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1.
Stem Cell Reports ; 17(3): 522-537, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1692862

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9cOE) identified concordantly up-regulated genes enriched into stress-related apoptosis and inflammation signaling pathways, and down-regulated CM functional genes. Proteomic analysis revealed enhanced expressions of apoptotic factors, whereas reduced protein factors for ATP synthesis by Orf9cOE. Orf9cOE significantly reduced cellular ATP level, induced apoptosis, and caused electrical dysfunctions of hPSC-CMs. Finally, drugs approved by the U.S. Food and Drug Administration, namely, ivermectin and meclizine, restored ATP levels and ameliorated CM death and functional abnormalities of Orf9cOE hPSC-CMs. Overall, we defined the molecular mechanisms underlying the detrimental impacts of Orf9c on hPSC-CMs and explored potentially therapeutic approaches to ameliorate Orf9c-induced cardiac injury and abnormalities.


Subject(s)
COVID-19/pathology , Coronavirus Nucleocapsid Proteins/genetics , Genome-Wide Association Study/methods , SARS-CoV-2/genetics , Action Potentials/drug effects , Adenosine Triphosphate/metabolism , Apoptosis/drug effects , Apoptosis/genetics , COVID-19/virology , Down-Regulation , Humans , Ivermectin/pharmacology , Meclizine/pharmacology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Phosphoproteins/genetics , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/metabolism , Protein Interaction Maps/genetics , RNA, Messenger/chemistry , RNA, Messenger/metabolism , SARS-CoV-2/isolation & purification , Signal Transduction/genetics , Transcriptome/drug effects , Up-Regulation
2.
Eur J Pharmacol ; 915: 174670, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1549763

ABSTRACT

Hydroxychloroquine (HCQ) is a derivative of the antimalaria drug chloroquine primarily prescribed for autoimmune diseases. Recent attempts to repurpose HCQ in the treatment of corona virus disease 2019 has raised concerns because of its propensity to prolong the QT-segment on the electrocardiogram, an effect associated with increased pro-arrhythmic risk. Since chirality can affect drug pharmacological properties, we have evaluated the functional effects of the R(-) and S(+) enantiomers of HCQ on six ion channels contributing to the cardiac action potential and on electrophysiological parameters of isolated Purkinje fibers. We found that R(-)HCQ and S(+)HCQ block human Kir2.1 and hERG potassium channels in the 1 µM-100 µM range with a 2-4 fold enantiomeric separation. NaV1.5 sodium currents and CaV1.2 calcium currents, as well as KV4.3 and KV7.1 potassium currents remained unaffected at up to 90 µM. In rabbit Purkinje fibers, R(-)HCQ prominently depolarized the membrane resting potential, inducing autogenic activity at 10 µM and 30 µM, while S(+)HCQ primarily increased the action potential duration, inducing occasional early afterdepolarization at these concentrations. These data suggest that both enantiomers of HCQ can alter cardiac tissue electrophysiology at concentrations above their plasmatic levels at therapeutic doses, and that chirality does not substantially influence their arrhythmogenic potential in vitro.


Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Heart/drug effects , Hydroxychloroquine/chemistry , Hydroxychloroquine/pharmacology , Ion Channels/drug effects , Action Potentials/drug effects , Animals , Arrhythmias, Cardiac/chemically induced , Electrocardiography , Electrophysiologic Techniques, Cardiac , Ether-A-Go-Go Potassium Channels , Humans , Membrane Potentials/drug effects , Patch-Clamp Techniques , Purkinje Fibers/drug effects , Rabbits , Stereoisomerism
3.
Eur J Pharmacol ; 913: 174632, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1509762

ABSTRACT

Chloroquine and hydroxychloroquine have been proposed recently as therapy for SARS-CoV-2-infected patients, but during 3 months of extensive use concerns were raised related to their clinical effectiveness and arrhythmogenic risk. Therefore, we estimated for these compounds several proarrhythmogenic risk predictors according to the Comprehensive in vitro Proarrhythmia Assay (CiPA) paradigm. Experiments were performed with either CytoPatch™2 automated or manual patch-clamp setups on HEK293T cells stably or transiently transfected with hERG1, hNav1.5, hKir2.1, hKv7.1+hMinK, and on Pluricyte® cardiomyocytes (Ncardia), using physiological solutions. Dose-response plots of hERG1 inhibition fitted with Hill functions yielded IC50 values in the low micromolar range for both compounds. We found hyperpolarizing shifts of tens of mV, larger for chloroquine, in the voltage-dependent activation but not inactivation, as well as a voltage-dependent block of hERG current, larger at positive potentials. We also found inhibitory effects on peak and late INa and on IK1, with IC50 of tens of µM and larger for chloroquine. The two compounds, tested on Pluricyte® cardiomyocytes using the ß-escin-perforated method, inhibited IKr, ICaL, INa peak, but had no effect on If. In current-clamp they caused action potential prolongation. Our data and those from literature for Ito were used to compute proarrhythmogenic risk predictors Bnet (Mistry HB, 2018) and Qnet (Dutta S et al., 2017), with hERG1 blocking/unblocking rates estimated from time constants of fractional block. Although the two antimalarials are successfully used in autoimmune diseases, and chloroquine may be effective in atrial fibrillation, assays place these drugs in the intermediate proarrhythmogenic risk group.


Subject(s)
Antiviral Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Chloroquine/pharmacology , Hydroxychloroquine/adverse effects , Action Potentials/drug effects , Biological Assay , COVID-19/drug therapy , Computer Simulation , Correlation of Data , Dose-Response Relationship, Drug , ERG1 Potassium Channel/agonists , ERG1 Potassium Channel/antagonists & inhibitors , ERG1 Potassium Channel/metabolism , HEK293 Cells , Humans , Inhibitory Concentration 50 , KCNQ1 Potassium Channel/antagonists & inhibitors , KCNQ1 Potassium Channel/metabolism , Kinetics , Myocytes, Cardiac/drug effects , NAV1.5 Voltage-Gated Sodium Channel/metabolism , Patch-Clamp Techniques , Potassium Channels, Inwardly Rectifying/antagonists & inhibitors , Potassium Channels, Inwardly Rectifying/metabolism , Potassium Channels, Voltage-Gated/metabolism , Risk Assessment , SARS-CoV-2/drug effects
6.
Europace ; 23(1): 123-129, 2021 01 27.
Article in English | MEDLINE | ID: covidwho-1387869

ABSTRACT

AIMS: The main severe complications of SARS-CoV-2 infection are pneumonia and respiratory distress syndrome. Recent studies, however, reported that cardiac injury, as assessed by troponin levels, is associated with a worse outcome in these patients. No study hitherto assessed whether the simple standard electrocardiogram (ECG) may be helpful for risk stratification in these patients. METHODS AND RESULTS: We studied 324 consecutive patients admitted to our Emergency Department with a confirmed diagnosis of SARS-CoV-2 infection. Standard 12-lead ECG recorded on admission was assessed for cardiac rhythm and rate, atrioventricular and intraventricular conduction, abnormal Q/QS wave, ST segment and T wave changes, corrected QT interval, and tachyarrhythmias. At a mean follow-up of 31 ± 11 days, 44 deaths occurred (13.6%). Most ECG variables were significantly associated with mortality, including atrial fibrillation (P = 0.002), increasing heart rate (P = 0.002), presence of left bundle branch block (LBBB; P < 0.001), QRS duration (P <0 .001), a QRS duration of ≥110 ms (P < 0.001), ST segment depression (P < 0.001), abnormal Q/QS wave (P = 0.034), premature ventricular complexes (PVCs; P = 0.051), and presence of any ECG abnormality [hazard ratio (HR) 4.58; 95% confidence interval (CI) 2.40-8.76; P < 0.001]. At multivariable analysis, QRS duration (P = 0.002), QRS duration ≥110 ms (P = 0.03), LBBB (P = 0.014) and presence of any ECG abnormality (P = 0.04) maintained a significant independent association with mortality. CONCLUSION: Our data show that standard ECG can be helpful for an initial risk stratification of patients admitted for SARS-CoV-2 infectious disease.


Subject(s)
COVID-19/complications , Electrocardiography , Heart Conduction System/physiopathology , Heart Diseases/diagnosis , Heart Rate , Action Potentials , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Female , Heart Diseases/etiology , Heart Diseases/mortality , Heart Diseases/physiopathology , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors , Time Factors
7.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363681

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
8.
Europace ; 23(3): 345-352, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1343692

ABSTRACT

During the coronavirus 2019 (COVID-19) pandemic, outpatient visits in the atrial fibrillation (AF) clinic of the Maastricht University Medical Centre (MUMC+) were transferred into teleconsultations. The aim was to develop anon-demand app-based heart rate and rhythm monitoring infrastructure to allow appropriatmanagement of AF through teleconsultation. In line with the fundamental aspects of integrated care, including actively involving patients in the care process and providing comprehensive care by a multidisciplinary team, we implemented a mobile health (mHealth) intervention to support teleconsultations with AF patients: TeleCheck-AF. The TeleCheck-AF approach guarantees the continuity of comprehensive AF management and supports integrated care through teleconsultation during COVID-19. It incorporates three important components: (i) a structured teleconsultation ('Tele'), (ii) a CE-marked app-based on-demand heart rate and rhythm monitoring infrastructure ('Check'), and (iii) comprehensive AF management ('AF'). In this article, we describe the components and implementation of the TeleCheck-AF approach in an integrated and specialized AF-clinic through teleconsultation. The TeleCheck-AF approach is currently implemented in numerous European centres during COVID-19.


Subject(s)
Atrial Fibrillation/diagnosis , COVID-19 , Heart Conduction System/physiopathology , Heart Rate , Mobile Applications , Remote Consultation/instrumentation , Smartphone , Action Potentials , Atrial Fibrillation/physiopathology , Atrial Fibrillation/therapy , Delivery of Health Care, Integrated , Humans , Predictive Value of Tests , Reproducibility of Results
9.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1258081

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
10.
Cardiovasc Toxicol ; 21(9): 687-694, 2021 09.
Article in English | MEDLINE | ID: covidwho-1237553

ABSTRACT

Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another "safer" therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Arrhythmias, Cardiac/diagnosis , Breast Neoplasms/drug therapy , COVID-19/drug therapy , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Electrocardiography , Estrogen Antagonists/adverse effects , Heart Conduction System/drug effects , Tamoxifen/adverse effects , Action Potentials , Anti-Bacterial Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , COVID-19/complications , COVID-19/diagnosis , Drug Substitution , Female , Heart Conduction System/physiopathology , Heart Rate/drug effects , Humans , Middle Aged , Predictive Value of Tests , Risk Assessment , Risk Factors
11.
Bull Exp Biol Med ; 170(5): 649-653, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1159147

ABSTRACT

Ivermectin (IVM) belongs to the class of macrocyclic lactones, which is used as an antiparasitic agent. At present, the researchers focus on possibility to use IVM in treatment of certain forms of cancer and viral diseases such as COVID-19. The mechanisms of IVM action are not clear. It is assumed that IVM affects chloride channels and increases cytoplasmic concentration of chloride. This study examines the effect of IVM on chloride currents induced by glycine (IGly). Experiments were carried out on isolated pyramidal neurons of the rat hippocampus with whole-cell patch clamp. A short-term (600 msec) application of IVM in a concentration of 10 µM induced a slow inward current, which persisted after washing the neurons. The low concentrations (0.1-1000 nM) of IVM did not induce any novel current, but it rapidly and reversibly reduced the peak amplitude and accelerated desensitization of IGly in a dose-dependent manner. The threshold concentrations of IVM sufficient to reduce peak amplitude of IGly and to accelerate desensitization of IGly were 100 nM and 0.1 nM, respectively. The study revealed a high sensitivity of neuronal glycine receptors to IVM.


Subject(s)
Chloride Channels/drug effects , Glycine/pharmacology , Ivermectin/pharmacology , Pyramidal Cells/drug effects , Action Potentials/drug effects , Animals , Antiviral Agents/pharmacology , Cells, Cultured , Chloride Channels/metabolism , Dose-Response Relationship, Drug , Hippocampus/cytology , Hippocampus/metabolism , Ion Channel Gating/drug effects , Patch-Clamp Techniques , Pyramidal Cells/physiology , Rats , Rats, Wistar , Receptors, Glycine/drug effects , Receptors, Glycine/metabolism
12.
J Cardiovasc Med (Hagerstown) ; 22(3): 197-203, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1133865

ABSTRACT

AIM: The aim of the current study was to evaluate P-wave dispersion (PWD) as a predictor of atrial fibrillation in patients with newly diagnosed COVID-19. In addition, the relationship between the PWD and inflammation parameters was investigated. METHODS: A total of 140 newly diagnosed COVID-19 patients and 140 age- and sex-matched healthy individuals were included in the study. The risk of atrial fibrillation was evaluated by calculating the electrocardiographic PWD. C-reactive protein (CRP), white blood cell, neutrophil and neutrophil-to-lymphocyte ratio (NLR) were measured in patients with newly diagnosed COVID-19. RESULTS: PWD, white blood cell, NLR and CRP levels were significantly higher in the COVID-19 group than the control group. There was a significant positive correlation between PWD and CRP level (rs = 0.510, P < 0.001) and NLR in COVID-19 group (rs = 0.302, P = 0.001). In their follow-up, 13 (9.3%) patients, 11 of whom were in the ICU, developed new atrial fibrillation. CONCLUSION: Our study showed for the first time in literature that the PWD, evaluated electrocardiographically in patients with newly diagnosed COVID-19, was prolonged compared with normal healthy individuals. A positive correlation was found between PWD, CRP level and NLR. We believe that pretreatment evaluation of PWD in patients with newly diagnosed COVID-19 would be beneficial for predicting atrial fibrillation risk.


Subject(s)
Action Potentials , Atrial Fibrillation/etiology , COVID-19/diagnosis , Electrocardiography , Heart Conduction System/physiopathology , Heart Rate , Adult , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , Cross-Sectional Studies , Female , Humans , Lymphocyte Count , Lymphocytes , Male , Middle Aged , Neutrophils , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors
13.
Neurophysiol Clin ; 51(2): 183-191, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1087170

ABSTRACT

OBJECTIVE: To assess whether patients with acute inflammatory demyelinating polyneuropathy (AIDP) associated with SARS-CoV-2 show characteristic electrophysiological features. METHODS: Clinical and electrophysiological findings of 24 patients with SARS-CoV-2 infection and AIDP (S-AIDP) and of 48 control AIDP (C-AIDP) without SARS-CoV-2 infection were compared. RESULTS: S-AIDP patients more frequently developed respiratory failure (83.3% vs. 25%, P=0.000) and required intensive care unit (ICU) hospitalization (58.3% vs. 31.3%, P=0.000). In C-AIDP, distal motor latencies (DMLs) were more frequently prolonged (70.9% vs. 26.2%, P=0.000) whereas in S-AIDP distal compound muscle action potential (dCMAP) durations were more frequently increased (49.5% vs. 32.4%, P=0.002) and F waves were more often absent (45.6% vs. 31.8%, P=0.011). Presence of nerves with increased dCMAP duration and normal or slightly prolonged DML was elevenfold higher in S-AIDP (31.1% vs. 2.8%, P=0.000);11 S-AIDP patients showed this pattern in 2 nerves. CONCLUSION: Increased dCMAP duration, thought to be a marker of acquired demyelination, can also be oserved in critical illness myopathy. In S-AIDP patients, an increased dCMAP duration dissociated from prolonged DML, suggests additional muscle fiber conduction slowing, possibly due to a COVID-19-related hyperinflammatory state. Absent F waves, at least in some S-AIDP patients, may reflect α-motor neuron hypoexcitability because of immobilization during the ICU stay. These features should be considered in the electrodiagnosis of SARS-CoV-2 patients with weakness, to avoid misdiagnosis.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Guillain-Barre Syndrome/etiology , Guillain-Barre Syndrome/physiopathology , Action Potentials , Adult , Aged , Aged, 80 and over , Critical Care/statistics & numerical data , Electrodiagnosis , Electrophysiological Phenomena , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Motor Neurons , Muscle, Skeletal/physiopathology , Neural Conduction , Respiratory Insufficiency/etiology , Sensory Receptor Cells
14.
Med Hypotheses ; 149: 110545, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1087149

ABSTRACT

The COVID-19 pandemic has become a burden to the global healthcare community. Despite the severity of the complications associated with COVID-19, no antiviral agent is yet available for the treatment of this disease. Several studies have reported arrhythmias as one of the numerous manifestations associated with COVID-19 infection. Clinicians use different therapeutic agents in the management of COVID-19 patients with arrhythmias, apart from ranolazine; however, some of these drugs are administered with caution because of their significant side effects. In this study, we reviewed the potential antiarrhythmic effects of ranolazine in the management of cardiac arrhythmias associated with COVID-19. Ranolazine is a second-line drug approved for the treatment of chronic stable angina pectoris. Previous studies have shown that ranolazine produces its beneficial cardiac effects without any significant impact on the body's hemodynamics; hence, blood pressure is not altered. Due to its reduced side effects, ranolazine may be more effective than other drugs in producing the desired relief from COVID-19 related arrhythmias, since it produces its antiarrhythmic effect by modulating sodium, potassium and calcium channels, and suppressing cytokine expression.


Subject(s)
Arrhythmias, Cardiac/complications , COVID-19/complications , COVID-19/drug therapy , Ranolazine/therapeutic use , Action Potentials , Angina, Stable/complications , Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/prevention & control , Cytokines/metabolism , Hemodynamics , Humans , Inflammation , Potassium Channels/metabolism , Sodium Channel Blockers/therapeutic use
16.
Europace ; 23(3): 451-455, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-1024096

ABSTRACT

AIMS: The novel coronavirus SARS-CoV-2 has shown the potential to significantly affect the cardiovascular system. Cardiac arrhythmias are commonly reported complications in COVID-19 hospitalized patients. METHODS AND RESULTS: While tachyarrhythmias seem most common, we describe four cases of COVID-19 patients who developed a transient high-degree atrioventricular (AV) block during the course of their hospitalization. All four patients who developed a high-degree AV block during their hospitalization with COVID-19 did not require permanent pacing. CONCLUSION: Similarly to most AV blocks associated with infectious organisms and given its transient nature, this case series suggests that conservative management strategies should be preferred in COVID-19 patients who develop complete heart block.


Subject(s)
Atrioventricular Block/etiology , Atrioventricular Node/physiopathology , COVID-19/complications , Heart Rate , Hospitalization , Action Potentials , Adult , Atrioventricular Block/diagnosis , Atrioventricular Block/physiopathology , Atrioventricular Block/therapy , COVID-19/diagnosis , COVID-19/therapy , Conservative Treatment , Electrocardiography , Female , Humans , Male , Middle Aged , Risk Factors , Treatment Outcome
17.
J Neurol Sci ; 420: 117271, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-1023663

ABSTRACT

More than half of patients who recover from COVID-19 experience fatigue. We studied fatigue using neuropsychological and neurophysiological investigations in post-COVID-19 patients and healthy subjects. Neuropsychological assessment included: Fatigue Severity Scale (FSS), Fatigue Rating Scale, Beck Depression Inventory, Apathy Evaluation Scale, cognitive tests, and computerized tasks. Neurophysiological examination was assessed before (PRE) and 2 min after (POST) a 1-min fatiguing isometric pinching task and included: maximum compound muscle action potential (CMAP) amplitude in first dorsal interosseous muscle (FDI) following ulnar nerve stimulation, resting motor threshold, motor evoked potential (MEP) amplitude and silent period (SP) duration in right FDI following transcranial magnetic stimulation of the left motor cortex. Maximum pinch strength was measured. Perceived exertion was assessed with the Borg-Category-Ratio scale. Patients manifested fatigue, apathy, executive deficits, impaired cognitive control, and reduction in global cognition. Perceived exertion was higher in patients. CMAP and MEP were smaller in patients both PRE and POST. CMAP did not change in either group from PRE to POST, while MEP amplitudes declined in controls POST. SP duration did not differ between groups PRE, increased in controls but decreased in patients POST. Patients' change of SP duration from PRE to POST was negatively correlated to FSS. Abnormal SP shortening and lack of MEP depression concur with a reduction in post-exhaustion corticomotor inhibition, suggesting a possible GABAB-ergic dysfunction. This impairment might be related to the neuropsychological alterations. COVID-19-associated inflammation might lead to GABAergic impairment, possibly representing the basis of fatigue and explaining apathy and executive deficits.


Subject(s)
Action Potentials/physiology , COVID-19/complications , Executive Function/physiology , Fatigue/virology , Muscle, Skeletal/physiopathology , Aged , Aged, 80 and over , COVID-19/physiopathology , COVID-19/psychology , Evoked Potentials, Motor/physiology , Fatigue/physiopathology , Fatigue/psychology , Female , Humans , Male , Middle Aged , Motor Cortex/physiopathology , Neuropsychological Tests , Transcranial Magnetic Stimulation
19.
BMB Rep ; 53(10): 545-550, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-979311

ABSTRACT

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cellderived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs. [BMB Reports 2020; 53(10): 545-550].


Subject(s)
Azithromycin/adverse effects , Cardiotoxicity/etiology , Chloroquine/adverse effects , Embryonic Stem Cells/drug effects , Myocytes, Cardiac/drug effects , Action Potentials , Animals , Arrhythmias, Cardiac/chemically induced , Azithromycin/administration & dosage , COVID-19 , Cell Differentiation , Chloroquine/administration & dosage , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Humans , Mice , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy
20.
Circ Arrhythm Electrophysiol ; 13(11): e008920, 2020 11.
Article in English | MEDLINE | ID: covidwho-975764

ABSTRACT

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias. However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality. METHODS: We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block. RESULTS: Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88). The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event. CONCLUSIONS: Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.


Subject(s)
Arrhythmias, Cardiac/epidemiology , COVID-19/epidemiology , Heart Conduction System/physiopathology , Heart Rate , Action Potentials , Adult , Aged , Aged, 80 and over , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/physiopathology , COVID-19/diagnosis , COVID-19/mortality , COVID-19/physiopathology , Female , Hospital Mortality , Hospitalization , Humans , Incidence , Male , Middle Aged , New York City/epidemiology , Prognosis , Registries , Risk Assessment , Risk Factors , Time Factors , Young Adult
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