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Article ; Online: Efficacy and safety of remdesivir in hospitalized Covid-19 patients: Systematic review and meta-analysis including network meta-analysis.

Elsawah, Hozaifa Khalil / Elsokary, Mohamed Ahmed / Abdallah, Mahmoud Samy / ElShafie, Ahmed Hanei

2020 Volume 31, Issue 4, Page(s) e2187

Abstract: ... of the pandemic, there is evidence that remdesivir can be safely administered for hospitalized Covid-19 patients ... it was increased by 14% among moderate and severe Covid-19 patients (RR = 1.14, 95%CI = 1.06-1.22 ... patients showed better response to remdesivir in the recovery (RR = 0.3, 95%CI = 0.13-0.7) and mortality ...

Abstract	Remdesivir is an antiviral agent that has shown broad-spectrum activity, including against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials investigating the role of remdesivir in coronavirus disease 2019 (Covid-19) reported conflicting results. This study aimed to systematically review the best available evidence and synthesize the results. Several electronic databases were searched for candidate studies up to 12 October 2020. Studies eligible for meta-analysis were selected based on the inclusion criteria. Primary outcomes are the recovery and mortality rates, while secondary outcomes are the safety profile of remdesivir. The main effective measures are the rate ratio (RR) and rate difference (RD). Four clinical trials and one observational study were included. Remdesivir treatment for 10 days increased the recovery rate on day 14 by 50% among severe Covid-19 patients (RR = 1.5, 95%CI = 1.33-1.7), while on day 28 it was increased by 14% among moderate and severe Covid-19 patients (RR = 1.14, 95%CI = 1.06-1.22). Additionally, remdesivir decreased the mortality rate on day 14 by 36% among all patients (RR = 0.64, 95%CI = 0.45-0.92) but not on day 28 (RR = 1.05, 95%CI = 0.56-1.97). Nonmechanically ventilated Covid-19 patients showed better response to remdesivir in the recovery (RR = 0.3, 95%CI = 0.13-0.7) and mortality (RR = 2.33, 95%CI = 1.24-4.4) rates on day 14. Remdesivir reduced serious adverse effects by absolute 6% and no significant Grade 3 or 4 adverse effects were reported. At this early stage of the pandemic, there is evidence that remdesivir can be safely administered for hospitalized Covid-19 patients. It improves the recovery rate in both moderate and severe patients but, the optimal effect is achieved for those who are severely affected but not mechanically ventilated.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Humans ; Network Meta-Analysis ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
Keywords	covid19
Language	English
Publishing date	2020-10-31
Publishing country	England
Document type	Journal Article ; Review ; Comment
ZDB-ID	1086043-5
ISSN	1099-1654 ; 1052-9276
ISSN (online)	1099-1654
ISSN	1052-9276
DOI	10.1002/rmv.2187
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Article: Efficacy and safety of remdesivir in hospitalized Covid-19 patients: Systematic review and meta-analysis including network meta-analysis

Elsawah, Hozaifa Khalil / Elsokary, Mohamed Ahmed / Abdallah, Mahmoud Samy / ElShafie, Ahmed Hanei

Rev Med Virol

Abstract	Remdesivir is an antiviral agent that has shown broad-spectrum activity, including against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical trials investigating the role of remdesivir in coronavirus disease 2019 (Covid-19) reported conflicting results. This study aimed to systematically review the best available evidence and synthesize the results. Several electronic databases were searched for candidate studies up to 12 October 2020. Studies eligible for meta-analysis were selected based on the inclusion criteria. Primary outcomes are the recovery and mortality rates, while secondary outcomes are the safety profile of remdesivir. The main effective measures are the rate ratio (RR) and rate difference (RD). Four clinical trials and one observational study were included. Remdesivir treatment for 10 days increased the recovery rate on day 14 by 50% among severe Covid-19 patients (RR = 1.5, 95%CI = 1.33-1.7), while on day 28 it was increased by 14% among moderate and severe Covid-19 patients (RR = 1.14, 95%CI = 1.06-1.22). Additionally, remdesivir decreased the mortality rate on day 14 by 36% among all patients (RR = 0.64, 95%CI = 0.45-0.92) but not on day 28 (RR = 1.05, 95%CI = 0.56-1.97). Nonmechanically ventilated Covid-19 patients showed better response to remdesivir in the recovery (RR = 0.3, 95%CI = 0.13-0.7) and mortality (RR = 2.33, 95%CI = 1.24-4.4) rates on day 14. Remdesivir reduced serious adverse effects by absolute 6% and no significant Grade 3 or 4 adverse effects were reported. At this early stage of the pandemic, there is evidence that remdesivir can be safely administered for hospitalized Covid-19 patients. It improves the recovery rate in both moderate and severe patients but, the optimal effect is achieved for those who are severely affected but not mechanically ventilated.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #893252
Database	COVID19

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Article ; Online: Clinical efficacy and safety of remdesivir in patients with COVID-19: a systematic review and network meta-analysis of randomized controlled trials.

Lai, Chih-Cheng / Chen, Chao-Hsien / Wang, Cheng-Yi / Chen, Kuang-Hung / Wang, Ya-Hui / Hsueh, Po-Ren

The Journal of antimicrobial chemotherapy

2021 Volume 76, Issue 8, Page(s) 1962–1968

Abstract: ... Conclusions: Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 ... Objectives: We performed a systematic review and network meta-analysis ... in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens ...

Abstract	Objectives: We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in treating coronavirus disease 2019 (COVID-19). Methods: PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020. Results: Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group [OR = 1.68 (95% CI 1.18-2.40)], with no significant difference observed between the 10 day and placebo groups [OR = 1.23 (95% CI 0.90-1.68)]. Patients receiving remdesivir revealed a greater likelihood of discharge [10 day remdesivir versus control: OR = 1.32 (95% CI 1.09-1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28-2.35)] and recovery [10 day remdesivir versus control: OR = 1.29 (95% CI 1.03-1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31-2.48)] than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events. Conclusions: Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; COVID-19/drug therapy ; Humans ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; SARS-CoV-2 ; Treatment Outcome
Chemical Substances	remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2021-03-23
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkab093
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: An updated systematic review and network meta-analysis of 25 randomized trials assessing the efficacy and safety of treatments in COVID-19 disease.

Diallo, Alhassane / Carlos-Bolumbu, Miguel / Traoré, Marie / Diallo, Mamadou Hassimiou / Jedrecy, Christophe

Journal of public health research

2021 Volume 10, Issue 1, Page(s) 1945

Abstract: ... an update network meta-analysis to compare and rank COVID-19 treatments according to their efficacy and ... and 50% (0.50, 0.25-0.98) respectively. In this study of hospitalized patients with COVID-19 ... standard care or placebo 28-day after hospitalization in adult patients with COVID-19 disease were included ...

Abstract	To date, there is no definite effective treatment for the COVID- 19 pandemic. We performed an update network meta-analysis to compare and rank COVID-19 treatments according to their efficacy and safety. Literature search was performed from MEDLINE and CENTRAL databases from inception to September 5, 2020. Randomized clinical trials (RCTs) which compared the effect of any pharmacological drugs versus standard care or placebo 28-day after hospitalization in adult patients with COVID-19 disease were included. Risk ratio (RR) and 95% CI were calculated for 28-day all-cause mortality, clinical improvement, any adverse event (AEs), and viral clearance. A total of 25 RCTs, evaluating 17 different treatments, and 11,597 participants were analyzed. Remdesivir for 10- day compared to standard care (RR 0.69, 95% CI [0.48-0.99]), and a low dose compared to a high dose of HCQ (0.38, [0.17-0.89]) were associated with a lower risk of death. A total of 2,766 patients experienced clinical improvement, a 5-day course of remdesivir was associated with a higher frequency of clinical improvement compared to standard care (RR 1.21, 95% CI [1.00-1.47]). Compared to standard care, remdesivir for both 5 and 10 days, lopinavir/ritonavir, and dexamethasone reduced the risk of any severe AEs by 52% (0.48, 0.34-0.67), 24% (0.77, 0.63-0.92), 40% (0.60, 0.37-0.98), and 50% (0.50, 0.25-0.98) respectively. In this study of hospitalized patients with COVID-19, administration of remdesivir for 10-day compared to standard care was associated with lower 28-day all-cause mortality and serious AEs, and higher clinical improvement rate.
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article
ISSN	2279-9028
ISSN	2279-9028
DOI	10.4081/jphr.2021.1945
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Article ; Online: Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis.

Kim, Min Seo / An, Min Ho / Kim, Won Jun / Hwang, Tae-Ho

PLoS medicine

2020 Volume 17, Issue 12, Page(s) e1003501

Abstract: ... meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological ... of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require ... of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac ...

Abstract	Background: Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. Methods and findings: We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527). Conclusions: In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.
MeSH term(s)	Adenosine Monophosphate/adverse effects ; Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/therapeutic use ; Alanine/adverse effects ; Alanine/analogs & derivatives ; Alanine/therapeutic use ; Anti-Inflammatory Agents/adverse effects ; Anti-Inflammatory Agents/therapeutic use ; Azithromycin/adverse effects ; Azithromycin/therapeutic use ; COVID-19/mortality ; COVID-19/therapy ; Critical Illness ; Hospitalization ; Humans ; Hydroxychloroquine/adverse effects ; Hydroxychloroquine/therapeutic use ; Immunization, Passive ; Network Meta-Analysis ; Observational Studies as Topic ; Randomized Controlled Trials as Topic ; COVID-19 Drug Treatment ; COVID-19 Serotherapy
Chemical Substances	Anti-Inflammatory Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Hydroxychloroquine (4QWG6N8QKH) ; Azithromycin (83905-01-5) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2020-12-30
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1003501
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Article: The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Lai, Chih-Cheng / Wang, Ya-Hui / Chen, Kuang-Hung / Chen, Chao-Hsien / Wang, Cheng-Yi

Viruses. 2022 Aug. 02, v. 14, no. 8

2022

Abstract: This network meta-analysis compared the clinical efficacy and safety of anti-viral agents ... that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three ... for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web ...

Abstract	This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.
Keywords	COVID-19 infection ; death ; disease prevention ; disease progression ; intravenous injection ; meta-analysis ; placebos ; risk ; systematic review
Language	English
Dates of publication	2022-0802
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081706
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: An updated systematic review and network meta-analysis of 25 randomized trials assessing the efficacy and safety of treatments in COVID-19 disease

Alhassane Diallo / Miguel Carlos-Bolumbu / Marie Traoré / Mamadou Hassimiou Diallo / Christophe Jedrecy

Journal of Public Health Research, Vol 10, Iss

2021 Volume 1

Abstract: ... network meta-analysis to compare and rank COVID-19 treatments according to their efficacy and safety ... and 50% (0.50, 0.25–0.98) respectively. In this study of hospitalized patients with COVID-19 ... or placebo 28-day after hospitalization in adult patients with COVID-19 disease were included ...

Abstract	To date, there is no definite effective treatment for the COVID-19 pandemic. We performed an update network meta-analysis to compare and rank COVID-19 treatments according to their efficacy and safety. Literature search was performed from MEDLINE and CENTRAL databases from inception to September 5, 2020. Randomized clinical trials (RCTs) which compared the effect of any pharmacological drugs versus standard care or placebo 28-day after hospitalization in adult patients with COVID-19 disease were included. Risk ratio (RR) and 95% CI were calculated for 28-day all-cause mortality, clinical improvement, any adverse event (AEs), and viral clearance. A total of 25 RCTs, evaluating 17 different treatments, and 11,597 participants were analyzed. Remdesivir for 10-day compared to standard care (RR 0.69, 95% CI [0.48–0.99]), and a low dose compared to a high dose of HCQ (0.38, [0.17–0.89]) were associated with a lower risk of death. A total of 2,766 patients experienced clinical improvement, a 5-day course of remdesivir was associated with a higher frequency of clinical improvement compared to standard care (RR 1.21, 95% CI [1.00–1.47]). Compared to standard care, remdesivir for both 5 and 10 days, lopinavir/ritonavir, and dexamethasone reduced the risk of any severe AEs by 52% (0.48, 0.34–0.67), 24% (0.77, 0.63–0.92), 40% (0.60, 0.37–0.98), and 50% (0.50, 0.25–0.98) respectively. In this study of hospitalized patients with COVID-19, administration of remdesivir for 10-day compared to standard care was associated with lower 28-day all-cause mortality and serious AEs, and higher clinical improvement rate.
Keywords	SARS-CoV-2 ; COVID-19 ; network meta-analysis ; treatment ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	PAGEPress Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients

Kim, Min Seo / An, Min Ho / Kim, Won Jun / Hwang, Tae-Ho

medRxiv

Abstract: ... and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine ... review and network meta-analysis Data Sources: PubMed, Google Scholar, MEDLINE, the Cochrane Library ... Objective: To evaluate the comparative efficacy and safety of pharmacological interventions used ...

Abstract	Objective: To evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. Design: Systematic review and network meta-analysis Data Sources: PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study Selection: Published and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome Measures: The outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: 49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). Conclusion: Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review Registration: PROSPERO 2020: CRD42020186527.
Keywords	covid19
Language	English
Publishing date	2020-06-19
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.06.15.20132407
Database	COVID19

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Article ; Online: Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis of confounder-adjusted 20212 hospitalized patients

Kim, M. S. / An, M. H. / Kim, W. J. / Hwang, T.-H.

Abstract	Objective: To evaluate the comparative efficacy and safety of pharmacological interventions used in treating COVID-19 and form a basis for an evidence-based guideline of COVID-19 management by evaluating the level of evidence behind each treatment regimen in different clinical settings. Design: Systematic review and network meta-analysis Data Sources: PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov up to June 9th, 2020. Study Selection: Published and unpublished randomized controlled trials (RCTs) and baseline-adjusted observational studies which met our predefined eligibility criteria. Main Outcome Measures: The outcomes of interest were mortality, progression to severe disease (severe pneumonia or admission to intensive care unit (ICU)), time to viral clearance, QT prolongation, fatal cardiac complications, and non-cardiac serious adverse events. The level of evidence behind each outcome was also measured using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: 49 studies with a total of 20212 confounder-adjusted patients were included for analysis. The risk of progression to severe pneumonia or ICU admission was significantly reduced with tocilizumab (GRADE low), anakinra (GRADE very low), and remdesivir (GRADE high) compared to standard care. Tocilizumab was shown to reduce mortality rate for both moderate-severe patients in the non-ICU setting at admission (Odds ratio (OR) 0.31, 95% confidence interval (CI) 0.18 to 0.54, GRADE low) and critically ill patients in the ICU setting (OR 0.67, 95% CI 0.50 to 0.91, GRADE low). High dose IVIG reduced death rate (GRADE low) while corticosteroids increased mortality for critically ill patients (GRADE moderate). Convalescent plasma and hydroxychloroquine were shown to promote viral clearance (OR 11.39, 95% CI 3.91 to 33.18, GRADE low and OR 6.08, 95% CI 2.74 to 13.48, GRADE moderate, respectively) while not altering mortality or progression to the severe courses. The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 1,85, 95% CI 1.05 to 3.26, GRADE low) and fatal cardiac complications in cardiac-impaired populations (OR 2.26, 95% CI 1.26 to 4.05, GRADE low). High-dose (>600mg/day) hydroxychloroquine monotherapy was significantly associated with increased non-cardiac serious adverse events (GRADE moderate). Conclusion: Anti-inflammatory agents (tocilizumab, anakinra, and IVIG) and remdesivir may safely and effectively improve outcomes of hospitalized COVID-19 patients. Widely used hydroxychloroquine provides marginal clinical benefit in improving viral clearance rates whilst posing both cardiac and non-cardiac safety risks, especially in the vulnerable population. Only 20% of current evidence on pharmacological management of COVID-19 is on moderate and high evidence certainty; remaining 80% are of low or very low certainty and warrant further studies to establish firm conclusions. Systematic Review Registration: PROSPERO 2020: CRD42020186527.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.06.15.20132407
Database	COVID19

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