{"id":37978,"date":"2021-03-30T12:00:25","date_gmt":"2021-03-30T12:00:25","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=37978"},"modified":"2021-08-02T11:36:19","modified_gmt":"2021-08-02T11:36:19","slug":"chloroquine-induced-prolonged-qt-interval-in-covid-19-patients-in-indonesia-case-series","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol14no1\/chloroquine-induced-prolonged-qt-interval-in-covid-19-patients-in-indonesia-case-series\/","title":{"rendered":"Chloroquine-induced Prolonged QT Interval in COVID-19 Patients in Indonesia: Case Series"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

Corona virus disease 2019 (COVID-19) pandemic, cause by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health concern1, 2<\/sup>. Currently no\u00a0specific treatment or vaccine are available against COVID-193-7<\/sup>, but chloroquine (CQ) or hydroxy chloroquine (HCQ) have been suggested as potential therapy of COVID-19based\u00a0on its anti-inflammatory and antiviral effect8-10<\/sup>.The mechanism of action of CQ or HCQ through its capability to decrease the expression of phosphatidylinositol binding\u00a0clathrin assembly protein (PICALM) could be valuable as aprophylactic candidate of COVID-19. Inhibition of PICALM expression, one of the three most abundant proteins in\u00a0clathrin-coated pits constrains SARS-CoV-2endocytosis into host cells11<\/sup>. Other mechanisms by which CQ against SARS-CoV-2 are acidic environment inside\u00a0lysosomes and late endosomes alteration, exosome release and phagolysosomal fusion, and host cytokine storm inhibition\u00a012<\/sup>. The limitation of CQ has been widely\u00a0published due to cardiotoxicity\u00a013<\/sup>, hepatotoxicity\u00a014<\/sup>,and hematotoxicity\u00a015<\/sup>. The common cardiac toxicities due toCQ are not well demarcated. The most common side effect of\u00a0CQ on the cardiac disturbance is prolonged QT interval (LQT), atrioventricular block (AV) block,and aprolonged QRS complex. LQT is the result of atypical repolarization of\u00a0the ventricular myocardium resulting in lengthening of the QT interval on the electrocardiogram. In females, the normal corrected QT interval is 430-440 milliseconds\u00a0(ms), with males slightly lower at 410-420 msand LQT when it is more than 500 ms16<\/sup>.<\/p>\n

There is no report of cardiac ischemia as the side effect of CQ against COVID-19. Long term use of CQ has reported causing coronary arterial disease among SLE patients17\u00a0<\/sup> but not in short term use.We describe two cases of COVID-19 at Sanjiwani Hospital of Bali, presented unusual manifestation of CQ side effect on the cardiac rhythm, a case\u00a0with ischemia at the anteroseptal lead of electro cardiography (ECG) while another case with usual CQ side LQT. This report warnsthe physician about the unusual\u00a0manifestation of CQ adverse effect and the importance of ECG monitoring during CQ treatment.<\/p>\n

Cases Report<\/strong><\/p>\n

Case 1<\/strong><\/p>\n

A 40-years-old woman presented with a chief complaint of cough and chest discomfort 12 days after contact with her husband, a positive COVID-19 patient. She experienced\u00a0mild headaches and fever two days prior admission to the hospital. She had a history of bronchitis and hemorrhoid and worked as a seller at the local art market. She did not\u00a0have any past medical history such as diabetes, hypertension, nor other comorbidities. Physical examination showed vital signs within normal limits, blood pressure of 120\/70\u00a0mmHg, heart rate 92x\/minute, respiratory rate 22x\/minute, temperature axilla of 37.3o<\/sup>C, and oxygen saturation of 98% in room air. All other examination revealed to be normal.<\/p>\n

Laboratory examination showed white blood cell 7.21×103<\/sup>\/\u03bcL, neutrophil 52.5% and lymphocyte 41.2%,hemoglobin 9.6 g\/dL with hematocrit 30.2% (MCV 68.3 and MCH\u00a021.7), thrombocyte 338×109<\/sup>\/L, random blood glucose of 89 mg\/dL, ureum 19.8 mg\/dL, creatinine serum 0.55 mg\/dL, sodium 141 mmol\/L, \u00a0potassium 3.3 mmol\/L and chloride\u00a0107 mmol\/L. Chest radiograph showed an increase in broncho-vascular marking in both lung fields. ECG showed normal sinus rhythm with a corrected QT interval (QTc)\u00a0interval of 459 ms (Fig.1A). The patient was diagnosed with positive COVID-19 by real-time polymerase chain reaction (RT-PCR) with mild hypochromic microcytic anemia due to iron deficiency. The patient then was treated with 500 mg of azithromycin once daily,\u00a0500 mg of chloroquine sulfate twice daily, and 75 mg of oseltamivir twice daily along with a high dose of vitamin C.<\/p>\n

On daily evaluation she appeared to be normal, her vital sign and physical examination within normal limit, cough disappear after 3 days of therapy. She kept complaining of\u00a0headaches and sleeping difficulty during the night. A counseling session with psychiatric was scheduled and she was diagnosed with mild anxiety. A daily dose of 0.5 mg\u00a0alprazolam was given with partial effect. On day 4th<\/sup>of therapy, she complained a frequent episode of nausea and vomiting followed by chest discomfort. An ECG was\u00a0performed, and showed normal sinus rhythm with an increased QTc interval to 510 ms (Fig.1B). The therapy of azithromycin, oseltamivir, and chloroquine was then halted,\u00a0and patient was put under close examination to an episode of cardiac abnormality. After four days of only supportive therapy, her QTc was returned to normal (Fig.1C). Her RT- PCR showed negative results two days later and she was then declared negative for COVID-19 after 10 days of hospital treatment and suggested to continue self-isolation at home.<\/p>\n

Case 2<\/strong><\/p>\n

A 51-years-old male presented to the emergency department with a sore throat after one-weekof contact with a confirmed COVID-19 patient. He did not have other signs of COVID-19 such as fever, cough, runny nose nor shortness of breath. He denied any\u00a0comorbidities such as diabetes, hypertension, nor other chronic illnesses. Physical examination revealed normal vital signs, normal heart, and lung sounds. Baseline ECG\u00a0was normal sinus rhythm (Fig.1D), white blood cell 15.55×103<\/sup>\/\u03bcL; absolute neutrophil count 7.16 x103<\/sup>\/\u03bcL and lymphocyte 6.02×103<\/sup>\/\u03bcL; hemoglobin 14.9 g\/dL with\u00a0hematocrit41.6% (MCV 85.8 and MCH 30.9). Thrombocyte 283×103<\/sup>\/\u03bcL, random blood glucose of 112 mg\/dL,ureum24.6 mg\/dL, creatinine serum 0.77 mg\/dL, sodium 142\u00a0mmol\/L; potassium 3.4 mmol\/L,chloride 104 mmol\/L, aspartate transaminase 24 U\/L, and alanine transaminase 34 U\/L. Chest radiograph, the revealed bronchovascular\u00a0patterns in both lungs. He was put on 500 mg of azithromycin once daily, 500 mg of chloroquine sulfate twice daily, and 75 mg of oseltamivir twice daily along with a high\u00a0dose of vitamin C on admission. On the day 3rd<\/sup>of CQ treatment, there was an increase of QTc interval, become 530 ms (Fig.1E) and CQ was discontinued. On follow-up ECG,\u00a0QTc interval returned to normal with normal sinus rhythm. He was discharged on the day 11th<\/sup>of his admission when the second RT-PCR was negative of SARS-CoV-2.<\/p>\n\n\n\n
\"Vol14No1_Chl_Put_fig1\"<\/a><\/td>\nFigure 1: Serial chest <\/strong>electrocardiography<\/strong> before chloroquinetreatment (A), prolonged QT interval during chloroquine treatment (B) and after chloroquine discontinuation (C) of the first and second COVID-19 patient.<\/strong><\/p>\n

Click here to view figure\u00a0<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Discussion<\/strong><\/p>\n

Apart to treat malaria, CQis frequently used in the management of rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders\u00a017-19<\/sup>.Recently,\u00a0without strong evidence of efficacy, CQ has been proposed as an effective treatment option of COVID-19.Cardiac toxicities induced CQis LQT, QRS widening, Torsade de\u00a0Pointes, cardiomyopathy, or ventricular arrhythmia. LQTis the most common cardiac adverse event of CQ treatment and this is the result of abnormal repolarization of the\u00a0ventricular myocardium resulting\u00a016<\/sup>. The mechanism by which HCQ or CQ causes LQT is not well understood. A study of sinoatrial node myocyte in guinea pig demonstrated\u00a0inhibitory effects of HCQ on the hyperpolarization activated current ion channels along with delayed rectifier potassium currents (\ud835\udc3cKr), and L-type calcium ion currents\u00a0(\ud835\udc3cCaL)20<\/sup>.This may associate with a proposed mechanism by which intractable action potentials in cardiac myocytes induced prolongation of QT interval due to inhibition of depolarization and repolarization from abnormal ion currents.<\/p>\n

In our presented cases, QT prolongation was more than 500 ms, denoting the high-risk group for malignant arrhythmia. There were no risk factors likely to serve as a risk factor\u00a0to have cardiotoxicity due to CQ use in both patients such as liver disease and renal impairment\u00a021<\/sup>. Discontinuation of CQ leaded to a dramatic delayed of LQT suggested the\u00a0LQT due to CQ itself.With CQ\/HCQ as one of the COVID-19 treatment candidates, the clinician needs to monitor the QT interval frequently\u00a022<\/sup>. Further investigation into the\u00a0mechanism of action of HCQ, and possible risk factors to have cardiac toxicities needs to be further elucidated.<\/p>\n

Conclusion <\/strong><\/p>\n

During awaiting adequate randomized controlled clinical trials, many national guidelines recommended CQ\/HCQ use as a therapeutic option of COVID-19. Although CQ\/HCQ\u00a0exhibit antiviral against SARS-CoV-2 and anti-inflammation properties on COVID-19 patients, its potential side effects especially cardiotoxicity should be considered to monitor during the therapy.<\/p>\n

Acknowledgment<\/strong><\/p>\n

We would like to thank to the patients and HT Editorial Service for the assistance during manuscript preparation.<\/p>\n

Conflict of Interest<\/strong><\/p>\n

Authors do not have any conflict of interests.<\/p>\n

Funding Source<\/strong><\/p>\n

This study received no external funding.<\/p>\n

References<\/strong><\/p>\n

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    Introduction Corona virus disease 2019 (COVID-19) pandemic, cause by severe […]<\/p>\n","protected":false},"author":14,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[88],"tags":[],"class_list":["post-37978","post","type-post","status-publish","format-standard","hentry","category-vol14no1"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/37978","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/14"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=37978"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/37978\/revisions"}],"predecessor-version":[{"id":40060,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/37978\/revisions\/40060"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=37978"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=37978"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=37978"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}