVID-19 patients, anti-Xa guided enhanced anticoagulation protocol proved to be associated with lower than anticipated incidence of PE with minimal clot burden. Randomised controlled trials are required to explore this concept further.

A Joint Analysis of Two Randomized Controlled Trials on Enoxaparin for Covid-19

Background: COVID-19 carries a high risk of vascular thrombosis. This joint analysis of two randomized-controlled trials (RCTs) aims to assess the safety and efficacy of enoxaparin at therapeutic dose compared to prophylactic dose in people hospitalized with COVID-19. Method(s): A joint analysis of two RCTs, COVID-19 HD (NCT044082359) and EMOS-COVID (NCT04646655), was performed. Both studies enrolled inpatients with COVID-19- associated respiratory compromise (as identified by respiratory rate >=25 breaths/min or arterial oxygen saturation <=93% at rest or PaO2/FiO2 <=300 mmHg for COVID-19 HD and by PaO2/FiO2 <=250 mmHg for EMOS-COVID) and/or coagulopathy (D-dimer > 2000 ng/ml for both RCTs or sepsis-Induced coagulopathy score >4 for COVIDHD). In both RCTs patients were randomly assigned to two arms: enoxaparin at prophylactic dose (standard 4.000 IU;in the EMOS-COVID 6000 IU if body weight >100 kg) and at therapeutic dose (70 U/Kg every 12 h). The primary efficacy endpoint of the joint analysis was clinical worsening, defined as the occurrence of at least one among: in-hospital death;acute myocardial infarction;symptomatic arterial or venous thromboembolism;need of either Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) in patients who were in standard oxygen therapy at randomization;need for IMV in any patient. The primary outcome was assessed as time-to-event, described with hazard ratio (HR) and with Kaplan-Meier survival estimate. The primary safety endpoint was major bleeding for both trials and for the joint analysis. Result(s): COVID-19 HD enrolled 142 people between July 2, 2020 and February 15, 2022, while EMOS-COVID enrolled 141 people from July 27, 2020 to June 5, 2021, resulting in 283 patients included in this joint analysis. Two-hundredseven (73.1%) were males, with a mean age of 61.1 years (SD +/-10.7), a mean BMI of 29.7 kg/m2 (SD +/-5.0), and 115 (40.6%) were on NIV or Cpap at randomization, with no significant difference between the study groups. 21/139 people in the high dose group reached the primary endpoint compared to 32/144 in the prophylactic group (HR 0.63, 95%CI 0.36 to 1.10). Figure 1 shows the Kaplan- Meier survival estimates of clinical worsening. No major bleeding was observed during the study time. Conclusion(s): The results of this joint analysis did not highlight significant differences in clinical worsening between COVID-19 patients that received enoxaparin at therapeutic compared to prophylactic dose. (Figure Presented).

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).

Effects of some biological factors on Coronavirus

This research was been adopted to study the relationship between Covid and some necessary biological factors in human body and how these factors affected, This studying included three stages (Sever - Moderate - Mild) it was studied 20 patient for every stage and monitor the biological factors during infection and after infection.Copyright © 2023, Codon Publications. All rights reserved.

Enoxaparin Use in Hospitalized SARS-CoV-2-Positive Patients with Elevated D-Dimer: A Pilot Study.

INTRODUCTION: The SARS-CoV-2 is a human pathogenic coronavirus that causes a respiratory tract infection, which may lead to systemic hyper-inflammation that is associated with a hypercoagulable state. Anticoagulation as an adjunct may decrease thrombi formation. OBJECTIVES: This study aims to evaluate the efficacy and safety of enoxaparin for the prevention of thrombotic events in hospitalized SARS-CoV-2 patients with elevated D-dimer. METHODS: A single-center retrospective cohort study was conducted to evaluate three enoxaparin dosing regimens: full treatment (1 mg/kg SC Q12H or 1.5 mg/kg SC Q24H), intermediate (.5 mg/kg SC Q12H or 1 mg/kg SC Q24H), and prophylaxis (40 mg SC Q24H). The primary endpoint evaluated the percentage of patients who developed a venous thromboembolism (VTE). The secondary endpoints evaluated the development of a major bleed, mechanical ventilation need, and death. RESULTS: Forty-five patients were included with 27, 8, and 10 participants in the full treatment, intermediate, and prophylaxis arms, respectively. Six patients developed a VTE: 3, 1, and 2 in the listed above groups, respectively (P = .83). Twenty patients died: 11, 3, and 6, respectively (P = .64). Four patients developed a major bleed: 1, 1, and 2, respectively (P = .17). Six patients required intubation: 1, 2, and 3 in the arms, respectively (P = .043). CONCLUSION: The study did not find a difference in respect to the development of a VTE between the three investigated doses of anticoagulation. However, our findings suggest that treatment dose of enoxaparin might be associated with lower risk for mechanical ventilation in hospitalized COVID-19-positive patients with elevated D-dimer.

Low molecular weight heparin in COVID-19: benefits and concerns.

Since its emergence, the COVID-19 pandemic had a dramatic impact on the public health worldwide and it scarred the medical, economical, and social determinants of health. Even after the significant vaccination advances, the disease of SARS-CoV-2 can manifest in severe presentations with life-threatening thromboembolic and multi-organ complications leading to notable morbidity and mortality. Clinicians and researchers are on continuous pursuit of investigating different approaches in the attempt to prevent the infection and minimize its severity. Although the COVID-19's pathophysiology remains relatively unclear, it is well established now that coagulopathy, systemic thrombotic propensity, and a robust immunoinflammatory response are some of the most important determinants of its morbidity and mortality. Accordingly, research efforts have focused on addressing the inflammatory and hematological cascades using available agents to avoid thromboembolic events. Several studies and investigators have emphasized the importance of Low molecular weight heparin (LMWH), namely, Lovenox, in addressing these sequelae of the COVID-19 disease, either prophylactically or therapeutically. This review explores the benefits and concerns of employing LMWH, a widely used anticoagulant, in COVID-19 disease. It delves into Enoxaparin as a molecule, along with its pharmacology, mechanism of action, and clinical uses. It also reviews the current high-quality clinical evidence that highlight the role of enoxaparin in SARS-CoV-2 infection.

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

Repeated COVID-19 infection in recipients of post-living donor liver transplantation: Two real-life cases

COVID-19 is an emerging pandemic. The course and management of the disease in the liver transplant setting may be difficult due to a long-standing immunosuppressive state. In Egypt, the only available option is living donor liver transplantation (LDLT). In our centre, we have transplanted 440 livers since 2008. In this study, we report a single-centre experience with COVID-19 infection in long-term liver transplant recipients. A total of 25 recipients (5.7 %) had COVID-19 infections since March 2020. Among these recipients, two developed COVID-19 infections twice, approximately three and two months apart, respectively.Copyright © 2021 The Author(s)

Acute exantematic pustulosis generalized by meropenem, differential diagnosis with COVID

Case report We present the case of a 63-year- old man with two consecutive admissions, due to COVID19 infection and subsequent bacterial superinfection. Three days after the second admission (04/28), and 43 days from the beginning of the infection an assessment by dermatology and allergology is then requested. The patient had generalized erythematous maculopapular rash in the trunk, back, groin and limbs. On the left side and back, pustular lesions not focused on follicles were also added, with a fever of 37.7degreeC. There were no oral and genital lesions. No psoriasis. The drugs used during the present and previous admissions were reviewed. Previous admission (04/04-22/ 20): Linezolid, ciprofloxacin, meropenem 04/13-22, piperacillin/tazobactam, hydroxychloroquine, azithromycin, ceftriaxone. Upon discharge amoxicillin/acid clavulanic. Present admission (04/25) Cutaneous reaction 04/28. 04/25: meropenem, paracetamol, enoxaparin, insulin, omeprazole, venlafaxine. 04/26: Darbepoetin, furosemide, mycophenolate in single dose. 04/27: Linezolid, macrogol, Clopidogrel, Magnesium, Calcitriol. Medical records: DM type 2, liver transplantation due to HCV cirrhosis, HCV recurrence, uninodular hepatocarcinoma, advanced CKD, secondary hyperparathyroidism, multiple neurological antecedents. We performed a detailed study. We hypothesized with a pharmagological/ drug reaction with several drugs possibly involved and our main suspicion was an allergic reaction to beta-lactams. Biopsy: Subcorneal pustules, basal spongiosis and presence in the superficial dermis of edema and an inflammatory infiltrate with abundant neutrophils. No fungi. Findings compatible with clinical diagnosis of generalized acute exanthematic pustulosis (PEGA). Immunohistochemical study Covid19. (Jimenez Diaz Foundation) Finely granular positivity in endothelium and more coarse in sweaty epithelium. Neutrophilic superficial inflammatory component with presumably spure staining. ACe-2 (positive external control) is not detected. The patient presents a EuroSCAR score of 9, sum of the clinic and the pathological anatomy, and therefore defined diagnosis. Clinical diagnosis: PEGA secondary to meropenem. Conclusion(s): We present the case of a PEGA by meropenem, not very often described in the literature. We highlight the importance of differential diagnosis with viral infections. Skin tests, especially epicutaneous tests, are key to the diagnosis. (Figure Presented).

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).

Monotherapy versus polytherapy of enoxaparin and hydroxychloroquine for the treatment of COVID-19: A randomized controlled clinical trial.

Objectives: The current study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine (HCQ) used as monothrapy or polytherapy versus standard care alone in Coronavirus 2019 (COVID-19) infected patients. Methods: The current study included two hundred patients with laboratory confirmed COVID-19 infection. Patients admitted to hospital were randomly allocated into four groups: group I: received standard COVID-19 therapy, group II: received Enoxaparin 40mg/day subcutaneously (SC) plus standard therapy, group III: received 400 mg/day HCQ plus standard therapy & group IV: received a combination of 400 mg/day HCQ and Enoxaparin plus standard COVID-19 therapy. The disease progression was evaluated by duration to a negative polymerase chain reaction (PCR), length of hospital or Intensive Care Unit (ICU) stay, and mortality rate. The safety of treatments was evaluated by measuring adverse effects. Results: The length of hospital stay, ICU admission and mortality were significantly decreased in Enoxaparin plus standard COVID-19 therapy group versus other groups. Conclusion: These findings suggest that Enoxaparin was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits.

Maternal and Fetal Effects of COVID-19 Virus on a Complicated Triplet Pregnancy: a Case Report

Background: Coronavirus disease 2019 (COVLD-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case. Case presentation: The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition. Conclusion(s): This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.Copyright © 2022 Goldstein and Associates. All rights reserved.

Development and Validation of Analytical HPLC Method for Identification and Assay of Enoxaparin Sodium in Injectable Preparations

Introduction. Enoxaparin sodium-containing drugs are included in relevant protocols for COVID-19 therapy. An increase in the production volume of such drugs leads to a demand for available and precise methods of identification and quantitative measurement of the active ingredient in the preparations. Considering the fact that pharmacopoeial methods require significant amount of expensive standards and reagents that are unavailable for numerous laboratories, it is relevant to develop a more available method that will accelerate and make cheaper the process of quality control for enoxaparin sodium-containing preparations. Aim. To develop and validate a simple, economic, and precise method of gel-permeation HPLC with the application of a refractive index detector for the evaluation of enoxaparin sodium in preparations for injection. Materials and methods. Samples of enoxaparin sodium-containing substances and commercial preparations were studied. The identification and quantitative content of the active ingredient were performed by the method of gel-permeation HPLC using a 1260 Infinity (Agilent Technologies, USA) chromatograph equipped with a refractive index detector. Results and discussion. The authors analyzed standard validation characteristics: specificity, linearity, precision, and accuracy of the method. The analysis revealed high specificity and suitability of the proposed method to chromatographic symmetrical multiprocessing systems. The method is recommended for routine control of finished and semi-finished pharmaceutical preparations containing from 25 to 200 mg/ml of enoxaparin sodium-containing. Conclusion. The proposed method can be used for routine quality control of enoxaparin sodium-containing preparations for injection. © Pshenichnov E. A., Kondrasheva K. V., 2023.

Thrombotic Presentation of MIS-C After COVID-19 Infection in a Nine-Year-Old Boy

Introduction: SARS-CoV-2 is the cause of the recent pandemic. Although children are less affected by the virus, they can present with various presentations ranging from asymptomatic or fatigue and fever to multisystem inflammatory syndrome in children (MIS-C). Case Presentation: In this case report, we presented a case of a 9-year-old boy who presented with bilateral deep vein thromboses (DVTs) of the femoral and iliac veins as his main presentation of MIS-C, which occurred following a COVID-19 infection. A complete history was taken from the patient, and then a series of tests, including complete blood counts (CBCs), liver function tests (LFTs), and D-dimer, were performed. Bilateral doppler sonography to confirm the event and its location, as well as a decent follow-up method, were performed. Levels of anti-Xa assays followed the toxic levels of enoxaparin. The child was treated with a regimen of enoxaparin and corticosteroids, with a dosage of 1 mg/kg/12 h for both. The child was in the hospital for two weeks, after which he got better and was managed as an out-patient with a regularly scheduled appointment. Finally, once the radiologic evidence of DVTs was cleared, the patient tapered off his enoxaparin over the course of three weeks. Conclusion(s): Thrombotic events following COVID-19-associated MIS-C are an unlikely yet deadly event, especially in children. Prompt treatment with anticoagulants and corticosteroids alongside monitoring the patients are strongly advised.Copyright © 2022, Author(s).