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Article ; Online: Efficacy of Corticosteroids in COVID-19 Patients: A Systematic Review and Meta-Analysis

Tlayjeh, Haytham / Mhish, Olaa / Enani, Mushira / Alruwaili, Alya / Tleyjeh, Rana / Thalib, Lukman / Hassett, Leslie / Arabi, Yaseen / Kashour, Tarek / Tleyjeh, Imad

medRxiv

Abstract: Background: To systematically review the literature about the effect of systemic corticosteroid therapy (CST) on outcomes of COVID-19 patients. Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. ... ...

Abstract	Background: To systematically review the literature about the effect of systemic corticosteroid therapy (CST) on outcomes of COVID-19 patients. Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach. Results: Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I2=81.94 %). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I2=78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I2=43.38%). Conclusion: Heterogeneous and low certainty cumulative evidence suggests that CST lacks efficacy in reducing short-term mortality while possibly delaying viral clearance in patients hospitalized with COVID-19. Because of the discordant results between the single RCT and observational studies, more research should continue to identify the clinical and biochemical characteristics of patients population that could benefit from CST.
Keywords	covid19
Language	English
Publishing date	2020-08-14
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.08.13.20174201
Database	COVID19

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Article ; Online: Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis.

Tlayjeh, Haytham / Mhish, Olaa H / Enani, Mushira A / Alruwaili, Alya / Tleyjeh, Rana / Thalib, Lukman / Hassett, Leslie / Arabi, Yaseen M / Kashour, Tarek / Tleyjeh, Imad M

Journal of infection and public health

2020 Volume 13, Issue 11, Page(s) 1652–1663

Abstract: Background: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients.: Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to ...

Abstract	Background: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients. Methods: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach. Results: Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I Conclusion: In this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients' population that could benefit from CST.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy ; Hospitalization ; Humans ; Observational Studies as Topic ; Pandemics ; Pneumonia, Viral/drug therapy ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome
Chemical Substances	Adrenal Cortex Hormones
Keywords	covid19
Language	English
Publishing date	2020-09-29
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2467587-8
ISSN	1876-035X ; 1876-0341
ISSN (online)	1876-035X
ISSN	1876-0341
DOI	10.1016/j.jiph.2020.09.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis.

Tleyjeh, Imad M / Kashour, Zakariya / Damlaj, Moussab / Riaz, Muhammad / Tlayjeh, Haytham / Altannir, Mustafa / Altannir, Youssef / Al-Tannir, Mohamad / Tleyjeh, Rana / Hassett, Leslie / Kashour, Tarek

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2020 Volume 27, Issue 2, Page(s) 215–227

Abstract: Objectives: Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature ... ...

Abstract	Objectives: Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients. Methods: Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I Results: Of 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80-1.49, I Conclusions: Cumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; COVID-19/mortality ; COVID-19/therapy ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/mortality ; Cytokine Release Syndrome/therapy ; Humans ; Observational Studies as Topic ; Odds Ratio ; Randomized Controlled Trials as Topic ; Receptors, Interleukin-6/antagonists & inhibitors ; Respiration, Artificial/statistics & numerical data ; SARS-CoV-2 ; Safety ; COVID-19 Drug Treatment
Chemical Substances	Antibodies, Monoclonal, Humanized ; Receptors, Interleukin-6 ; tocilizumab (I031V2H011)
Keywords	covid19
Language	English
Publishing date	2020-11-05
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2020.10.036
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cardiac Toxicity of Chloroquine or Hydroxychloroquine in Patients With COVID-19: A Systematic Review and Meta-regression Analysis.

Tleyjeh, Imad M / Kashour, Zakariya / AlDosary, Oweida / Riaz, Muhammad / Tlayjeh, Haytham / Garbati, Musa A / Tleyjeh, Rana / Al-Mallah, Mouaz H / Sohail, M Rizwan / Gerberi, Dana / Bin Abdulhak, Aref A / Giudicessi, John R / Ackerman, Michael J / Kashour, Tarek

Mayo Clinic proceedings. Innovations, quality & outcomes

2020 Volume 5, Issue 1, Page(s) 137–150

Abstract: Objective: To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19).: Methods: We searched multiple data sources including ... ...

Abstract	Objective: To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19). Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences. Results: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; Conclusion: Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored.
Keywords	covid19
Language	English
Publishing date	2020-11-02
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4548
ISSN (online)	2542-4548
DOI	10.1016/j.mayocpiqo.2020.10.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis

Tlayjeh, Haytham / Mhish, Olaa H / Enani, Mushira A / Alruwaili, Alya / Tleyjeh, Rana / Thalib, Lukman / Hassett, Leslie / Arabi, Yaseen M / Kashour, Tarek / Tleyjeh, Imad M

J Infect Public Health

Abstract: BACKGROUND: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients. METHODS: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July ...

Abstract	BACKGROUND: To systematically review the literature about the association between systemic corticosteroid therapy (CST) and outcomes of COVID-19 patients. METHODS: We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach. RESULTS: Out of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I2 = 81.94%). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I2 = 78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I2 = 43.38%). CONCLUSION: In this systematic review, as of July 2020, heterogeneous and low certainty cumulative evidence based on observational studies and one RCT suggests that CST was not associated with reduction in short-term mortality but possibly with a delay in viral clearance in patients hospitalized with COVID-19 of different severities. However, the discordant results between the single RCT and observational studies as well as the heterogeneity observed across observational studies, call for caution in using observational data and suggests the need for more RCTs to identify the clinical and biochemical characteristics of patients' population that could benefit from CST.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #803118
Database	COVID19

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Article ; Online: Efficacy and safety of tocilizumab in COVID-19 patients

Tleyjeh, Imad M. / Kashour, Zakariya / Damlaj, Moussab / Riaz, Muhammad / Tlayjeh, Haytham / Altannir, Mustafa / Altannir, Youssef / Al-Tannir, Mohamad / Tleyjeh, Rana / Hassett, Leslie / Kashour, Tarek

Clinical Microbiology and Infection ; ISSN 1198-743X

A living systematic review and meta-analysis

2020

Keywords	Microbiology (medical) ; Infectious Diseases ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.1016/j.cmi.2020.10.036
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Association of corticosteroids use and outcomes in COVID-19 patients

Tlayjeh, Haytham / Mhish, Olaa H. / Enani, Mushira A. / Alruwaili, Alya / Tleyjeh, Rana / Thalib, Lukman / Hassett, Leslie / Arabi, Yaseen M. / Kashour, Tarek / Tleyjeh, Imad M.

Journal of Infection and Public Health

A systematic review and meta-analysis

2020 Volume 13, Issue 11, Page(s) 1652–1663

Keywords	Public Health, Environmental and Occupational Health ; Infectious Diseases ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ISSN	1876-0341
DOI	10.1016/j.jiph.2020.09.008
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

Tleyjeh, Imad / Kashour, Zakariya / AlDosary, Oweida / Riaz, Muhammad / Tlayjeh, Haytham / Garbati, Musa A / Tleyjeh, Rana / Al-Mallah, Mouaz H / Sohail, Rizwan M / Gerberi, Dana / Bin Abdulhak, Aref A / Giudicessi, John R / Ackerman, Michael John / Kashour, Tarek

medRxiv

Abstract: Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ... ...

Abstract	Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias. Data Extraction and Synthesis Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures Pooled Incidence of: (1) change in QTc value from baseline ≥ 60 ms, (2) QTc ≥ 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias. Results A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of ≥ 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc ≥ 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of ≥ 60 ms or QTc ≥ 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.
Keywords	covid19
Language	English
Publishing date	2020-06-18
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.06.16.20132878
Database	COVID19

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Article: The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

Abstract: Objective: To systematically review the literature and estimate the risk of Chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in COVID-19 patients. Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM ... ...

Abstract	Objective: To systematically review the literature and estimate the risk of Chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in COVID-19 patients. Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science, and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled COVID-19 patients treated with CQ or HCQ, with or without azithromycin and reported on cardiac toxicities. We performed a meta-analysis using the arcsine transformation of the different incidences. Results: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of ≥ 60 ms or QTc ≥ 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions: Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation and relatively higher incidence of TdP/VT/cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. COVID-19 patients who are treated with antimalarials for other indications should be adequately monitored.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #899296
Database	COVID19

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Article ; Online: The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis

Tleyjeh, Imad / Kashour, Zakariya / AlDosary, Oweida / Riaz, Muhammad / Tlayjeh, Haytham / Garbati, Musa A / Tleyjeh, Rana / Al-Mallah, Mouaz H / Sohail, Rizwan M / Gerberi, Dana / Abdulhak, Aref A Bin / Giudicessi, John R / Ackerman, Michael John / Kashour, Tarek

Abstract	Abstract Importance The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. Objective To systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data Sources A systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study Selection Studies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias. Data Extraction and Synthesis Study characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and Measures Pooled Incidence of: (1) change in QTc value from baseline [â¥] 60 ms, (2) QTc [â¥] 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias. Results A total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of [â¥] 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc [â¥] 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of [â¥] 60 ms or QTc [â¥] 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and Relevance Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
Note	WHO #Covidence: #20132878
DOI	10.1101/2020.06.16.20132878
Database	COVID19

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