The use and safety risk of repurposed drugs for COVID-19 patients: lessons learned utilizing the Food and Drug Administration's Adverse Event Reporting System.

Objectives: This study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic. Methods: A retrospective observational study was conducted utilizing the Food and Drug Administration's Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio. Results: A total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95-62.18]; PRR 42.41 [95% CI 32.25-55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46-5.19] and 2.96 [95% CI 2.66-3.29], respectively. Conclusion: Our study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.

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).

Using Objective Electrocardiographic Data To Better Predict Mortality In Patients Hospitalized With COVID-19

Background: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. Method(s): Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. no mortality (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. A subgroup analysis of 651 patients who underwent at least 1 ECG in the 12 months prior to their COVID hospitalization were analyzed to detect statistically significant differences in conduction intervals pre and post SARS-CoV-2 infection. Result(s): According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. Our subgroup analysis of the 651 patients mentioned above yielded no statistically significant differences in conduction intervals pre & post SARS-CoV-2 infection. Conclusion(s): : Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. Subgroup analysis of 651 patients showed no statistically significant differences in conduction intervals pre and post SARS-CoV-2 infection. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.Copyright © 2022

Major Drugs Used in COVID-19 Treatment: Molecular Mechanisms, Vali-dation and Current Progress in Trials

Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.

Alternative Management of Cushing's Syndrome During Covid-19 Pandemic

Cushing's syndrome results from prolonged exposure to glucocorticoids. Surgery is often the first-line treatment for this condition, regardless of etiology. However, the COVID-19 pandemic caused a decrease in surgical procedures due to the risk of infection transmission. There are still emergency cases of Cushing's syndrome that are admitted to the hospital and require urgent management. The current treatment should be focused on medical management and endovascular embolization in selective cases. Embolization can be performed in facilities where there aretrained personnel with experience in adrenal embolization. Surgery, which traditionally is a first-line therapy, can increase the risk of infection, therefore, it should be avoided. The current review provides a brief description of the possible options for the management of adrenal Cushing's syndrome during the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Tocilizumab- a Treatment Option for Torsades De Pointes in Covid-19 Patients

Background The incidence of ventricular arrhythmias (VA) in Coronavirus disease 2019 (COVID-19) patients ranges from 1.6 to 5.9%. COVID-19 can trigger a systemic inflammatory response, which may unmask arrhythmias. Here we discuss a challenging case of COVID-19 that manifested as recurrent Torsades de Pointes (TdP). Case A 39-year-old female with no known past medical history presented with a complaint of multiple syncopal episodes in the last two days. Initial electrocardiograms (EKG) showed a heart rate of 62 with frequent premature ventricular contractions (PVCs) and a prolonged corrected QT(QTc) interval of 520ms. Frequent PVCs soon converted to TdP with loss of consciousness which was managed with successful direct current cardioversion (DCCV). However, the patient relapsed into TdP, warranting another successful DCCV. COVID-19 workup came back positive. Electrolytes were within normal limits;however, C-reactive protein (CRP) and troponin T levels were elevated. Decision-making The patient was started on intravenous (IV) magnesium for 24 hours. Following another episode of self-limiting TdP, IV isoproterenol was started, and tocilizumab was given. An echocardiogram showed no evidence of structural heart disease. During the hospital course, telemetry showed PVCs that decreased in frequency paralleled with a decrease in CRP and troponins. Repeat EKGs showed normalization of QTc interval. The patient declined implantable device placement or procedures and was eventually discharged with a heart monitor and a beta blocker. On follow-up, the patient denied any symptoms since the discharge, QTc remained normal, and the heart monitor did not show any VA. Conclusion Management of TdP generally involves magnesium, IV isoproterenol, and transvenous pacing. However, as described in this case, tocilizumab can cause QT interval shortening and a reduction in CRP and cytokine levels and may be beneficial for use in COVID-19 patients with QT prolongation and VA, including TdP. There are no strict guidelines for arrhythmias in COVID-19 patients. Accordingly, more studies need to be done to follow this patient population managed with tocilizumab for their eventual outcomes.Copyright © 2023 American College of Cardiology Foundation

Assessment and management of the SARS-CoV-2 infection: A secondary center experience: Approach to COVID-19 infection

Aim: The aim of the study was to evaluate the management and outcomes of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a secondary hospital. Material(s) and Method(s): This study included 699 hospitalized patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 on chest computed tomography (CT). Demographics, comorbidities, initial laboratory tests on admission, treatment modalities, complications and outcomes were evaluated retrospectively. Result(s): The mean age was 57.0+/-15.6 (range:16-94 years), and male to female ratio was 1.24;58.7% of the patients had at least one underlying comorbidity, the most common was hypertension;18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3% had increased lactate dehydrogenase, and 58.5% had increased D-dimer. Chest CT revealed moderate and severe stages in 57.9% of the patients. Hydroxychloroquine was given to 37.2% and favipiravir to 67.1% of the patients. No significant difference was observed between treatment groups in terms of mortality (P=0.487);5.8% of the patients were transferred to the ICU, 75.6% of whom needed non-invasive and 36.5% invasive mechanical ventilation. The overall case-fatality rate was 0.9. Discussion(s): Older age, male gender, low lymphocyte count, CT findings, including bilateral involvement and severe stage were significantly associated with poor prognosis and mortality.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Antibiotic Use in Acute Upper Respiratory Tract Infections

Upper respiratory tract infections are responsible for millions of physician visits in the United States annually. Although viruses cause most acute upper respiratory tract infections, studies show that many infections are unnecessarily treated with antibiotics. Because inappropriate antibiotic use results in adverse events, contributes to antibiotic resistance, and adds unnecessary costs, family physicians must take an evidence-based, judicious approach to the use of antibiotics in patients with upper respiratory tract infections. Antibiotics should not be used for the common cold, influenza, COVID-19, or laryngitis. Evidence supports antibiotic use in most cases of acute otitis media, group A beta-hemolytic streptococcal pharyngitis, and epiglottitis and in a limited percentage of acute rhinosinusitis cases. Several evidence-based strategies have been identified to improve the appropriateness of antibiotic prescribing for acute upper respiratory tract infections.Copyright © 2022 American Academy of Family Physicians.

A case of de novo seronegative inflammatory oligoarthritis associated with COVID-19 infection

Infection with SARS-CoV-2 (COVID-19) virus is characterized by an acute respiratory viral illness, often accompanied by extrapulmonary manifestations. Musculoskeletal symptoms such as myalgias and arthralgias are observed in 60 - 70% of cases. Inflammatory arthritis associated with SARS-CoV-2 infection has been reported in the literature, however, nearly all such cases describe a post-viral or reactive phenomenon occurring a few weeks following the infection. We report a unique case of de novo arthritis at the onset of a confirmed COVID-19 infection in a 55-year-old woman. Magnetic resonance imaging demonstrated synovial enhancement consistent with synovitis. Her disease was deemed refractory after failing several immunosuppressive agents. Lastly, we compare our patient's clinical presentation with two other similar cases to understand the natural history of this emerging syndrome.Copyright © 2022

Hydroxychloroquine and COVID-19 - A narrative review.

COVID 19 infection is unarguably the worst pandemic of this century. Till date there is no promising drug and vaccine available to treat this deadly viral infection. In the early phase chloroquine phosphate and hydroxychloroquine sulphate have been used to fight this illness on the basis of handful observational and small randomized and small-randomized studies. The paucity of clinical evidences of an unequivocal beneficial effect of chloroquine and hydroxychloroquine on COVID-19 has resulted in the passionate use of the drug for moderate to severe cases only and stimulated the need for large clinical trials for this and other molecules. In this review, we describe in brief the mechanism of action, the clinical studies, factors for cardiac toxicity, guidelines and future directions for hydroxychloroquine use in management of COVID-19 infection.

Takotsubo cardiomyopathy presenting with QT prolongation and Torsade de pointes in the setting of coronavirus disease 2019.

Cardiovascular complications resulting from coronavirus disease 2019 (COVID-19) are occasionally observed; however, takotsubo cardiomyopathy (TCM) with QT prolongation and Torsade de pointes have rarely been reported. We herein present a case of TCM that occurred after QT prolongation and Torsade de pointes. A 58-year-old woman was admitted because of COVID-19 pneumonia. Seven days after admission, she had a sudden loss of consciousness without any precursor of cardiovascular disease. Monitoring electrocardiogram indicated Torsade de pointes and a prolonged QT interval. Emergency cardiac catheterization revealed the presence of TCM. She received favipiravir and steroids, followed by rehabilitation, which improved her condition. Routine electrocardiography screening is considered for patients with COVID-19 because asymptomatic TCM could be detected.

Hydroxychloroquine induced QT prolongation in a schizoaffective patient being treated for a COVID-19 infection: A Case Report

Introduction: Hydroxychloroquine an antimalarial medication has been approved in March 2020 by FDA for treatment of hospitalized patient with COVID-19 infection. Even thus, its efficacy has been controversial, it still being used worldwide. This medication also causes some serious side effects. Here we present a case of a woman with a very long history of treatment resistant schizoaffective disorder, on clozapine, who develops QT prolongation after receiving hydroxychloroquine for the treatment of COVID-19 infection. Objective(s): Despite the controversy, this case aims to shed light on the importance of monitoring QTc via EKG in patient receiving hydroxychloroquine7 . More importantly to avoid antipsychotic while patient is receiving this medication since both hydroxychloroquine and most antipsychotic can increase QTc. Method(s): This case report was written by reviewing chart of the patient and also via direct interaction and interviews with the patient. Result(s): This case report showed and increased in QTc interval after receiving hydroxychloroquine, which is also reported by others including Moussa Sleh et al in their article on Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection4 . The increase in Qtc could have been worse if Clozapine was not stopped during this time. Conclusion(s): COVID-19 pandemic has caused more than 700000 deaths around the globe and more than 150000 deaths in the United States of America. Psychiatric patients are also getting hospitalized and receiving treatment with hydroxychloroquine. Holding antipsychotics and monitoring of QTc via EKG resulted crucial in limiting the adverse effect of QT prolongation of both medications.

A Study to Compare the Prolongation of the Corrected QT Interval of Rheumatoid Arthritis Patients on Hydroxychloroquine

Background: For rheumatoid arthritis (RA) patients, hydroxychloroquine (HCQ) is a staple treatment. Concerns about its cardiovascular safety have been raised after reports of its use and fatal arrhythmias in individuals with coronavirus illness 19. Aims and objectives: To examine the relationship between HCQ use and corrected QT (QTc) length in RA patients. Material(s) and Method(s): Hundred subjects (age >= 18 years) were studied after dividing them in to Cases (n=50;patients with RA taking HCQ) and Control (n=50;patients without RA not taking HCQ) at the Department of General Medicine of a tertiary care center in Madhya Pradesh. Patient characteristics and laboratory measures, including rheumatoid factor hemoglobin, white blood cells count, platelets, erythrocyte sedimentation rate (ESR), random blood sugar, urea, Creatinine, SGOT, SGPT, serum electrolytes, calcium, and magnesium level, were assessed. QTc length was obtained with the help of 12-lead ECG. Result(s): Incidence of QTc prolongation in patients with RA was 11%. Odds for prolonged QTc interval for patients with age >50 years was 3.500 (95% CI = 0.865-14.155), serum calcium <8 was 2.400 (95% CI = 0.540-10.666), and ESR >20 was 0.756 (95% CI = 0.640-0.892). A significant positive correlation was obtained between prolonged QTc with age (r=0.283;p=0.046). Conclusion(s): There is a significant increase in risk of QTc prolongation with the use of HCQ in patients with RA. Copyright © 2022, Dr Yashwant Research Labs Pvt Ltd. All rights reserved.

Effect Of Covid-19 Infection On Qtc Prolongation

Background Objective: What is the association between COVID-19 infection and QTc changes? Coronavirus SARS-COV2 uses angiotensin-converting enzyme receptors 2 (ACE2) on host cells to enter into human cells. These receptors are expressed on the heart cells among other major cells. This is one of the most accepted theories for direct cardiac cell injury of COVID-19disease and associated cardiorespiratory manifestations. COVID-19 infection leads to unstable myocardial cell membranes, by causing hypoxia, myocarditis, myocardial ischemia, and abnormal host immune response. This is the main reason behind Arrhythmia and EKG changes during COVID19 infection. But the specific effect on QTc has not been studied well so far, so our research try to study this connection. Method(s): This is an observational retrospective hospital chart review involving 320 adult participants diagnosed with COVID-19 infection at our facility. After applying the exclusion criteria, 130 participants remained, who were distributed into two groups. One group with long QTc and one group with normal QTc. Data was collected and demographics were recorded using Excel and SPSS, then compared using a student's t-test for independent groups. The quantitative data are summarized by the mean and standard deviation (SD). Statistical significance was taken as P <0.05. Result(s): A total of 63 participants (48.4% of total 130 participants) met the criteria for long QTc, and a total of 67 participants(51.5%) had normal QTc (P < 0.001). There was no statistically significant mortality outcome (0.8% vs. 3.8%, P = 0.21). Conclusion(s): Our study showed 48.4% participants having an increase in QTc during COVID-19 infection, (20% of 320 total admissions). This observation is very important to help healthcare providers to gaina better understanding of this disease.

Cardiovascular manifestation in multisystem inflammatory syndrome in children temporally associated with COVID-19-single center experience

Background and Aim: Cardiovascular manifestations are common (35-100%) in multisystem inflammatory syndrome in children (MIS-C), including ventricular dysfunction, shock, coronary artery dilation, pericardial effusion and conduction abnormalities. Our study aimed to analyse cardiovascular involvement in our patients with MIS-C treated in our hospital. Method(s): The retrospective cohort study included all patients with MIS-C treated from April 2020 to December 2021 in the Mother and Child Health Institute of Serbia. In every case, cardiovascular manifestations were analysed: ventricular dysfunction, coronary artery dilatation, pericardial effusion, shock and ECG changes. Result(s): The study included 77 patients, 45 boys and 32 girls, aver-age years of age 9.3 +/- 4.8. Elevated cardiac troponin I and pro-BNP were observed in 35.9% and 87.8% of patients, respectively. Myocardial dysfunction was observed in half of our patients (50.6%), with an average ejection fraction of 50.5 +/- 8.9%. Children older than 10 years had 4 times higher chances for myo-cardial dysfunction (OR 4.3, 95%CI 1.6-10.8;p = 0.003). Shock syndrome had 21.1% of children on admission, while 5.3% devel-oped shock during the in-hospital stay. Transient coronary artery (CA) dilatation was observed in 6.5% of patients;left CA in 3 pts (Z score +2,95 +/- 0.3), right CA in one patient (Z score +2), and in one LCA and RCA (RCA Z score 2.6). Transient CA dilatations were observed only in patients with KD-like clinical presentation (5/54 pts). Mild pericardial effusion with spontaneous resolution was detected in 28.6% of children, while one female adolescent had severe pericardial effusion with threatening cardiac tamponade. On the standard ECG, 53% of children had negative T wave in inferior or/and precordial leads averagely on day 2 (IQR 1-3 day);transient QTc prolongation was registered in 46% of patients, averagely on day 7 (IQR 5-9). Sinus bradycardia and coronary rhythm were registered in 42.1% of patients, while premature ven-tricular beats were observed in 2.7% of pts. left ventricle thrombus was detected in one patient with normal echocardiography find-ing. In this patient, increased activity of Factor VIII and XII was proven. Conclusion(s): Cardiac manifestations are common and potentially life-threatening in MIS-C and should be assessed for at presenta-tion and during the clinical course as indicated.

BOOZE, BETAS, AND A FATTY SOLUTION TO SPARE PANDEMIC WOES

SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The COVID-19 pandemic raised economic strife, social isolation, fear from contagion, and anxiety to a level where 45% of surveyed U.S. adults report a detriment to their mental health. With U.S. suicide rates up from 10 to 14 cases per 100,000 over the past 20 years, the health and safety of a vulnerable mental health population becomes more of a concern. We report a case of an individual with depression who was resuscitated after severe toxicity from alcohol and beta-blocker ingestions. CASE PRESENTATION: A 58-year-old woman with prior suicide attempts was found in an obtunded state after finishing a 20-pack of beer and swallowing a propranolol 20 mg pill bottle. On admission, she presented with bradycardia, hypotension, and alteration to a Glasgow Coma Scale of 9 with emesis residue on her face. Her blood gas revealed an anion-gap metabolic acidosis with a pH of 7.26, lactate of 2.53, normal potassium and calcium, and glucose of 134 mg/dL. Toxicity labs were notable for an alcohol of 199 mg/dL. Her EKG demonstrated a junctional bradycardia with a p-wave complex after the QRS consistent with retrograde depolarization of the atrium (Image 1). She was intubated to protect her airway. She subsequently developed cardiac arrest secondary to pulseless electrical activity. She underwent CPR for 33 minutes with boluses of intravenous epinephrine, glucagon, insulin, calcium gluconate, and sodium bicarbonate prior to return of spontaneous circulation. Due to failure of transcutaneous pacing, a transvenous pacer was placed. In concert with Poison Control, she was started on an a euglycemic insulin drip and an intralipid infusion. Her hemodynamics improved, and she was weaned off pacing and ICU interventions within 24 hours. She was discharged a week after admission with no residual morbidities. DISCUSSION: Overdose from nonselective beta-blockers can result in bradycardia, hypotension, seizures, QRS widening, QTc prolongation with ventricular tachy-arrhythmias, hyperkalemia, and hypoglycemia. Understanding the pharmacodynamics of beta-blocker toxicity enables targeted interventions to improve: chronotropy with epinephrine, glucagon, and pacing;inotropy with insulin, calcium, glucagon, and phosphodiesterase inhibitors;QRS widening with sodium bicarbonate;and QTc prolongation with magnesium or lidocaine. The high lipid solubility of propanol allows for intravenous lipid infusions to aid in drug elimination for patients in refractory cardiogenic shock. CONCLUSIONS: Despite a lack of labs for monitoring beta blocker toxicity, our case demonstrates successful resuscitation in a severe overdose. Perhaps an absence of hyperkalemia, hypoglycemia, QRS and QTc changes, and tachy-arrhythmias in this incident portended to a decreased morbidity and mortality. Ultimately, we reaffirmed the role of intralipid infusions as a critical treatment adjunct for recovery from cardiogenic shock secondary to beta blockade. Reference #1: Sher L. The impact of the COVID-19 pandemic on suicide rates. QJM. 2020;113(10):707-712. Reference #2: Kerns W 2nd. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007;25(2):309-viii. Reference #3: Anderson AC. Management of beta-adrenergic blocker poisoning. Clin Pediatr Emerg Med. 2008;9(1):4–16. DISCLOSURES: No relevant relationships by Jackie Hayes No relevant relationships by Andrew Salomon

HYDROXYCHLOROQUINE OVERDOSE

SESSION TITLE: Cases of Overdose, OTC, and Illegal Drug Critical Cases Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Hydroxychloroquine (HCQ) is commonly prescribed for the management of connective tissue disorders such as systemic lupus erythematosus and rheumatoid arthritis. Despite its widespread use, there are limited case reports describing HCQ intoxication and management. HCQ toxicity presents predominantly with cardiovascular manifestations, including hypotension, arrhythmias, and QT interval prolongation on electrocardiogram (EKG). Other findings include visual disturbances, altered mental status, and hypokalemia. CASE PRESENTATION: We present the case of a 60-year-old female with a history of rheumatoid arthritis and depression. She presented to the emergency department (ED) after ingesting 10-15 tablets of HCQ 200 mg in a suicide attempt. In the ED, she was noted to be lethargic and tachycardic. EKG revealed sinus tachycardia with a heart rate of 127 beats per minute and prolonged QTc of 680msec. The diagnostic evaluation also revealed hypokalemia with potassium 3.7mmol/l. Initial management in the ED included administration of activated charcoal, potassium supplementation, and intravenous bicarbonate infusion. The patient was admitted to the ICU for monitoring and supportive care. Serum electrolyte panel and EKG were monitored. The patient made an uneventful recovery after 2-3 days. The QT interval normalized, and hypokalemia improved. She was subsequently discharged to an inpatient psychiatric unit. DISCUSSION: Although HQC is commonly prescribed, there is limited data describing overdose. Our case of HCQ overdose presented as changes in mental status, QT interval prolongation, and hypokalemia. Similar findings have been reported in previous case reports. Management includes early gastric decontamination with activated charcoal, potassium supplementation, and supportive care. Intravenous bicarbonate infusion has been utilized for prolonged QT intervals, and benzodiazepines have been used for agitation and sedation. CONCLUSIONS: Although rare, HCQ toxicity can be life-threatening. It is a commonly prescribed agent, and therefore the clinician should be aware of its toxicity profile and management. Reference #1: Bakhsh HT. Hydroxychloroquine Toxicity Management: A Literature Review in COVID-19 Era. J Microsc Ultrastruct. 2020;8(4):136-140. Published 2020 Dec 10. doi:10.4103/JMAU.JMAU_54_20 Reference #2: McKeever R. Chloroquine/hydroxychloroquine overdose. Vis J Emerg Med. 2020;21:100777. doi:10.1016/j.visj.2020.100777 Reference #3: Lebin JA, LeSaint KT. Brief Review of Chloroquine and Hydroxychloroquine Toxicity and Management. West J Emerg Med. 2020;21(4):760-763. Published 2020 Jun 3. doi:10.5811/westjem.2020.5.47810 DISCLOSURES: No relevant relationships by Priyaranjan Kata No relevant relationships by Wajahat Khan No relevant relationships by Pratiksha Singh

POST-COVID-19 ASPERGILLOSIS

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Since the start of Covid-19 pandemic, several respiratory microorganisms have been identified that cause coinfection with Sars-Cov-2. Bacteria like Staphylococcus aureus and viruses like influenza are some of the identified pathogens. Rarely, fungal infections from Aspergillus are also being reported. CASE PRESENTATION: 59-year-old male with past medical history of hypertension and hyperlipidemia was admitted for shortness of breath and was found to be positive for Covid-19. He received Remdesivir, dexamethasone & tocilizumab. He required non-invasive ventilation via continuous positive airway pressure but continued to remain hypoxemic with elevated procalcitonin, he was treated with cefepime for bacterial pneumonia. Patient required emergent intubation and eventually underwent tracheostomy. He developed methicillin-resistant Staphylococcus aureus pneumonia for which he received vancomycin. He was eventually discharged to long term acute care facility. Patient was readmitted after 2 months due to worsening respiratory status. Computed Tomography Angiography of chest was negative for pulmonary embolism but showed pleural effusion. He underwent thoracentesis which showed exudative effusion with negative cultures. Echocardiogram showed right heart failure. Patient's symptoms were believed to be due to Covid-19 fibrosis. He required home oxygen and also received pulmonary rehabilitation. One year after the initial Covid-19 infection, he developed pulmonary hypertension and was referred for lung transplant consultation. However, he developed severe hemoptysis requiring intubation and vasopressors. Galactomannan was positive, Karius digital culture revealed Aspergillus Niger for which he received voriconazole. He was not deemed a suitable candidate for lobectomy. Patient developed arrhythmia and had prolonged QT interval so voriconazole was switched to Isavuconazole. He continued to have hemoptysis and his condition did not improve so family requested to transition care and patient passed away. DISCUSSION: Several studies have proven co-infection of Aspergillus with Covid-19. This case highlights Aspergillus infection approximately 1 year after initial Covid-19 infection. Sars-Cov-2 causes damage to airway lining which can result in Aspergillus invading tissues. IL-6 is increased in severe Covid-19 infection. Tocilizumab is an anti-IL-6 receptor antibody that has been approved for treatment of Covid-19 pneumonia. However, IL-6 provides immunity against Aspergillus so use of tocilizumab decreases protection against Aspergillosis which is usually the reason for co-infection. However, in this case patient developed fungal infection later during Covid-19 fibrosis stage. CONCLUSIONS: Recognizing fungal etiology early on is important in Covid-19 patients as mortality is high and appropriate intervention can reduce morbidity and mortality. Some patient may eventually require lung resection. Reference #1: Kakamad FH, Mahmood SO, Rahim HM, Abdulla BA, Abdullah HO, Othman S, Mohammed SH, Kakamad SH, Mustafa SM, Salih AM. Post covid-19 invasive pulmonary Aspergillosis: a case report. International journal of surgery case reports. 2021 May 1;82:105865. Reference #2: Nasrullah A, Javed A, Malik K. Coronavirus Disease-Associated Pulmonary Aspergillosis: A Devastating Complication of COVID-19. Cureus. 2021 Jan 30;13(1). Reference #3: Dimopoulos G, Almyroudi MP, Myrianthefs P, Rello J. COVID-19-associated pulmonary aspergillosis (CAPA). Journal of Intensive Medicine. 2021 Oct 25;1(02):71-80. DISCLOSURES: No relevant relationships by Maria Haider Baig

Adverse Effects of Hydroxychloroquine in COVID-19 Patients- A Review of Eudravigilance Database: An International Journal of Medical Toxicology and Drug Experience

Introduction: Hydroxychloroquine is an antimalarial drug that belongs to the 4-aminoquinolone group [1]. Despite of this properties presents several immunomodulatory and anti-inflammatory characteristics [1,2]. In 2020, with the emergence of the COVID-19 pandemic, researchers used existing drugs with potential for the treatment of COVID-19, including hydroxychloroquine, which ended up being used off-label [3,4]. From the clinical trials hydroxychloroquine has many adverse effects that can increase risk for the SARS-COV-2 patients health. Common adverse effects are related to gastrointestinal and cardiovascular systems, neurotoxicity and retinopathy [2,5]. Objective: The objective of this research was to describe the adverse effects profile of hydroxychloroquine in COVID-19 patients and to characterize the risks associated with off-label use of hydroxychloroquine. Methods: An observational, retrospective and descriptive study was conducted. Information collected from the "Eudravigilance" database was analyzed using descriptive statistics with R Studio® software. Information about the source of reporting, patient sex, serious adverse reactions, deaths and off-label cases and their outcome, were evaluated and compared in the pre- and post-pandemic period. Results: The number of reports of adverse reactions to hydroxychloroquine increased significantly during the pandemic period (increase of 310.3%), with health professionals (92.0%) and woman (2020: 64%;2021: 81%) reporting the most. The analysis of age groups allowed us to conclude that the 18-64 age group has the highest number of reported patients (2020: 49%;2021: 53%). The offlabel use of hydroxychloroquine was also an important aspect to consider in this study: in the period of 2020-2021, a total of 29.8% of suspected ADR have been caused by hydroxychloroquine in off-label use, with an important percentage of those being associated with COVID utilization (20.0%). Finally, deaths associated with the use of hydroxychloroquine were also evaluated, of which 67.0% are described in off-label use. Conclusion: The number of reports of adverse reactions to hydroxychloroquine increased significantly during the pandemic. The potential for harm increased as off-label administration of hydroxychloroquine was associated with an increased incidence and severity of adverse reactions. However, associated with other drugs, this drug may potentiate certain adverse reactions, such as QT interval prolongation, nausea, dizziness, hypoglycaemia, heart failure, among others. Regarding outcomes, there seems to be an increase in the number of deaths associated with hydroxychloroquine, however causality has not been established for the observed data. Hydroxychloroquine presented varied adverse reactions in the observed data, and its off-label use during the pandemic showed an increase in its incidence.

Active Pharmacovigilance in COVID-19 Patients: The Role of a Clinical Pharmacist in the Reporting of Adverse Drug Events: An International Journal of Medical Toxicology and Drug Experience

Introduction: Like many countries in the world, the first wave of the COVID-19 (Coronavirus Disease 2019) pandemic in Morocco was marked by an overload of infected patients and unprecedented challenges. This, combined with the unknown nature of the disease, has compelled clinicians to prescribe a wide range of medicines, including experimental drugs as well as symptomatic therapies. These practices were associated with an increase in the incidence of adverse drug events (ADEs), which were reported to be higher in the COVID-19 population [1]. Among front-line health workers, pharmacists were assigned various roles such as active and passive pharmacovigilance in order to ensure the safe use of drugs [2]. This was the case of our hospital, where some pharmacists participate in medical rounds to provide pharmaceutical care near patients. Objective: To demonstrate the importance of a clinical pharmacist in the reporting of ADEs in hospitalized COVID-19 patients. Methods: An observational study was conducted between September 2020 and January 2021 at a university hospital in Rabat. Only one of five COVID-19 units had a pharmacist as a full time member of the medical team. The notification of ADEs are made on a sheet designed by the National Pharmacovigilance Center. After assessing the collected ADE's, the pharmacist compared them to all ADE's that were reported from other COVID-19 units during the study period. Data were subsequently analyzed using Excel. Results: A total of 42 ADEs in 35 patients were notified by the pharmacist (population size = 120). Experimental drugs used for the viral treatment (hydroxychloroquine and azithromycin) were the most commonly recorded medications with ADEs (30%), 27% were anti-coagulants and 13,5% were corticosteroids. Regarding ADEs, 26% consisted of QT interval prolongation, followed by hyperkalemia (26%), hyperglycemia (19%), bleeding (7%), and hepatic cytolysis (5%). In comparison, only 3 ADEs were notified from other COVID-19 units of the hospital. Conclusion: Results of our study suggests that the presence of a pharmacist in a multidisciplinary team is crucial to enhance patient care and safety, particularly in these times of crisis. Our study has also shed light on the poor reporting rate of ADEs in the hospitalized patients, which was previously mentioned to be common in the developing world [3]. Strategies to improve the pharmacovigilance system in Morocco are needed to better prepare healthcare structures for future epidemics.