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Clinical Microbiology and Infection :... Aug 2020Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics. (Review)
Review
BACKGROUND
Repurposing hydroxychloroquine (HCQ) and chloroquine (CQ) as antiviral agents is a re-emerging topic with the advent of new viral epidemics.
AIMS
To summarize evidence from human clinical studies for using HCQ or CQ as antiviral agents for any viral infection.
SOURCES
PubMed, EMBASE, Scopus, Web of Science for published studies without time or language restrictions; Cochrane Clinical Trial Registry and Chinese Clinical Trials Registry for trials registered after 2015; MedRxiv for preprints within the last 12 months.
CONTENT
Study eligibility criteria were interventional and prospective observational studies (with or without a control group). Participants were adults and children with a confirmed viral infection. Interventions included the use of CQ or HCQ as antiviral agent in one or more groups of the study. Two authors independently screened abstracts, and all authors agreed on eligible studies. A meta-analysis was planned if studies were available which were similar in terms of participants, intervention, comparator and outcomes. Nineteen studies (including two preprints) were eligible (HIV 8, HCV 2, dengue 2, chikungunya 1, COVID-19 6). Nine and ten studies assessed CQ and HCQ respectively. Benefits of either drug for viral load suppression in HIV are inconsistent. CQ is ineffective in curing dengue (high-certainty evidence) and may have little or no benefit in curing chikungunya (low-certainty evidence). The evidence for COVID-19 infection is rapidly evolving but at this stage we are unsure whether either CQ or HCQ has any benefit in clearing viraemia (very-low-certainty evidence).
IMPLICATIONS
Using HCQ or CQ for HIV/HCV infections is now clinically irrelevant as other effective antivirals are available for viral load suppression (HIV) and cure (HCV). There is no benefit of CQ in dengue, and the same conclusion is likely for chikungunya. More evidence is needed to confirm whether either HCQ or CQ is beneficial in COVID-19 infection.
Topics: Adult; Antiviral Agents; Betacoronavirus; COVID-19; Child; Chloroquine; Clinical Trials as Topic; Coronavirus Infections; Drug Repositioning; Humans; Hydroxychloroquine; Observational Studies as Topic; Pandemics; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Viral Load
PubMed: 32470568
DOI: 10.1016/j.cmi.2020.05.016 -
European Review For Medical and... Sep 2020In December 2019, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection broke out in Wuhan, China. However, we still lack a comprehensive understanding...
OBJECTIVE
In December 2019, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection broke out in Wuhan, China. However, we still lack a comprehensive understanding of this emerging virus. In this manuscript, we collected relevant articles and reviewed the characteristics about SARS-CoV-2.
MATERIALS AND METHODS
We performed an online search on PubMed and Web of Science with the keywords COVID-19, 2019-nCoV and SARS-CoV-2, and summarized the epidemiology, virology, clinical features and treatments of SARS-CoV-2 infection.
RESULTS
We retrieved 157 published papers about SARS-CoV-2 from January, 2020 to April, 2020. We found that SARS-CoV-2 was a kind of virus with low mortality rate and high infectivity. This virus can enter human cells through angiotensin-converting enzyme 2 (ACE2) in alveoli and activate immune response in human body. SARS-CoV-2 infection can be classified as asymptomatic, mild, common, severe, and critical. We summarized antiviral drugs against SARS-CoV-2, such as remdesivir, hydroxychloroquine and favipiravir. Because the vaccine of SARS-CoV-2 is developing, more clinical studies are needed to verify the safety and efficacy of these treatments.
CONCLUSIONS
SARS-CoV-2 is a novel coronavirus that has caused a global pandemic. We should pay more attention to prevent SARS-CoV-2 and try to control it sooner.
Topics: Adenosine Monophosphate; Alanine; Angiotensin-Converting Enzyme 2; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Extracorporeal Membrane Oxygenation; Glucocorticoids; Humans; Immunization, Passive; Immunotherapy; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2
PubMed: 32965016
DOI: 10.26355/eurrev_202009_22873 -
PLoS Neglected Tropical Diseases Jun 2022Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients.
METHODS
The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I2). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger's test.
RESULTS
We identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMD<-0.5) and significantly (P<0.05) associated mortality: thrombin time (TT) (SMD = 1.53), viral load (SMD = 1.47), activated partial-thromboplastin time (APTT) (SMD = 1.37), aspartate aminotransferase (AST) (SMD = 1.19), lactate dehydrogenase (LDH) (SMD = 1.13), platelet count (PLT) (SMD = -0.47), monocyte percentage (MON%) (SMD = -0.47), lymphocyte percentage (LYM%) (SMD = -0.46) and albumin (ALB) (SMD = -0.43). Alanine aminotransferase, AST, creatin phosphokinase, LDH, PLT, partial-thromboplastin time and viral load contributed to the risk of dying of SFTS patients in each subgroup analyses. Sensitivity analysis demonstrated that the results above were robust.
CONCLUSIONS/SIGNIFICANCE
The abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.
Topics: Antiviral Agents; Bunyaviridae Infections; Humans; Laboratories, Clinical; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Thromboplastin; Viral Load
PubMed: 35714138
DOI: 10.1371/journal.pntd.0010489 -
International Journal of Antimicrobial... Mar 2024This study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19).
METHODS
Seven databases were searched from their inception to 01 June 2023. The risk of bias in randomised controlled trials and retrospective studies was evaluated individually using the Cochrane risk-of-bias tool and Newcastle Ottawa Scale.
RESULTS
In total, 160 studies involving 933 409 COVID-19 patients were evaluated. Compared with placebo or standard of care, proxalutamide demonstrated remarkable efficacy in reducing mortality rates, hospitalisation rates, serious adverse events, and the need for mechanical ventilation. Furthermore, it significantly enhanced both the rate of clinical improvement and expedited the duration of clinical recovery when compared with control groups. In patients with mild-to-moderate COVID-19, proxalutamide exhibited the above advantages, except for mortality reduction. Triazavirin was the most effective treatment for reducing the time required for viral clearance and improving the discharge rate. Leritrelvir and VV116 were ranked first in terms of enhancing the viral clearance rate on days 7 and 14, respectively. Molnupiravir was the most effective treatment for reducing the need for oxygen support. Overall, these findings remained consistent across the various subgroups.
CONCLUSIONS
A thorough evaluation of effectiveness, applicable to both mild-to-moderate and unstratified populations, highlights the specific advantages of proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 in combating COVID-19. Additional clinical data are required to confirm the efficacy and safety of simnotrelvir/ritonavir and leritrelvir. The safety profiles of these antivirals were deemed acceptable.
Topics: Humans; Network Meta-Analysis; COVID-19; Retrospective Studies; Ritonavir; Antiviral Agents; Cytidine; Hydroxylamines
PubMed: 38244811
DOI: 10.1016/j.ijantimicag.2024.107096 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
Fundamental & Clinical Pharmacology Apr 2021Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed... (Meta-Analysis)
Meta-Analysis Review
Viral infections remain a major cause of economic loss with an unmet need for novel therapeutic agents. Ivermectin is a putative antiviral compound; the proposed mechanism is the inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importins, a necessary process for propagation of infections. We systematically reviewed the evidence for the applicability of ivermectin against viral infections including SARS-CoV-2 regarding efficacy, mechanisms and selective toxicity. The SARS-CoV-2 genome was mined to determine potential nuclear location signals for ivermectin and meta-analyses for in vivo studies included all comparators over time, dose range and viral replication in multiple organs. Ivermectin inhibited the replication of many viruses including those in Flaviviridae, Circoviridae and Coronaviridae families in vitro. Real and mock nuclear location signals were identified in SARS-CoV-2, a potential target for ivermectin and predicting a sequestration bait for importin β, stopping infected cells from reaching a virus-resistant state. While pharmacokinetic evaluations indicate that ivermectin could be toxic if applied based on in vitro studies, inhibition of viral replication in vivo was shown for Porcine circovirus in piglets and Suid herpesvirus in mice. Overall standardized mean differences and 95% confidence intervals for ivermectin versus controls were -4.43 (-5.81, -3.04), p < 0.00001. Based on current results, the potential for repurposing ivermectin as an antiviral agent is promising. However, further work is needed to reconcile in vitro studies with clinical efficacy. Developing ivermectin as an additional antiviral agent should be pursued with an emphasis on pre-clinical trials in validated models of infection.
Topics: Animals; Anthelmintics; Antiviral Agents; Computer Simulation; Drug Repositioning; Humans; Ivermectin; SARS-CoV-2; Swine; COVID-19 Drug Treatment
PubMed: 33427370
DOI: 10.1111/fcp.12644 -
Frontiers in Public Health 2023Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making.
METHODS
We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods.
RESULTS
Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients.
CONCLUSION
The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.
Topics: Humans; Male; Antiviral Agents; Network Meta-Analysis; Hepacivirus; Bayes Theorem; Hepatitis C, Chronic; Treatment Outcome; Ritonavir; Hepatitis C; Kidney Failure, Chronic
PubMed: 37841743
DOI: 10.3389/fpubh.2023.1179531 -
Reviews in Medical Virology May 2022Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking... (Review)
Review
Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking resistance against therapeutics currently under development. Since 2015, the field of RSV molecular epidemiology has evolved rapidly with around 20-30 published articles per year. The objective of this systematic review is to identify knowledge gaps in recent RSV genetic literature to guide global molecular epidemiology research. We included 78 studies published between 2015 and 2020 describing 12,998 RSV sequences of which 8,233 (63%) have been uploaded to GenBank. Seventeen (22%) studies were performed in low- and middle-income countries (LMICs), and seven (9%) studies sequenced whole-genomes. Although most reported polymorphisms for monoclonal antibodies in clinical development (nirsevimab, MK-1654) have not been tested for resistance in neutralisation essays, known resistance was detected at low levels for the nirsevimab and palivizumab binding site. High resistance was found for the suptavumab binding site. We present the first literature review of an enormous amount of RSV genetic data. The need for global monitoring of RSV molecular epidemiology becomes increasingly important in evaluating the effectiveness of monoclonal antibody candidates as they reach their final stages of clinical development. We have identified the following three knowledge gaps: whole-genome data to study global RSV evolution, data from LMICs and data from global surveillance programs.
Topics: Antibodies, Monoclonal; Antiviral Agents; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34543489
DOI: 10.1002/rmv.2284 -
Antiviral Research Jan 2023The alphaviruses are a widely distributed group of positive-sense, single stranded, RNA viruses. These viruses are largely arthropod-borne and can be found on all... (Review)
Review
The alphaviruses are a widely distributed group of positive-sense, single stranded, RNA viruses. These viruses are largely arthropod-borne and can be found on all populated continents. These viruses cause significant human disease, and recently have begun to spread into new populations, such as the expansion of Chikungunya virus into southern Europe and the Caribbean, where it has established itself as endemic. The study of alphaviruses is an active and expanding field, due to their impacts on human health, their effects on agriculture, and the threat that some pose as potential agents of biological warfare and terrorism. In this systematic review we will summarize both historic knowledge in the field as well as recently published data that has potential to shift current theories in how alphaviruses are able to function. This review is comprehensive, covering all parts of the alphaviral life cycle as well as a brief overview of their pathology and the current state of research in regards to vaccines and therapeutics for alphaviral disease.
Topics: Humans; Antiviral Agents; Virus Replication; Chikungunya virus; Alphavirus Infections; Caribbean Region
PubMed: 36436722
DOI: 10.1016/j.antiviral.2022.105476 -
Frontiers in Cellular and Infection... 2023Nearly 30%-40% of patients with chronic hepatitis B do not fall into any of the traditional natural history classification and thus are classified as indeterminate.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nearly 30%-40% of patients with chronic hepatitis B do not fall into any of the traditional natural history classification and thus are classified as indeterminate. However, it is unclear whether patients in the indeterminate phase (IP) are at a higher risk for hepatocellular carcinoma (HCC) than those in the defined phases (DP) and would benefit from antiviral therapy. We performed a systematic review and meta-analysis of HCC incidence and HBsAg clearance among patients in the IP versus DP.
METHODS
We defined the clinical phases as per the AASLD 2018 hepatitis B guidance. We searched PubMed, Embase, Medline, and Web of Science for relevant studies that reported HCC incidence or HBsAg clearance in IP versus DP patients published between January 2007 and March 2023. Annual HCC incidence and HBsAg clearance rates were pooled using a random/common-effects model.
RESULTS
We analyzed data from 14 studies, comprising 7798 IP patients (222 patients developed HCC and 239 achieved HBsAg clearance) and 10,725 DP patients. The pooled annual HCC incidence was 2.54 cases per 1,000 person-years (95% CI, 1.14-4.39) and HBsAg clearance rate was 12.36 cases per 1,000 person-years (95% CI, 10.70-14.13) for the IP patients. IP patients were associated with significantly higher HCC incidence risk (RR = 1.64, 95% CI, 1.34-2.00) and slightly lower annual HBsAg clearance rate (RR = 0.83, 95% CI, 0.70-0.99) than the DP patients. In addition, HBeAg-negative IP patients (2.31%; 95% CI, 0.87-4.45) showed a significantly higher HCC incidence than those who were HBeAg positive (0.00%; 95% CI, 0.00-0.99) (< 0.001). The Asia-Pacific region IP patients (4.30%; 95% CI, 2.07-7.27) were also associated with a higher HCC incidence versus Europe (0.05%; 95% CI, 0.00-1.39) (< 0.001). However, there were no significant differences between different strategies (treated vs. untreated: 2.56%; 95% CI, 1.01-4.63 vs. 1.61%; 95% CI, 0.00-5.81, = 0.09), and heterogeneity was substantial across the studies ( 89%).
CONCLUSION
The systematic review and meta-analysis showed a high HCC incidence and low HBsAg clearance among patients in the IP, especially for HBeAg-negative patients and the Asian population. We emphasize that future multicenter prospective cohort studies or randomized trials are needed to verify if expanding antiviral therapy for patients in the IP is associated with reduced HCC risk or good treatment outcomes.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Liver Neoplasms; Hepatitis B e Antigens; Incidence; Prospective Studies; Hepatitis B; Hepatitis B virus; Antiviral Agents; Multicenter Studies as Topic
PubMed: 37771696
DOI: 10.3389/fcimb.2023.1226755