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1.
Anti-Infective Agents ; 21(1):24-38, 2023.
Article in English | EMBASE | ID: covidwho-2215038

ABSTRACT

Coronavirus disease (COVID-19) is a pandemic disease caused by SARS-COV-2 that primarily attacks the respiratory system of the host. This disease was first reported in early December 2019, and the World Health Organization (WHO) classified the ongoing COVID-19 outbreak as a pandemic disease-causing global public health emergency by mid-January 2020. The human-to-human transmission occurs by droplets, infected hands, or surfaces with an in-cubation time of 2-14 days. It displays signs and symptoms, and if the disease progresses, it leads to death. To avoid symptomatic symptoms or increase infection severity, early diagnosis, quarantine, and supportive care can help to cure the patient infected with COVID-19. Several attempts have been projected for the development of vaccines against COVID-19. As of July 2, 2021, 600 vaccine candidates worldwide were evaluated against SARS-CoV-2, of which 300 have reached the preclinical stage of their development. Presently, Moderna (mRNA-1273), Shenzhen Geno-Immune Medical Institute (LV-SMENP-DC), Shenzhen Geno-Immune Medical Institute (Pathogen specific APC), CanSino Biologicals (Ad5-nCoV), Inovio Pharmaceuti-cals (INO-4800) have plunged into the phase I/II clinical trials (Source: ClinicalTrials.gov web-site;WHO). Scientists are increasingly seeking a key hide behind pathogenic pathways, epide-miological features, and future drug goals, which will lead to the development of successful strategies for prevention and treatment. Based on the current published data, we summarize the structure, life cycle of SARS-CoV-2 and the various product categories available as anti-COVID-19 agents (antiviral), with special emphasis on Chinese herbal medicines, which were licensed as anti-COVID agents by the Chinese Government. Such knowledge can be used as guidelines for COVID-19 clinical therapy. Copyright © 2023 Bentham Science Publishers.

2.
Journal of Pharmaceutical Negative Results ; 13:6927-6942, 2022.
Article in English | EMBASE | ID: covidwho-2206807

ABSTRACT

Cardiovascular inclusion has been accounted for in patients with serious intense respiratory condition Covid 2 contamination, which might be reflected by electrocardiographic changes. Cardiovascular injury is additionally connected with humanity, need for intensive care, and seriousness of illness in patients due to Coronavirus. Some case features cardiovascular contribution as an intricacy related with Coronavirus, even without indications and indications of interstitial pneumonia. Two Coronavirus incidents in our report displayed diverse ECG indications by means of the sickness caused decay. The main case introduced brief SI QIII TIII sound structure followed by changeable almost whole atrioventricular square, and the second exhibited ST-section height joined by choroidal ventricular tachycardiac. The hidden systems of these ECGs irregularities in the serious phase of Coronavirus might be ascribed to hypoxia and incendiary harm brought about by the infection. Since the scourge of Coronavirus pulled in the consideration, hearsays were encompassing ECG variations in the contaminated people. We pointed toward indicative dissimilar noticed ECG discoveries and talking about their experimental importance. This deliberate audit recommends that recognizing ECG designs that may be connected with Coronavirus is fundamental. Given that doctors don't perceive these examples, they may mistakenly hazard the existences of their patients. Moreover, significant medication instigated ECG changes give attention to the medical care laborers on the dangers of potential treatments. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

3.
Progress in Microbes and Molecular Biology ; 5(1), 2022.
Article in English | Scopus | ID: covidwho-2206363

ABSTRACT

Chemotherapeutics and biotherapeutics agents have been explored as a potential treatment for COVID-19. This study was aimed to elucidate latest update related to biotherapeutics and chemotherapeutics against COVID-19 and its variants as well as the product specifications and marketing dynamics of its pharmacotherapies. There are several chemotherapeutics that have been studied for the treatment of COVID-19, including Paxlovid (Nirmatrelvir & Ritonavir) fixed dose combination, nirmatrelvir and ritonavir fixed dose combination, Remdesivir (Vekulary/Covifor) fixed dose combination, chloroquine and hydroxychloroquine, molnupiravir, favipiravir, Infliximab (Remsima®) fixed dose combination tocilizumab (Actimera), casirivimab+imdevimab (Ronapreve) fixed dose combination, ivermectin, methylprednisole. These drugs have been repurposed for use in COVID-19 due to their antiviral properties and ability to reduce inflammation. The COVID-19 death cases have significantly reduced because of tested efficacy of advanced biotherapeutics and chemotherapeutics. As for marketing dynamics, the demand for chemotherapeutics for the treatment of COVID-19 has increased significantly since the outbreak of the pandemic. Hence, the prices of anti-viral and monoclonal antibodies in top COVID-19 affected countries is also presented here. Considering the molecular interactions, therapeutic activity, efficacy, and adverse effects, the USFDA and the WHO recommended the aforementioned drugs. The chances of approval seems favouring biotherapeutics as these have the best characteristics among the chemotherapeutics. Overall, this review contributes to the scientific understanding of the COVID-19. This can help to inform future research and development efforts and contribute to the overall advancement of knowledge in the field of medicine. © 2022, HH Publisher. All rights reserved.

4.
Desalination and Water Treatment ; 277:85-89, 2022.
Article in English | Scopus | ID: covidwho-2202483

ABSTRACT

Chloroquine has been adopted in some countries such as Brazil as a Covid-19 prevention proto-col;consequently, chloroquine has contaminated water resources in large quantities. In response to this menace, an adsorbent material from animal bone was used to remove chloroquine from contaminated water. Notably, no drug adsorption studies have been conducted in the past. The adsorbent was characterized by scanning electron microscopy and zeta potential measurements that exhibited favorable characteristics for the adsorbent. In this study, it was determined that the optimal mass of the adsorbent was 0.02 g at pH 7. The kinetic study demonstrated that 300 min was sufficient to reach equilibrium, and the best fit was pseudo-second-order. The adsorption isotherms were fitted in the Langmuir model, obtaining a maximum adsorp-tion capacity of 77.60 mg–1 at a temperature of 298 K. The thermodynamic parameters demonstrated a spontaneous, exothermic, and reversible process. Briefly, the adsorbent used had the potential to remove emerging pollutants from the environment. © 2022 Desalination Publications. All rights reserved.

5.
J Interferon Cytokine Res ; 43(1):35-42, 2023.
Article in English | PubMed | ID: covidwho-2188096

ABSTRACT

The human beta-coronavirus strain, OC43, provides a useful model for testing the antiviral activity of various agents. We compared the activity of several antiviral drugs against OC43, including remdesivir, chloroquine, interferon (IFN)-β, IFN-λ1, and IFN-λ4, in two distinct cell types: human colorectal carcinoma cell line (HCT-8 cells) and normal human bronchial epithelial (NHBE) cells. We also tested whether these agents mediate additive, synergistic, or antagonistic activity against OC43 infection when used in combination. When used as single agents, remdesivir exhibited stronger antiviral activity than chloroquine, and IFN-β exhibited stronger activity than IFN-λ1 or IFN-λ4 against OC43 in both HCT-8 and NHBE cells. Anakinra (IL-1 inhibitor) and tocilizumab (IL-6 inhibitor) did not mediate any antiviral activity. The combination of IFN-β plus chloroquine or remdesivir resulted in higher synergy scores and higher expression of IFN-stimulated genes than did IFN-β alone. In contrast, the combination of remdesivir plus chloroquine resulted in an antagonistic interaction in NHBE cells. Our findings indicate that the combined use of IFN-β plus remdesivir or chloroquine induces maximal antiviral activity against human coronavirus strain OC43 in primary human respiratory epithelial cells. Furthermore, our experimental OC43 virus infection model provides an excellent method for evaluating the biological activity of antiviral drugs.

7.
Pakistan Armed Forces Medical Journal ; 72(5):1752-1756, 2022.
Article in English | Scopus | ID: covidwho-2146765

ABSTRACT

Objective: To compare different treatment strategies for patients of COVID-19 in Pakistan. Study Design: Retrospective longitudinal study. Place and Duration of Study: Abbas Medical Hospital, Muzaffarabad Pakistan, during Apr 2021. Methodology: One hundred and twenty, COVID-19-positive patients between 31-45 years of age were admitted to Abbas hospital after carrying out the rRT-PCR test. Group-A was administered Azithromycin, while Group-B was treated with Azithromycin in combination with Hydroxychloroquine. Group-C was given a combination of oral Ivermectin and Doxycy-cline, and Group-D was treated with Lopinavir. Diagnostic tests include rRT-PCR, blood parameters such as creatinine, random blood sugar, alanine aminotransferase, complete blood count, ECG, chest x-ray and blood biomarkers including procalcitonin, C-reactive protein, lactate dehydrogenase and ferritin were performed at Day 1, 5, 7, 14 and 30. Results: Patients treated with Azithromycin revealed the highest recovery of about (77.80%) among COVID-19 patients, followed by the combination of Azithromycin and Hydroxychloroquine which was (65.56%), the combination of Ivermectin and Doxycycline was (19.63%), and Lopinavir was (9.06%) displayed minimum potency in recovering the COVID-19 positive patients (p-value <0.001). Conclusions: Azithromycin was most effective in helping patients recover from COVID-19, followed by a combination of azithromycin and Hydroxychloroquine. Patients who recovered after treatment with Ivermectin Doxycycline were lower, followed by those who recovered with Lopinavir only. © 2022, Army Medical College. All rights reserved.

8.
J Clin Med ; 11(22)2022 Nov 21.
Article in English | MEDLINE | ID: covidwho-2116118

ABSTRACT

The ongoing chronic use of hydroxychloroquine or chloroquine (HCQ/CQ) in rheumatic patients might impact their outcomes after a SARS-CoV-2 infection. Therefore, we sought to assess the mortality in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection through a comparison between individuals chronically using HCQ/CQ with those not taking these drugs. We performed a systematic review and meta-analysis of studies on PubMed, Embase, and Cochrane Central. We included full-length reports, prospective observational cohorts, and clinical trials of adult patients (aged ≥ 18 years) who were diagnosed with a COVID-19 infection. Case studies, case series, letters, comments, and editorials were excluded. The main outcome was all-cause mortality. This study is registered with PROSPERO (CRD42022341678). We identified 541 studies, of which 20 studies were included, comprising 236,997 patients. All-cause mortality was significantly lower in patients with prior chronic use of HCQ/CQ compared to those with no previous usage (OR 0.76; 95% CI 0.62-0.94; p = 0.01). There was a considerably lower incidence of hospitalization among patients with chronic HCQ/CQ use compared to their counterparts without HCQ/CQ usage (OR 0.80; 95% CI 0.65-0.99; p = 0.04). All-cause mortality and hospitalization were significantly lower in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection.

9.
J Exp Pharmacol ; 14: 353-365, 2022.
Article in English | MEDLINE | ID: covidwho-2114450

ABSTRACT

Introduction: Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ) are successfully deployed for different diseases beyond the prophylaxis and treatment of malaria. Both substances exhibit antiviral properties and have been proposed for prophylaxis and treatment of COVID-19 caused by SARS-CoV-2. CQ and HCQ cause similar adverse events including life-threatening cardiac arrhythmia generally based on QT-prolongation, which is one of the most reported adverse events for both agents associated with the treatment of COVID-19. Various drugs known to induce QT-prolongation have been proven to exert local anesthetic (LA)-like properties regarding their impact on the cardiac Na+ channel Nav1.5. Inhibition of Nav1.5 is considered as the primary mechanism of cardiotoxicity caused by LAs. However, the mechanism of the arrhythmogenic effects of CQ and HCQ related to Nav1.5 has not yet been fully investigated. Therefore, the exact mechanism of how CQ and HCQ affect the sodium currents generated by Nav1.5 need to be further elucidated. Objective: This in vitro study aims to investigate the effects of CQ and HCQ on Nav1.5-generated sodium currents to identify possible LA-like mechanisms that might contribute to their arrhythmogenic properties. Methods: The effects of CQ and HCQ on Nav1.5-generated sodium currents by HEK-293 cells expressing either wild-type human Nav1.5 or mutant Nav1.5 F1760A are measured using the whole-cell patch-clamp technique. Results: Both agents induce a state-dependent inhibition of Nav1.5. Furthermore, CQ and HCQ produce a use-dependent block of Nav1.5 and a shift of fast and slow inactivation. Results of experiments investigating the effect on the LA-insensitive mutant Nav1.5-F1760A indicate that both agents at least in part employ the proposed LA-binding site of Nav1.5 to induce inhibition. Conclusion: This study demonstrated that CQ and HCQ exert LA-typical effects on Nav1.5 involving the proposed LA binding site, thus contributing to their arrhythmogenic properties.

10.
Separation and Purification Technology ; 305:122517, 2023.
Article in English | ScienceDirect | ID: covidwho-2096024

ABSTRACT

Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel CN bond linked conjugated microporous polymers (CMPs) (BPT–DMB–CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent CN bond linked in the internal framework of BPT–DMB–CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich NH bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g−1), BPT–DMB–CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g−1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT–DMB–CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π − π, C  H···π interactions and size-matching effect in the CQP adsorption system on BPT–DMB–CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT–DMB–CMP. BPT–DMB–CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.

11.
Int J Antimicrob Agents ; 56(2): 106057, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-2095448

ABSTRACT

There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na+ and Ca2+ channels, background and voltage-dependent K+ channels, and pacemaker channels. The drugs also exert a vagolytic effect due at least in part to a muscarinic receptor antagonist action. They also interfere with normal autophagy flux, an effect that could aggravate ischaemia/reperfusion injury or post-infarct remodelling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.


Subject(s)
Chloroquine/adverse effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Betacoronavirus , COVID-19 , Chloroquine/therapeutic use , Humans , Pandemics , SARS-CoV-2
12.
Front Bioinform ; 1: 763540, 2021.
Article in English | MEDLINE | ID: covidwho-2089813

ABSTRACT

The ongoing COVID-19 outbreak have posed a significant threat to public health worldwide. Recently Toll-like receptor (TLR) has been proposed to be the drug target of SARS-CoV-2 treatment, the specificity and efficacy of such treatments remain unknown. In the present study we performed the investigation of repurposed drugs via a framework comprising of Search Tool for Interacting Chemicals (STITCH), Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking, and virus-host-drug interactome mapping. Chloroquine (CQ) and hydroxychloroquine (HCQ) were utilized as probes to explore the interaction network that is linked to SARS-CoV-2. 47 drug targets were shown to be overlapped with SARS-CoV-2 network and were enriched in TLR signaling pathway. Molecular docking analysis and molecular dynamics simulation determined the direct binding affinity of TLR9 to CQ and HCQ. Furthermore, we established SARS-CoV-2-human-drug protein interaction map and identified the axis of TLR9-ERC1-Nsp13 and TLR9-RIPK1-Nsp12. Therefore, the elucidation of the interactions of SARS-CoV-2 with TLR9 axis will not only provide pivotal insights into SARS-CoV-2 infection and pathogenesis but also improve the treatment against COVID-19.

13.
FEBS J ; 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2078462

ABSTRACT

Antiviral therapies are integral in the fight against SARS-CoV-2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID-19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post-translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN-COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post-translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti-inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID-19 infection. In this 'A Guide To' article, we provide an in-depth insight into the development of antiviral therapeutics against SARS-CoV-2 and their ability to help fight COVID-19.

14.
Journal of Pharmaceutical Negative Results ; 13:184-192, 2022.
Article in English | Web of Science | ID: covidwho-2072530

ABSTRACT

Background: The pathogenesis of SARS-CoV-2 is not fully understood, and currently there is currently no definitive drug or treatment against it. So, the drugs used to treat SARS-CoV-2 are mainly based on their effectiveness on previous species of coronaviruses. This review aimed to evaluate the studies performed on the use of the available drugs in the treatment of Covid-19 since the onset of this disease. Method: Comprehensive search strategy was conducted in the following databases: PubMed, Web of Science (IR) and Scopus, Psycinfo, Google Scholar, and national databases, including Scientific Information Database (SID) and Maglran from inception of Covid-19 to June 2022. Studies that reported the effect of different drugs in treatment of Covid-19 patients were included. Results: 38 studies (114,552 participants) were included in this systematic review study on used drug treatment of patients with Covid-19 including Remdesivir, HCQ & Chloroquine, Favipiravir, Molnupiravir, Arbidol, Kaletra, Oseltamivir, IVIG & Interferon. Conclusions: Remdesivir, HCQ & Chloroquine, Favipiravir, Molnupiravir, Arbidol, Kaletra, Oseltamivir, IVIG & Interferon are the most commonly used drugs in treatment of Covid-19. Although these drugs may be effective in improving the condition of Covid-19 patients in the inflammatory phase, the confirmation of their use requires more extensive clinical research.

15.
Journal of Scientometric Research ; 11(2):171-182, 2022.
Article in English | Web of Science | ID: covidwho-2072096

ABSTRACT

This study aims to present exploratory and descriptive research about Latin America's online information search and Twitter activity and the repercussions of chloroquine, hydroxychloroquine, and ivermectin, which were at the time considered promising alternatives to prevent or treat COVID-19. From the perspective of Webmetrics and Altmetrics -data were collected and analysed from Twitter around indexed outputs by titles with one of these three drugs and from Google Trends (Relative Search Interest) in Latin American countries. The results demonstrated that there might be parallels between Google Search and Twitter activity. The results also showed that ivermectin was, among the three selected drugs, the most searched in Google Search and higher activity on Latin America's Twitter accounts.

16.
Chest ; 162(4):A893, 2022.
Article in English | EMBASE | ID: covidwho-2060718

ABSTRACT

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

17.
Chest ; 162(4):A159, 2022.
Article in English | EMBASE | ID: covidwho-2060542

ABSTRACT

SESSION TITLE: The Cardiac Intensivist 2 SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Hydroxychloroquine and chloroquine are medications derived from aminoquinoline. They are disease-modifying antirheumatic drugs used in the treatment of systemic lupus erythematosus (SLE). Although well tolerated, they do have side effects such as retinopathy, vacuolar myopathy, neuropathy, and as seen in our patient, cardiotoxicity. CASE PRESENTATION: Patient is a 48 year old female with a past medical history significant for chronic kidney disease secondary to autosomal dominant polycystic kidney disease, SLE on hydroxychloroquine who presented to the emergency department complaining of weakness. On arrival the patient was found to be in cardiogenic shock. Her transthoracic echocardiogram revealed a reduced ejection fraction of 37% and a large pericardial effusion concerning for tamponade physiology. Her COVID-19 PCR test was positive. She was taken for emergent pericardiocentesis which revealed 300cc of exudative fluid. Patient’s right heart catheterization revealed mean pulmonary capillary wedge pressure of 23 mmHg, pulmonary artery pressures of 44 mmHg/24 mmHg, mean 31mmHg, cardiac index 1.1L/min/m² by thermodilution, 1.7 L/min/m² by Fick. Following right heart catheterization and intra aortic balloon pump placement, the patient was admitted to the medical intensive care unit (MICU) and placed on intravenous inotropic and vasopressor support. Shortly after arrival to the MICU, patient had an increase in vasopressor requirements. Bedside ultrasound revealed cardiac tamponade. Patient had approximately 400cc of bloody pericardial fluid removed from her pericardial drain. The decision was made for emergent venoarterial extracorporeal membrane oxygenation (ECMO) to be initiated. Endomyocardial biopsy was performed which revealed vacuolization in the cytoplasm of several myocytes as well as lymphocytes in the interstitium of the endocardium. The vacuoles found in the cardiac myocytes were PAS positive. These biopsy results are consistent with hydroxychloroquine cardiotoxicity. The patient’s hydroxychloroquine was discontinued. In addition to hemodynamic support, she also received intravenous immunoglobuluin and systemic steroids. After a prolonged hospitalization she was successfully discharged. DISCUSSION: Cardiotoxicity is a rare adverse reaction seen with hydroxychloroquine. A 2018 systematic review revealed 127 cases of cardiac toxicity associated with the use of hydroxychloroquine or chloroquine. Most patients had been treated with the medication for a prolonged period of time and the toxicity is dose dependent. The mechanism behind hydroxychloroquine and chloroquine induced cardiomyopathy is believed to be secondary to lysosomal dysfunction as a result of toxic phospholipid accumulation in cardiomyocytes. CONCLUSIONS: In patients with new onset cardiomyopathy, a detailed medication reconciliation should be conducted to evaluate for toxins such as hydroxychloroquine and chloroquine. Reference #1: Della Porta, A., Bornstein, K., Coye, A., Montrief, T., Long, B., & Parris, M. A. (2020). Acute chloroquine and hydroxychloroquine toxicity: A review for emergency clinicians. The American Journal of Emergency Medicine. Reference #2: Abbi, B., Patel, S., Kumthekar, A., Schwartz, D., & Blanco, I. (2020). A Case of Cardiomyopathy With Long-term Hydroxychloroquine Use. JCR: Journal of Clinical Rheumatology, 26(8), e300. Reference #3: Chatre, C., Roubille, F., Vernhet, H., Jorgensen, C., & Pers, Y. M. (2018). Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug safety, 41(10), 919-931. DISCLOSURES: no disclosure on file for Joseph Adams;no disclosure on file for Suliman Alradawi;No relevant relationships by George Kalapurakal No relevant relationships by Mohammed Siddiqui

18.
Front Cardiovasc Med ; 9: 844441, 2022.
Article in English | MEDLINE | ID: covidwho-2054984

ABSTRACT

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has emerged as a major cause of morbidity and mortality worldwide, placing unprecedented pressure on healthcare. Cardiomyopathy is described in patients with severe COVID-19 and increasing evidence suggests that cardiovascular involvement portends a high mortality. To facilitate fast development of antiviral interventions, drugs initially developed to treat other diseases are currently being repurposed as COVID-19 treatments. While it has been shown that SARS-CoV-2 invades cells through the angiotensin-converting enzyme 2 receptor (ACE2), the effect of drugs currently repurposed to treat COVID-19 on the heart requires further investigation. Methods: Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) were treated with five repurposed drugs (remdesivir, lopinavir/ritonavir, lopinavir/ritonavir/interferon beta (INF-ß), hydroxychloroquine, and chloroquine) and compared with DMSO controls. Transcriptional profiling was performed to identify global changes in gene expression programs. Results: RNA sequencing of hiPSC-CMs revealed significant changes in gene programs related to calcium handling and the endoplasmic reticulum stress response, most prominently for lopinavir/ritonavir and lopinavir/ritonavir/interferon-beta. The results of the differential gene expression analysis are available for interactive access at https://covid19drugs.jakobilab.org. Conclusion: Transcriptional profiling in hiPSC-CMs treated with COVID-19 drugs identified unfavorable changes with lopinavir/ritonavir and lopinavir/ritonavir/INF-ß in key cardiac gene programs that may negatively affect heart function.

19.
Curr Heart Fail Rep ; 19(6): 458-466, 2022 12.
Article in English | MEDLINE | ID: covidwho-2048548

ABSTRACT

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has popularized the usage of hydroxychloroquine and chloroquine (HCQ/CQ) as treatments for COVID-19. Previously used as anti-malarial and now commonly used in rheumatologic conditions, preliminary in vitro studies have demonstrated these medications also have anti-viral properties. Retinopathy and neuromyopathy are well recognized complications of using these treatments; however, cardiotoxicity is under-recognized. This review will discuss the implications and cardiotoxicity of HCQ/CQ, their mechanisms of action, and their utility in COVID-19. RECENT FINDINGS: Early clinical trials demonstrated a modest benefit of HCQ in COVID-19, causing a push for the usage of it. However, further large multi-center randomized control centers, demonstrated no benefit, and even a trend towards worse outcomes. The predominant cardiac complication observed with HCQ in COVID-19 was cardiac arrhythmias and prolonging of the QT interval. However, with chronic usage of HCQ/CQ, the development of heart failure (HF) and cardiomyopathy (CM) can occur. Although, most adverse cardiac events related to HCQ/CQ usage in COVID-19 were secondary to conduction disorders given the short duration of treatment, HCQ/CQ can cause CM and HF, with chronic usage. Given the insufficient evidence, HCQ/CQ usage in COVID-19 is not routinely recommended, especially with novel therapies now being developed and used. Additionally, usage of HCQ/CQ should prompt initial cardiac evaluation with ECG, and yearly monitoring, with consideration for advanced imaging if clinically warranted. The diagnosis of HCQ/CQ cardiomyopathy is important, as prompt cessation can allow for recovery when these changes are still reversible.


Subject(s)
COVID-19 , Heart Failure , Humans , Hydroxychloroquine/adverse effects , Pandemics , COVID-19/drug therapy , SARS-CoV-2 , Cardiotoxicity/etiology , Heart Failure/drug therapy , Chloroquine/adverse effects
20.
Researches and Applications of Artificial Intelligence to Mitigate Pandemics: History, Diagnostic Tools, Epidemiology, Healthcare, and Technology ; : 1-21, 2021.
Article in English | Scopus | ID: covidwho-2048814

ABSTRACT

This chapter reconnoiters various types of coronaviruses that cause zoonotic infection. Coronaviruses affecting the human population are known as human coronaviruses. Numerous coronaviruses exist that cause mild to severe ailments and fatalities, infection in the upper respiratory tract (URTI), acute respiratory syndrome, Middle East respiratory syndrome with varying degrees of severity may cause serious viral pneumonia, leading to hospitalization and death. SARS-CoV, transpired from China in late 2019, spread exponentially across the globe. World Health Organization stated this situation as a health emergency on March 11, 2020, and hence it was named as COVID-19. The outbreak of COVID-19 has affected health and economy around the world on an unprecedented scale. It is having a devastating effect on education, jobs, employment, domestic life, and the well-being of kids, youth, and elderly inhabitants. The incubation period for coronavirus disease is 2-14 days. Infected people have different clinical outcomes. However, people with preexisting cardiovascular disease, hypertension, diabetes, and related conditions have worse health suffering consequences. The transmission rate of COVID-19 is relatively high as compared to other viruses, researches have proposed many strategies in combating the virus contagious behavior;hand hygiene practice, physical distancing, limiting contact with other people, tracing contacts, disinfecting the surfaces, and wearing the proper mask are few to name. At the moment, no vaccines or drugs with proven efficacy are available for the medical management of COVID-19 patients. Chloroquine/hydroxychloroquine, Remdesivir, and Tocilizumab are strongly recommended treatment options in COVID-19. The chapter also throws light on coping strategies to overcome claustrophobia during the lock-down and dispelling COVID-19 rumors. © 2021 Elsevier Inc. All rights reserved.

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