Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
BMJ Open ; 12(3): e048502, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1723715

ABSTRACT

BACKGROUND: To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. METHODS: We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach. RESULTS: We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo. DISCUSSION: Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.


Subject(s)
Adenosine Monophosphate/adverse effects , Alanine/adverse effects , COVID-19 , Hydroxychloroquine , Lopinavir/adverse effects , Ritonavir/adverse effects , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Drug Combinations , Humans , Hydroxychloroquine/adverse effects , Randomized Controlled Trials as Topic , SARS-CoV-2
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-324313

ABSTRACT

HBV infection is a major global health burden that needs novel immunotherapeutic approaches. Herein, we show that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a novel drug target for HBV infection. We reveal the new target with highly selective probes of PAC5, a natural sesquiterpene derivative. PAC5 show potent anti-HBV activity in vivo and in vitro. Further studies on its mode of action indicate that PAC5 binds to the residue Asp49 and a deep groove in the RNA recognition motif1 (RRM1) region of hnRNPA2B1. PAC5-bound hnRNPA2B1 is activated, dimerized, and translocated to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to the production of type I interferons (IFNs). Furthermore, PAC5 also suppresses other viral replications, such as SARS-CoV-2 and vesicular stomatitis virus (VSV). Our results indicate that PAC5 is the first small molecule agonist of hnRNPA2B1, a drug target potentially valid for broad-spectrum viral infections, providing a novel strategy for viral immunotherapy.

3.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5117-5122, 2021 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1485611

ABSTRACT

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.


Subject(s)
COVID-19/therapy , China , Evidence-Based Medicine , Humans , Medicine, Chinese Traditional , Practice Guidelines as Topic , SARS-CoV-2
4.
J Clin Epidemiol ; 139: 68-79, 2021 11.
Article in English | MEDLINE | ID: covidwho-1466592

ABSTRACT

OBJECTIVE: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. STUDY DESIGN: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. RESULTS: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. CONCLUSIONS: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. REGISTRATION: CRD42020192095.


Subject(s)
COVID-19/prevention & control , Randomized Controlled Trials as Topic/methods , Research Design/standards , COVID-19/epidemiology , Epidemiologic Studies , Humans
5.
J Evid Based Med ; 14(4): 313-332, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1462829

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , China , Humans , Medicine, Chinese Traditional , Pandemics , Practice Guidelines as Topic , SARS-CoV-2
6.
BMJ ; 374: n2231, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438073

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021). STUDY SELECTION: Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate. METHODS: After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm. RESULTS: As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative. CONCLUSION: In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a data supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321). READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).


Subject(s)
Antibodies, Viral/therapeutic use , COVID-19/therapy , Cell- and Tissue-Based Therapy/methods , SARS-CoV-2/immunology , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , Bayes Theorem , COVID-19/immunology , Clinical Trials as Topic , Humans , Immunization, Passive , Network Meta-Analysis , Treatment Outcome
7.
Front Pharmacol ; 12: 688857, 2021.
Article in English | MEDLINE | ID: covidwho-1378197

ABSTRACT

Background: Qingfei Paidu decoction (QFPD) has been widely used in treating COVID-19 in China. However, there is still a lack of comprehensive and systematic evidence to demonstrate the effectiveness and safety of QFPD. This study aims to evaluate the efficacy and safety of QFPD in patients with COVID-19. Methods: We searched seven databases up to 5 March 2021. Two reviewers independently screened studies, extracted data of interest, and assessed risk of bias. The Cochrane risk of bias tool was used to assess the risk of bias of randomized controlled trials. The Newcastle-Ottawa scale was used to assess the risk of bias of cohort and non-randomized trials. The "Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group" was adopted for controlled pre-post studies. We used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of evidence. We carried out a random effect meta-analysis using RevMan 5.3. For outcomes that could not be meta-analyzed, we performed a descriptive analysis. Results: We identified 16 studies with 11,237 patients, including one RCT, six non-randomized trials, two cohort studies, and seven pre-post studies. The certainty of evidence was low to very low because of the observational study design. QFPD combined with conventional treatment might decrease the time for nucleic acid conversion (MD = -4.78 days, 95% CI: -5.79 to -3.77), shorten the length of hospital stay (MD = -7.95 days, 95% CI: -14.66 to -1.24), shorten the duration of symptoms recovery of fever (MD = -1.51 days, 95% CI: -1.92 to -1.09), cough (MD = -1.64 days, 95% CI: -1.91 to -1.36) and chest CT (MD = -2.23 days, 95% CI: -2.46 to -2.00), improve the overall traditional Chinese medicine symptom scores (MD = 41.58 scores, 95% CI: 32.67 to 50.49), and change the laboratory indexes, such as WBC, AST, and CRP. Conclusion: QFPD combined with conventional treatment might be effective for patients with COVID-19. No serious adverse reactions related to QFPD were observed. Further high-quality studies are still needed in the future.

8.
BMJ ; 373: n949, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1203960

ABSTRACT

OBJECTIVE: To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. STUDY SELECTION: Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: The first iteration of this living network meta-analysis includes nine randomised trials-six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. CONCLUSIONS: Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Subject(s)
COVID-19 , Carrageenan/pharmacology , Global Health/statistics & numerical data , Hydroxychloroquine/pharmacology , Ivermectin/pharmacology , Anti-Infective Agents/pharmacology , COVID-19/prevention & control , Chemoprevention/methods , Chemoprevention/statistics & numerical data , Humans , SARS-CoV-2 , Treatment Outcome , Uncertainty
9.
Ann Palliat Med ; 10(2): 1488-1493, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1000754

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to grow worldwide, and systematic reviews (SRs)/meta-analyses (MAs) on COVID-19 can efficiently guide evidence-based clinical practice. However, SRs/MAs with weaknesses can mislead clinical practice and pose harm to patients, and too many useless SRs/MAs could pose confusion and waste sources. A "living" overview of SRs/MAs aims to provide an open, accessible and frequently updated resource summarizing the highest-level evidence of COVID-19, that can help evidence-users to quickly identify trusted evidence to guide the practice. This study aims to systematically give an overview SRs/MAs of COVID-19, assess their quality, and identify the best synthesis of evidence. METHODS: Databases including Medline, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM) and WanFang were systematically searched on May 1, 2020 using relevant terms for identify SRs/MAs related to COVID-19. The study selection, data extraction and quality assessment will be performed by independent reviewers, and results will be crosschecked. The authoritative tools (AMSTAR-2, PRISMA and its extensions) will be used to assess the methodological quality and reporting quality of included SRs/MAs, and potential influence factors will be explored. The consistency of conclusions will be compared among reviews and the best evidence will be summarized. In addition, we will conduct exploratory meta-analyses (MAs) of individual studies when applicable. Data will be reported as number with (or) percentage, risk ratio (RR) or odds ratio (OR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) according to the specific results. R3.6.1 and Microsoft Excel 2016 will be used to analyze and manage data. RESULTS: The results of this overview will be submitted to a peer-reviewed journal for publication. DISCUSSION: In this study, we will present for the first time, an overview of SRs/MAs, which provides a comprehensive, dynamic evidence landscape on prevalence, prevention, diagnosis, treatment, and prognosis of COVID-19.


Subject(s)
COVID-19 , Research Design , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/therapy , Databases, Bibliographic , Humans , Meta-Analysis as Topic , Systematic Reviews as Topic
10.
Kidney Int Rep ; 6(1): 24-45, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-898810

ABSTRACT

INTRODUCTION: Kidney transplant recipients are at increased susceptibility to many viral infections leading to justifiable anxiety about the effects of coronavirus disease 2019 (COVID-19). METHODS: We performed literature searches from multiple resources in April and August 2020 for relevant English and Chinese literature. Abstracts were screened, followed by full-text review with data extraction of reports that included at least 20 kidney transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and completed outcomes. RESULTS: Twenty studies had sufficient data, which we have summarized. Studies were predominantly descriptive and came from France, Italy, Spain, Turkey, United Kingdom, and United States. Quality assessment demonstrated limitations in selection of comparison groups and controlling for additional factors. Mortality rates from published studies were variable. Based on early data early from Spain, 46% of patients who developed COVID-19 within 60 days of transplantation died. Acute kidney injury was common, and mycophenolate was discontinued in most patients. CONCLUSION: Given the rapid global spread of COVID-19, reliable evidence is needed to inform public health policies. Hospitalized kidney transplant recipients with COVID-19 are at a high risk of death in early reports but interpretation of these data requires caution, as studies were susceptible to period effects. Reassuringly, the quality of observational data is improving. Detailed and comprehensive data collection through linked registries will be necessary to conduct accurate analyses of risk factors for adverse outcomes, not least given the risks of stopping imunosuppression. This report highlights the early mortality excess in transplant recipients but medium- and longer-term outcomes remain uncertain and merit careful investigation.

11.
BMJ ; 370: m2980, 2020 07 30.
Article in English | MEDLINE | ID: covidwho-691120

ABSTRACT

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. CONCLUSION: Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is publicly available in the supplementary material. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiration, Artificial/statistics & numerical data , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Betacoronavirus/pathogenicity , COVID-19 , Centers for Disease Control and Prevention, U.S./statistics & numerical data , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/virology , Databases, Factual/statistics & numerical data , Drug Combinations , Evidence-Based Medicine/methods , Evidence-Based Medicine/statistics & numerical data , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Network Meta-Analysis , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Standard of Care , Treatment Outcome , United States/epidemiology
12.
BMJ ; 370: m2924, 2020 07 30.
Article in English | MEDLINE | ID: covidwho-691027

ABSTRACT

CLINICAL QUESTION: What is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020. CURRENT PRACTICE: Remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice. RECOMMENDATIONS: The guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir. HOW THIS GUIDELINE WAS CREATED: An international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems. THE EVIDENCE: The linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay. UNDERSTANDING THE RECOMMENDATION: Most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/virology , Guideline Adherence , Humans , Length of Stay/statistics & numerical data , Network Meta-Analysis , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Severity of Illness Index , Time Factors , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL