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1.
Chin Med J (Engl) ; 134(16): 1920-1929, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1522371

ABSTRACT

BACKGROUND: The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19. METHODS: Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size. RESULTS: Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20-0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75-0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60-2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05-1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38-0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20-5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02-7.08) vs. SOC with very low quality were associated with an increased risk. CONCLUSIONS: COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.


Subject(s)
COVID-19 , Humans , Medicine, Chinese Traditional , Network Meta-Analysis , Pandemics , SARS-CoV-2
2.
Front Public Health ; 9: 729559, 2021.
Article in English | MEDLINE | ID: covidwho-1470772

ABSTRACT

Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19). Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications. Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates. Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.


Subject(s)
COVID-19 , Bayes Theorem , COVID-19/therapy , Humans , Immunization, Passive , Network Meta-Analysis , Randomized Controlled Trials as Topic , SARS-CoV-2
3.
Am J Obstet Gynecol MFM ; 3(3): 100312, 2021 05.
Article in English | MEDLINE | ID: covidwho-1453982

ABSTRACT

OBJECTIVE: This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth. DATA SOURCES: The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted. STUDY ELIGIBILITY CRITERIA: Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study. METHODS: Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability. RESULTS: A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62-1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80-1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56-1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, -49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45-1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24-2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72-6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96-2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis. CONCLUSION: Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.


Subject(s)
Premature Birth , Bayes Theorem , Betamethasone , Child , Dexamethasone/therapeutic use , Female , Humans , Infant , Infant, Newborn , Network Meta-Analysis , Pregnancy , Premature Birth/epidemiology
4.
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
5.
Aging (Albany NY) ; 13(18): 21866-21902, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1417381

ABSTRACT

BACKGROUND: Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs). METHODS: We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates. RESULTS: From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients. CONCLUSION: We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/therapeutic use , COVID-19/mortality , Humans , Imatinib Mesylate/therapeutic use , Network Meta-Analysis , Oxazoles/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Sulfonamides/therapeutic use , Thiohydantoins/therapeutic use , Treatment Outcome
6.
Medicine (Baltimore) ; 100(34): e27026, 2021 Aug 27.
Article in English | MEDLINE | ID: covidwho-1375240

ABSTRACT

BACKGROUND: There is no definite conclusion about comparison of better effectiveness between N95 respirators and medical masks in preventing health-care workers (HCWs) from respiratory infectious diseases, so that conflicting results and recommendations regarding the protective effects may cause difficulties for selection and compliance of respiratory personal protective equipment use for HCWs, especially facing with pandemics of corona virus disease 2019. METHODS: We systematically searched MEDLINE, Embase, PubMed, China National Knowledge Infrastructure, Wanfang, medRxiv, and Google Scholar from initiation to November 10, 2020 for randomized controlled trials, case-control studies, cohort studies, and cross-sectional studies that reported protective effects of masks or respirators for HCWs against respiratory infectious diseases. We gathered data and pooled differences in protective effects according to different types of masks, pathogens, occupations, concurrent measures, and clinical settings. The study protocol is registered with PROSPERO (registration number: 42020173279). RESULTS: We identified 4165 articles, reviewed the full text of 66 articles selected by abstracts. Six randomized clinical trials and 26 observational studies were included finally. By 2 separate conventional meta-analyses of randomized clinical trials of common respiratory viruses and observational studies of pandemic H1N1, pooled effects show no significant difference between N95 respirators and medical masks against common respiratory viruses for laboratory-confirmed respiratory virus infection (risk ratio 0.99, 95% confidence interval [CI] 0.86-1.13, I2 = 0.0%), clinical respiratory illness (risk ratio 0.89, 95% CI 0.45-1.09, I2 = 83.7%, P = .002), influenza-like illness (risk ratio 0.75, 95% CI 0.54-1.05, I2 = 0.0%), and pandemic H1N1 for laboratory-confirmed respiratory virus infection (odds ratio 0.92, 95% CI 0.49-1.70, I2 = 0.0%, P = .967). But by network meta-analysis, N95 respirators has a significantly stronger protection for HCWs from betacoronaviruses of severe acute respiratory syndrome, middle east respiratory syndrome, and corona virus disease 2019 (odds ratio 0.43, 95% CI 0.20-0.94). CONCLUSIONS: Our results provide moderate and very-low quality evidence of no significant difference between N95 respirators and medical masks for common respiratory viruses and pandemic H1N1, respectively. And we found low quality evidence that N95 respirators had a stronger protective effectiveness for HCWs against betacoronaviruses causative diseases compared to medical masks. The evidence of comparison between N95 respirators and medical masks for corona virus disease 2019 is open to question and needs further study.


Subject(s)
Health Personnel , Masks , N95 Respirators , Respiratory Tract Infections/prevention & control , Virus Diseases/prevention & control , Betacoronavirus , Coronavirus Infections/prevention & control , Humans , Infection Control/methods , Influenza A Virus, H1N1 Subtype , Influenza, Human/prevention & control , Network Meta-Analysis , Respiratory Tract Infections/virology
7.
J Breath Res ; 15(4)2021 09 13.
Article in English | MEDLINE | ID: covidwho-1361738

ABSTRACT

During the ongoing COVID-19 pandemic, face masks are among the most common and practical control measures used globally in reducing the risk of infection and disease transmission. Although several studies have investigated the efficacy of various face masks and respirators in preventing infection, the results have been inconsistent. Therefore, we performed a systematic review and network meta-analysis (NMA) of the randomized-controlled trials (RCTs) to assess the actual efficacy of face masks in preventing respiratory infections. We searched nine electronic databases up to July 2020 to find potential articles. We accepted trials reporting the protective efficacy of face masks against respiratory infections, of which the primary endpoint was the presence of respiratory infections. We used the ROB-2 Cochrane tool to grade the trial quality. We initially registered the protocol for this study in PROSPERO (CRD42020178516). Sixteen RCTs involving 17 048 individuals were included for NMA. Overall, evidence was weak, lacking statistical power due to the small number of participants, and there was substantial inconsistency in our findings. In comparison to those without face masks, participants with fit-tested N95 respirators were likely to have lesser infection risk (RR 0.67, 95% CI 0.38-1.19,P-score 0.80), followed by those with non-fit-tested N95 and non-fit-tested FFP2 respirators that shared the similar risk, (RR 0.73, 95% CI 0.12-4.36,P-score 0.63) and (RR 0.80, 95% CI 0.38-1.71,P-score 0.63), respectively. Next, participants who donned face masks with and without hand hygiene practices showed modest risk improvement alike (RR 0.89, 95% CI 0.67-1.17,P-score 0.55) and (RR 0.92, 95% CI 0.70-1.22,P-score 0.51). Otherwise, participants donning double-layered cloth masks were prone to infection (RR 4.80, 95% CI 1.42-16.27,P-score 0.01). Eleven out of 16 RCTs that underwent a pairwise meta-analysis revealed a substantially lower infection risk in those donning medical face masks (MFMs) than those without face masks (RR 0.83 95% CI 0.71-0.96). Given the body of evidence through a systematic review and meta-analyses, our findings supported the protective benefits of MFMs in reducing respiratory transmissions, and the universal mask-wearing should be applied-especially during the COVID-19 pandemic. More clinical data is required to conclude the efficiency of cloth masks; in the short term, users should not use cloth face masks in the outbreak hot spots and places where social distancing is impossible.


Subject(s)
COVID-19/prevention & control , Communicable Disease Control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Masks , Respiratory Protective Devices , Respiratory Tract Infections/prevention & control , Breath Tests , Humans , Network Meta-Analysis , Occupational Exposure , Randomized Controlled Trials as Topic , Respiratory Tract Infections/transmission , SARS-CoV-2
8.
JAMA Netw Open ; 4(8): e2119151, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1355856

ABSTRACT

Importance: Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events. Objective: To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children. Data Sources: Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020). Study Selection: Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo. Data Extraction and Synthesis: Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020. Main Outcomes and Measures: The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting). Results: A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41). Conclusions and Relevance: In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.


Subject(s)
Antiviral Agents/therapeutic use , Dibenzothiepins/therapeutic use , Enzyme Inhibitors/therapeutic use , Influenza, Human/drug therapy , Morpholines/therapeutic use , Pyridones/therapeutic use , Triazines/therapeutic use , Zanamivir/therapeutic use , Adolescent , Adult , Child , Endonucleases/antagonists & inhibitors , Female , Humans , Influenza A virus/drug effects , Influenza, Human/virology , Male , Middle Aged , Network Meta-Analysis , Neuraminidase/antagonists & inhibitors , Randomized Controlled Trials as Topic , Seasons , Young Adult
9.
J Med Virol ; 93(12): 6737-6749, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1347414

ABSTRACT

Chloroquine or its derivative hydroxychloroquine (HCQ) combined with or without azithromycin (AZ) have been widely investigated in observational studies as a treatment option for coronavirus 2019 (COVID-19) infection. The network meta-analysis aims to summarize evidence from randomized controlled trials (RCTs) to determine if AZ or HCQ is associated with improved clinical outcomes. PubMed and Embase were searched from inception to March 7, 2021. We included published RCTs that investigated the efficacy of AZ, HCQ, or its combination among hospitalized patients with COVID-19 infection. The outcomes of interest were all-cause mortality and the use of mechanical ventilation. The pooled odds ratio was calculated using a random-effect model. A total of 10 RCTs were analyzed. Participant's mean age ranged from 40.4 to 66.5 years. There was no significant effect on mortality associated with AZ plus HCQ (odds ratio [OR] = 0.562 [95% confidence interval {CI}: 0.168-1.887]), AZ alone (OR = 0.965 [95% CI: 0.865-1.077]), or HCQ alone (OR = 1.122 [95% CI: 0.995-1.266]; p = 0.06). Similarly, based on pooled effect sizes derived from direct and indirect evidence, none of the treatments had a significant benefit in decreasing the use of mechanical ventilation. No heterogeneity was identified (Cochran's Q = 1.68; p = 0.95; τ2 = 0; I2 = 0% [95% CI: 0%-0%]). Evidence from RCTs suggests that AZ with or without HCQ was not associated with a significant effect on the mortality or mechanical ventilation rates in hospitalized patients with COVID-19. More research is needed to explore therapeutics agents that can effectively reduce the mortality or severity of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Adult , Aged , Chloroquine/therapeutic use , Female , Humans , Male , Middle Aged , Network Meta-Analysis , Randomized Controlled Trials as Topic , Respiration, Artificial/methods
10.
J Occup Health ; 63(1): e12243, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1300344

ABSTRACT

OBJECTIVES: Work related stress is a major occupational health problem that is associated with adverse effects on physical and mental health. Healthcare workers are particularly vulnerable in the era of COVID-19. Physical methods of stress relief such as yoga and massage therapy may reduce occupational stress. The objective of this systematic review and network meta-analysis is to determine the effects of yoga, massage therapy, progressive muscle relaxation, and stretching on alleviating stress and improving physical and mental health in healthcare workers. METHODS: Databases were searched for randomized controlled trials on the use of physical relaxation methods for occupational stress in healthcare workers with any duration of follow-up. Meta-analysis was performed for standard mean differences in stress measures from baseline between subjects undergoing relaxation vs non-intervention controls. Network meta-analysis was conducted to determine the best relaxation method. RESULTS: Fifteen trials representing 688 healthcare workers were identified. Random-effects meta-analysis shows that physical relaxation methods overall reduced measures of occupational stress at the longest duration of follow-up vs baseline compared to non-intervention controls (SMD -0.53; 95% CI [-0.74 to -0.33]; p < .00001). On network meta-analysis, only yoga alone (SMD -0.71; 95% CI [-1.01 to -0.41]) and massage therapy alone (SMD -0.43; 95% CI [-0.72 to -0.14]) were more effective than control, with yoga identified as the best method (p-score = .89). CONCLUSION: Physical relaxation may help reduce occupational stress in healthcare workers. Yoga is particularly effective and offers the convenience of online delivery. Employers should consider implementing these methods into workplace wellness programs.


Subject(s)
COVID-19/psychology , Occupational Stress/psychology , Relaxation Therapy/psychology , Workplace/psychology , Yoga/psychology , Health Personnel/psychology , Humans , Network Meta-Analysis , Occupational Health , Randomized Controlled Trials as Topic
11.
Genes (Basel) ; 12(7)2021 06 25.
Article in English | MEDLINE | ID: covidwho-1295802

ABSTRACT

Peripheral blood transcriptome is a highly promising area for biomarker development. However, transcript abundances (TA) in these cell mixture samples are confounded by proportions of the component leukocyte subpopulations. This poses a challenge to clinical applications, as the cell of origin of any change in TA is not known without prior cell separation procedure. We developed a framework to develop a cell-type informative TA biomarkers which enable determination of TA of a single cell-type (B lymphocytes) directly in cell mixture samples of peripheral blood (e.g., peripheral blood mononuclear cells, PBMC) without the need for subpopulation separation. It is applicable to a panel of genes called B cell informative genes. Then a ratio of two B cell informative genes (a target gene and a stably expressed reference gene) obtained in PBMC was used as a new biomarker to represent the target gene expression in purified B lymphocytes. This approach, which eliminates the tedious procedure of cell separation and directly determines TA of a leukocyte subpopulation in peripheral blood samples, is called the Direct LS-TA method. This method is applied to gene expression datasets collected in influenza vaccination trials as early predictive biomarkers of seroconversion. By using TNFRSF17 or TXNDC5 as the target genes and TNFRSF13C or FCRLA as the reference genes, the Direct LS-TA B cell biomarkers were determined directly in the PBMC transcriptome data and were highly correlated with TA of the corresponding target genes in purified B lymphocytes. Vaccination responders had almost a 2-fold higher Direct LS-TA biomarker level of TNFRSF17 (log 2 SMD = 0.84, 95% CI = 0.47-1.21) on day 7 after vaccination. The sensitivity of these Direct LS-TA biomarkers in the prediction of seroconversion was greater than 0.7 and area-under curves (AUC) were over 0.8 in many datasets. In this paper, we report a straightforward approach to directly estimate B lymphocyte gene expression in PBMC, which could be used in a routine clinical setting. Moreover, the method enables the practice of precision medicine in the prediction of vaccination response. More importantly, seroconversion could now be predicted as early as day 7. As the acquired immunology pathway is common to vaccination against influenza and COVID-19, these biomarkers could also be useful to predict seroconversion for the new COVID-19 vaccines.


Subject(s)
B-Lymphocytes/physiology , Gene Expression , Influenza Vaccines/immunology , Seroconversion/genetics , B-Cell Activation Factor Receptor/genetics , Biomarkers/analysis , COVID-19 Vaccines/immunology , Computational Biology/methods , Databases, Genetic , Humans , Leukocytes, Mononuclear/physiology , Models, Theoretical , Network Meta-Analysis , Protein Disulfide-Isomerases/genetics , ROC Curve , Receptors, Fc/genetics , Seroconversion/physiology
12.
Alcohol Clin Exp Res ; 45(4): 675-688, 2021 04.
Article in English | MEDLINE | ID: covidwho-1199629

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta-analysis was conducted to examine possible relationships between EtOH consumption and COVID-19 pathologies. METHODS: Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID-19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID-19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA-sequencing data of autopsied lungs of COVID-19 patients retrieved from the GEO database. Network meta-analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA). RESULTS: Twenty-eight studies reporting significant gene expression changes in COVID-19 patients were identified. One RNA-sequencing dataset on autopsied lungs of COVID-19 patients was retrieved from GEO. Our network meta-analysis suggests that EtOH exposure may augment the effects of SARS-CoV-2 infection on hepatic fibrosis signaling pathway, cellular metabolism and homeostasis, inflammation, and neuroinflammation. EtOH may also enhance the activity of key mediators including cytokines, such as IL-1ß, IL-6, and TNF, and transcription factors, such as JUN and STAT, while inhibiting the activity of anti-inflammatory mediators including glucocorticoid receptor. Furthermore, IL-1ß, IL-6, TNF, JUN, and STAT were mapped to 10 pathways predicted to associate with SARS-CoV-2 proteins, including HMGB1, IL-1, and IL-6 signaling pathways. CONCLUSIONS: Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.


Subject(s)
Alcohol Drinking/epidemiology , Alcohol Drinking/metabolism , COVID-19/epidemiology , COVID-19/metabolism , Ethanol/adverse effects , Alcohol Drinking/genetics , COVID-19/genetics , Cytokines/genetics , Cytokines/metabolism , Ethanol/administration & dosage , Gene Expression Profiling/methods , Gene Regulatory Networks/physiology , Humans , Inflammation Mediators/metabolism , Network Meta-Analysis
13.
J Med Virol ; 93(2): 1171-1174, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196457

ABSTRACT

Several randomized clinical trials (RCTs) that investigated the effectiveness of remdesivir for the treatment of coronavirus disease-2019 (COVID-19) have generated inconsistent evidence. The present study aimed to synthesize available RCT evidence using network meta-analyses (NMAs). Both blinded and open-label RCTs in PubMed database from inception to 7 June 2020 that contained "remdesivir", "Covid-19", and "trial" in the abstracts conducted on hospitalized COVID-19 persons were identified and screened. The studies must have at least one remdesivir arm and evaluated one of the pre-specified outcomes. The outcomes were clinical improvement between days 10 to 15 after randomization and clinical recovery during the follow-up period. The identified literature was supplemented with relatively recent studies that were known to the researchers if not already included. Frequentist NMAs with random effects were conducted. Both 10-day and 5-day remdesivir regimens were associated with higher odds of clinical improvement (odds ratio [OR] of 10-day regimen: 1.35, 95% confidence interval [CI], 1.09-1.67); OR of 5-day regimen: 1.81, 95% CI, 1.32-2.45, and higher probabilities of clinical recovery (relative risk [RR] of 10-day regimen: 1.24, 95% CI, 1.07-1.43; RR of 5-day regimen: 1.47, 95% CI, 1.16-1.87 compared with placebo. Remdesivir may have clinical benefits among hospitalized COVID-19 persons.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Network Meta-Analysis , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Hospitalization/statistics & numerical data , Humans , Treatment Outcome
14.
J Antimicrob Chemother ; 76(8): 1962-1968, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1147983

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.


Subject(s)
COVID-19 , 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
15.
Am J Health Syst Pharm ; 78(8): 697-704, 2021 03 31.
Article in English | MEDLINE | ID: covidwho-1087686

ABSTRACT

PURPOSE: This article assesses the relative efficacy and safety of infliximab biosimilars in treatment of patients with rheumatoid arthritis (RA). METHODS: A frequentist, random-effects network meta-analysis was performed to evaluate evidence from randomized controlled trials that examined the use of infliximab biosimilars for treatment of patients with RA. PubMed/MEDLINE and other sources were searched for reports evaluating rates of response to treatment with the reference product (infliximab) vs an infliximab biosimilar. The primary efficacy outcome of interest was the rate of attainment of ACR20 (ie, 20% improvement in American College of Rheumatology core measures). The primary safety outcome was the rate of treatment-related serious adverse events (SAEs). Data were extracted by the primary author, and an assessment for risks of methodological bias was performed for each evaluated study. RESULTS: Five studies that enrolled a total of 2,499 patients were included. Overall comparisons using odds ratios and 95% confidence intervals (CIs) did not indicate statistically significant differences in response to treatment with biosimilar agents relative to each other or the infliximab reference product. ORs for ACR20 response for biosimilars vs infliximab were as follows: 1.475 (95% CI, 0.940-2.315) for infliximab-axxq, 1.259 (95% CI, 0.854-1.855) for infliximab-dyyb, 0.865 (95% CI, 0.5511.358) for infliximab-qbtx, and 0.832 (95% CI, 0.506-1.367) for infliximab-abda. Similar findings were observed in reported SAE rates among patients treated with the various biosimilars. CONCLUSION: ACR20 response appears to be comparable and nonsignificantly different between infliximab biosimilars. In the absence of any meaningful differences in safety or efficacy, biosimilar cost may be the deciding factor in choosing a treatment or agent for formulary inclusion.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/adverse effects , Humans , Infliximab/adverse effects , Network Meta-Analysis , Treatment Outcome
16.
BMC Infect Dis ; 21(1): 156, 2021 Feb 08.
Article in English | MEDLINE | ID: covidwho-1069547

ABSTRACT

BACKGROUND: Due to the rapid spread of coronavirus disease 2019 (COVID-19) worldwide, it is necessary to ascertain essential immune inflammatory parameters that describe the severity of the disease and provide guidance for treatment. We performed network meta-analyses to determine differences in blood cells, lymphocyte subsets, and cytokines in COVID-19 patients with different clinical stages. METHODS: Databases were systematically searched to May 2, 2020, and updated on June 1, 2020. Network meta-analyses were conducted via Stata 15.0, and the mean difference (MD) and its 95% CI were used as the effect values of the pooled analysis. RESULTS: Seventy-one studies were included involving 8647 COVID-19 patients, White blood cell (WBC), neutrophil (NEUT), IL-6, and IL-10 counts increased significantly with worsening of the COVID-19, while lymphocyte (LYM) counts decreased. The levels of platelet (PLT), CD3+, CD4+, CD8+, and CD19+ cells in severe and critical patients were significantly lower than those in mild patients. IL-1ß count was significantly elevated in critical patients. CONCLUSIONS: Immune suppression and inflammatory injury play crucial roles in the progression of COVID-19, and the identification of susceptible cells and cytokines provide guidance for the early and accurate treatment of COVID-19 patients.


Subject(s)
Blood Cells , COVID-19/blood , COVID-19/immunology , Cytokines/blood , Lymphocyte Subsets , Adult , Aged , Female , Humans , Inflammation , Interleukin-10/blood , Interleukin-1beta/blood , Lymphocyte Count , Male , Middle Aged , Network Meta-Analysis , Neutrophils , Severity of Illness Index
17.
PLoS Med ; 17(12): e1003501, 2020 12.
Article in English | MEDLINE | ID: covidwho-999797

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , 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 , Azithromycin/adverse effects , Azithromycin/therapeutic use , COVID-19/mortality , COVID-19/therapy , Critical Illness , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Network Meta-Analysis , Observational Studies as Topic , Randomized Controlled Trials as Topic
18.
Public Health ; 190: 82-88, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-989090

ABSTRACT

OBJECTIVE: With the epidemic of coronavirus disease 2019 (COVID-19), the healthcare workers (HCWs) require proper respiratory personal protective equipment (rPPE) against viral respiratory infectious diseases (VRIDs). It is necessary to evaluate which type of mask and manner of wearing is the best suitable rPPE for preventing the VRID. STUDY DESIGN: A Bayesian network meta-analysis was performed to comprehensively analyze the protective efficacy of various rPPE. METHODS: This network meta-analysis protocol was registered in an international prospective register of systematic reviews (CRD42020179489). Electronic databases were searched for cluster randomized control trials (RCTs) of comparing the effectiveness of rPPE and wearing manner in preventing HCWs from VRID. The primary outcome was the incidence of laboratory-confirmed viral respiratory infection reported as an odds ratio (OR) with the associated 95% credibility interval (CrI). The secondary outcome was the incidence of clinical respiratory illness (CRI) reported as an OR with the associated 95% CrI. Surface under the cumulative ranking curve analysis (SUCRA) provided a ranking of each rPPE according to the primary outcome and the secondary outcome as data supplement. RESULTS: Six studies encompassing 12,265 HCWs were included. In terms of the incidence of laboratory-confirmed viral respiratory infection, the continuous wearing of N95 respirators (network OR, 0.48; 95% CrI: 0.27 to 0.86; SUCRA score, 85.4) showed more effective than the control group. However, in terms of reducing the incidence of CRI, there was no rPPE showing superior protective effectiveness. CONCLUSIONS: There are significant differences in preventive efficacy among current rPPE. Our result suggests that continuous wearing of N95 respirators on the whole shift can serve as the best preventive rPPE for HCWs from the VRID.


Subject(s)
COVID-19/prevention & control , Health Personnel/psychology , Masks , Personal Protective Equipment , Respiratory Protective Devices , Respiratory Tract Infections/prevention & control , Adult , Bayes Theorem , Communicable Disease Control , Humans , Network Meta-Analysis , SARS-CoV-2
19.
BMC Med ; 18(1): 402, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-979731

ABSTRACT

BACKGROUND: The increasing use of preprints to disseminate evidence on the effect of interventions for the coronavirus disease 2019 (COVID-19) can lead to multiple evidence sources for a single study, which may differ in the reported evidence. We aim to describe the proportion of evidence on the effect of interventions for COVID-19 from preprints and journal articles and map changes in evidence between and within different sources reporting on the same study. METHODS: Meta-research study. We screened the Cochrane living systematic review and network meta-analysis (COVID-NMA) database to identify all preprints and journal articles on all studies assessing interventions for COVID-19 published up to 15 August 2020. We compared all evidence sources (i.e., preprint and associated journal article) and the first and latest versions of preprints for each study to identify changes in two evidence components: study results (e.g., numeric change in hazard ratio, odds ratio, event rate, or change in p value > or < 0.05 in any outcome) and abstract conclusions (classified as positive, negative or neutral regarding the intervention effect, and as reporting uncertainty in the findings or not). Changes in study results were further classified as important changes if they (1) represented a change in any effect estimate by ≥ 10% and/or (2) led to a change in the p value crossing the threshold of 0.05. RESULTS: We identified 556 studies. In total, 338 (61%) had been reported in a preprint: 66 (20%) of these had an associated journal article (median time to publication 76 days [interquartile range (IQR) 55-106]) and 91 (27%) had > 1 preprint version. A total of 139 studies (25% of the overall sample) were reported in multiple evidence sources or versions of the same source: for 63 (45%), there was a change in at least one evidence component between or within sources (42 [30%] had a change in study results, and in 29 [21%] the change was classified as important; 33 [24%] had a change in the abstract conclusion). For studies with both a preprint and an article, a median of 29% (IQR 14-50) of total citations were attributed to the preprint instead of the article. CONCLUSIONS: Results on the effect of interventions for COVID-19 are often reported in multiple evidence sources or source versions for a single study. Evidence is not stable between and within evidence sources. Real-time linkage of all sources per study could help to keep systematic reviews up-to-date.


Subject(s)
COVID-19/therapy , Network Meta-Analysis , Preprints as Topic , Systematic Reviews as Topic , Databases, Factual , Humans , SARS-CoV-2
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