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1.
Viruses ; 14(3)2022 03 16.
Article in English | MEDLINE | ID: covidwho-1742735

ABSTRACT

Enhancing treatment uptake for hepatitis C to achieve the elimination goals set by the World Health Organization could be achieved by reducing the treatment duration. The aim of this study was to compare the sustained virological response at week 12 (SVR12) after four weeks of glecaprevir/pibrentasvir (GLE/PIB) + ribavirin compared to eight weeks of GLE/PIB and to estimate predictors for SVR12 with four weeks of treatment through a multicenter open label randomized controlled trial. Patients were randomized 2:1 (4 weeks:8 weeks) and stratified by genotype 3 and were treatment naïve of all genotypes and without significant liver fibrosis. A total of 27 patients were analyzed for predictors for SVR12, including 15 from the first pilot phase of the study. In the 'modified intention to treat' group, 100% (7/7) achieved cure after eight weeks and for patients treated for four weeks the SVR12 was 58.3% (7/12). However, patients with a baseline viral load <2 mill IU/mL had 93% SVR12. The study closed prematurely due to the low number of included patients due to the COVID-19 pandemic. Our results suggest that viral load should be taken into account when considering trials of short course treatment.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Aminoisobutyric Acids , Antiviral Agents/therapeutic use , Benzimidazoles , Cyclopropanes , Hepatitis C, Chronic/drug therapy , Humans , Lactams, Macrocyclic , Leucine/analogs & derivatives , Pandemics , Proline/analogs & derivatives , Pyrrolidines , Quinoxalines , Ribavirin/therapeutic use , Sulfonamides
2.
Environ Mol Mutagen ; 63(1): 37-63, 2022 01.
Article in English | MEDLINE | ID: covidwho-1620131

ABSTRACT

This review considers antiviral nucleoside analog drugs, including ribavirin, favipiravir, and molnupiravir, which induce genome error catastrophe in SARS-CoV or SARS-CoV-2 via lethal mutagenesis as a mode of action. In vitro data indicate that molnupiravir may be 100 times more potent as an antiviral agent than ribavirin or favipiravir. Molnupiravir has recently demonstrated efficacy in a phase 3 clinical trial. Because of its anticipated global use, its relative potency, and the reported in vitro "host" cell mutagenicity of its active principle, ß-d-N4-hydroxycytidine, we have reviewed the development of molnupiravir and its genotoxicity safety evaluation, as well as the genotoxicity profiles of three congeners, that is, ribavirin, favipiravir, and 5-(2-chloroethyl)-2'-deoxyuridine. We consider the potential genetic risks of molnupiravir on the basis of all available information and focus on the need for additional human genotoxicity data and follow-up in patients treated with molnupiravir and similar drugs. Such human data are especially relevant for antiviral NAs that have the potential of permanently modifying the genomes of treated patients and/or causing human teratogenicity or embryotoxicity. We conclude that the results of preclinical genotoxicity studies and phase 1 human clinical safety, tolerability, and pharmacokinetics are critical components of drug safety assessments and sentinels of unanticipated adverse health effects. We provide our rationale for performing more thorough genotoxicity testing prior to and within phase 1 clinical trials, including human PIG-A and error corrected next generation sequencing (duplex sequencing) studies in DNA and mitochondrial DNA of patients treated with antiviral NAs that induce genome error catastrophe via lethal mutagenesis.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , Cytidine/analogs & derivatives , DNA Damage/drug effects , Hydroxylamines/adverse effects , Nucleosides/adverse effects , SARS-CoV-2/genetics , Amides/adverse effects , Amides/therapeutic use , Antiviral Agents/therapeutic use , Cytidine/adverse effects , Cytidine/therapeutic use , Deoxyuridine/adverse effects , Deoxyuridine/analogs & derivatives , Deoxyuridine/therapeutic use , Genome, Human/drug effects , Humans , Hydroxylamines/therapeutic use , Mutagenesis/drug effects , Nucleosides/therapeutic use , Pyrazines/adverse effects , Pyrazines/therapeutic use , Ribavirin/adverse effects , Ribavirin/therapeutic use , SARS-CoV-2/drug effects
3.
Viruses ; 13(10)2021 10 14.
Article in English | MEDLINE | ID: covidwho-1470993

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body's first line of defense against invading pathogens and is induced by a variety of cellular receptors that sense viral components. However, various strategies are exploited by SARS-CoV-2 to disrupt the antiviral innate immune responses. Innate immune dysfunction is characterized by the weak generation of type I interferons (IFNs) and the hypersecretion of pro-inflammatory cytokines, leading to mortality and organ injury in patients with COVID-19. This review summarizes the existing understanding of the mutual effects between SARS-CoV-2 and the type I IFN (IFN-α/ß) responses, emphasizing the relationship between host innate immune signaling and viral proteases with an insight on tackling potential therapeutic targets.


Subject(s)
COVID-19/immunology , Immune Evasion/immunology , Immunity, Innate/immunology , Interferon Type I/immunology , SARS-CoV-2/immunology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , Cytokines/metabolism , Drug Combinations , Humans , Interferon Type I/biosynthesis , Lopinavir/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Signal Transduction/immunology
4.
J Chemother ; 34(2): 73-86, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1459998

ABSTRACT

Viral infections are particularly common among children. They often have a mild course, are self-limiting and do not need any specific treatment. However, in some cases, the disease can be severe and lead to permanent disabilities. A variety of antiviral drugs are available for the treatments of certain infectious agents: for instance, acyclovir is used to treat herpes simplex virus encephalitis. Recommendations for flu treatment may change according to the current epidemiological surveillance data, on the basis of which antiviral sensibility can be forecast: recommended drugs for the 2020-21 flu season are oseltamivir, zanamivir, peramivir and baloxavir. Some drugs are used to treat congenital infections, such as valganciclovir and ganciclovir in congenital cytomegalovirus infection. Antiretroviral prophylaxis in newborns from HIV-1 infected mothers must be initiated as soon as possible, with one or more drugs according to therapeutic regimens based on the baby's risk category. According to the most recent guidelines, antiretroviral therapy must be started at diagnosis. Several antiretroviral drugs are available today and approved for use in children, so several combinations can be made. However, out of the 29 antiretroviral drugs approved for adults, only 38% (11/29) are approved for children under the age of two and about 60% (18/29) for children under the age of twelve. Treatment with direct antiviral agents against hepatitis C virus is approved for children over the age of three; it consists in different therapeutic regimens chosen on the basis of the viral genotype (ledipasvir/sofosbuvir for genotypes 1, 4, 5 and 6, sofosbuvir/ribavirin for genotypes 2 and 3, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for all genotypes) and it has dramatically changed the course of the illness. Many molecules have been studied in order to treat SARS-CoV-2 infection, but only remdesivir seems to play a role in shortening recovery time, although inclusion criteria are very specific and data on the use in children is limited.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Adult , Antiviral Agents/therapeutic use , Child , Drug Therapy, Combination , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Humans , Infant, Newborn , Ribavirin/therapeutic use , SARS-CoV-2
5.
PLoS One ; 16(6): e0252984, 2021.
Article in English | MEDLINE | ID: covidwho-1264224

ABSTRACT

OBJECTIVES: Our study aims at comparing the efficacy and safety of IFN-based therapy (lopinavir/ritonavir, ribavirin, and interferon ß-1b) vs. favipiravir (FPV) in a cohort of hospitalized patients with non-critical COVID-19. METHODS: Single center observational study comparing IFN-based therapy (interferon ß-1b, ribavirin, and lopinavir/ritonavir) vs. FPV in non-critical hospitalized COVID-19 patients. Allocation to either treatment group was non-random but based on changes to national treatment protocols rather than physicians' selection (quasi-experimental). We examined the association between IFN-based therapy and 28-day mortality using Cox regression model with treatment as a time-dependent covariate. RESULTS: The study cohort included 222 patients, of whom 68 (28%) received IFN-based therapy. Antiviral therapy was started at a median of 5 days (3-6 days) from symptoms onset in the IFN group vs. 6 days (4-7 days) for the FPV group, P <0.0001. IFN-based therapy was associated with a lower 28-day mortality as compared to FPV (6 (9%) vs. 18 (12%)), adjusted hazard ratio [aHR] (95% Cl) = 0.27 (0.08-0.88)). No difference in hospitalization duration between the 2 groups, 9 (7-14) days vs. 9 (7-13) days, P = 0.732 was found. IFN treated group required less use of systemic corticosteroids (57%) as compared to FPV (77%), P = 0.005 after adjusting for disease severity and other confounders. Patients in the IFN treated group were more likely to have nausea and diarrhea as compared to FPV group (13%) vs. (3%), P = 0.013 and (18%) vs. (3%), P<0.0001, respectively. CONCLUSION: Early IFN-based triple therapy was associated with lower 28-days mortality as compared to FPV.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Interferon beta-1b/therapeutic use , Lopinavir/therapeutic use , Pyrazines/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Adult , Aged , Drug Therapy, Combination , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2/drug effects
6.
J Med Virol ; 93(7): 4411-4419, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1263106

ABSTRACT

In late December 2019, an outbreak of a novel coronavirus which caused coronavirus disease 2019 (COVID-19) was initiated. Acute kidney injury (AKI) was associated with higher severity and mortality of COVID-19. We aimed to evaluate the effects of comorbidities and medications in addition to determining the association between AKI, antibiotics against coinfections (AAC) and outcomes of patients. We conducted a retrospective study on adult patients hospitalized with COVID-19 in a tertiary center. Our primary outcomes were the incidence rate of AKI based on comorbidities and medications. The secondary outcome was to determine mortality, intensive care unit (ICU) admission, and prolonged hospitalization by AKI and AAC. Univariable and multivariable logistic regression method was used to explore predictive effects of AKI and AAC on outcomes. Out of 854 included participants, 118 patients developed AKI in whom, 57 used AAC and 61 did not. Hypertension and diabetes were the most common comorbidities in patients developed AKI. AAC, lopinavir/ritonavir, ribavirin, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and corticosteroids had significant higher rate of administration in patients developed AKI. AAC were associated with higher deaths (odds ratio [OR] = 5.13; 95% confidence interval (CI): 3-8.78) and ICU admission (OR = 5.87; 95%CI: 2.81-12.27), while AKI had higher OR for prolonged hospitalization (3.37; 95%CI: 1.76-6.45). Both AKI and AAC are associated with poor prognosis of COVID-19. Defining strict criteria regarding indications and types of antibiotics would help overcoming concomitant infections and minimizing related adverse events.


Subject(s)
Acute Kidney Injury/epidemiology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , SARS-CoV-2/drug effects , Acute Kidney Injury/drug therapy , Acute Kidney Injury/virology , Adult , Angiotensin-Converting Enzyme Inhibitors , Azithromycin/therapeutic use , Coinfection/drug therapy , Coinfection/prevention & control , Critical Care/statistics & numerical data , Drug Combinations , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Iran/epidemiology , Linezolid/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Treatment Outcome , Vancomycin/therapeutic use
7.
J Med Virol ; 93(5): 3176-3183, 2021 05.
Article in English | MEDLINE | ID: covidwho-1196542

ABSTRACT

This trial compared the rate and time of viral clearance in subjects receiving a combination of nitazoxanide, ribavirin, and ivermectin plus Zinc versus those receiving supportive treatment. This non-randomized controlled trial included 62 patients on the triple combination treatment versus 51 age- and sex-matched patients on routine supportive treatment. all of them confirmed cases by positive reverse-transcription polymerase chain reaction of a nasopharyngeal swab. Trial results showed that the clearance rates were 0% and 58.1% on the 7th day and 13.7% and 73.1% on the 15th day in the supportive treatment and combined antiviral groups, respectively. The cumulative clearance rates on the 15th day are 13.7% and 88.7% in the supportive treatment and combined antiviral groups, respectively. This trial concluded by stating that the combined use of nitazoxanide, ribavirin, and ivermectin plus zinc supplement effectively cleared the SARS-COV2 from the nasopharynx in a shorter time than symptomatic therapy.


Subject(s)
COVID-19/drug therapy , Ivermectin/therapeutic use , Nitro Compounds/therapeutic use , Ribavirin/therapeutic use , SARS-CoV-2 , Thiazoles/therapeutic use , Zinc/therapeutic use , Adult , Antimetabolites/administration & dosage , Antimetabolites/therapeutic use , Antiparasitic Agents/administration & dosage , Antiparasitic Agents/therapeutic use , Female , Humans , Ivermectin/administration & dosage , Male , Nitro Compounds/administration & dosage , Ribavirin/administration & dosage , Thiazoles/administration & dosage , Trace Elements/administration & dosage , Trace Elements/therapeutic use , Zinc/administration & dosage
8.
BMJ Case Rep ; 14(3)2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1153655

ABSTRACT

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.


Subject(s)
Coinfection/therapy , Coinfection/virology , Hepatitis C, Chronic/therapy , Hepatitis, Autoimmune/therapy , Plasmapheresis/methods , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/therapy , Drug Therapy, Combination , Female , Hepatitis C, Chronic/complications , Hepatitis, Autoimmune/complications , Humans , Interferon alpha-2/therapeutic use , Middle Aged , Polyethylene Glycols/therapeutic use , Positive-Strand RNA Viruses/isolation & purification , Ribavirin/therapeutic use , SARS-CoV-2 , Treatment Outcome , Viral Load
10.
J Infect Chemother ; 27(6): 876-881, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1091770

ABSTRACT

INTRODUCTION: Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. METHODS: A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. RESULTS: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63-1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. CONCLUSIONS: In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.


Subject(s)
COVID-19/drug therapy , Ribavirin , Aged , China , Female , Humans , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use , Treatment Outcome
11.
Arch Microbiol ; 203(5): 2043-2057, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1068711

ABSTRACT

The Covid-19 pandemic is highly contagious and has spread rapidly across the globe. To date there have been no specific treatment options available for this life-threatening disease. During this medical emergency, target-based drug repositioning/repurposing with a continuous monitoring and recording of results is an effective method for the treatment and drug discovery. This review summarizes the recent findings on COVID-19, its genomic organization, molecular evolution through phylogenetic analysis and has recapitulated the drug targets by analyzing the viral molecular machinery as drug targets and repurposing of most frequently used drugs worldwide and their therapeutic applications in COVID-19. Data from solidarity trials have shown that the treatment with Chloroquine, hydroxychloroquine and lopinavir-ritonavir had no effect in reducing the mortality rate and also had adverse side effects. Remdesivir, Favipiravir and Ribavirin might be a safer therapeutic option for COVID-19. Recent clinical trial has revealed that dexamethasone and convalescent plasma treatment can reduce mortality in patients with severe forms of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Drug Repositioning , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Animals , Chloroquine/therapeutic use , Dexamethasone/therapeutic use , Evolution, Molecular , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Pandemics , Phylogeny , Prospective Studies , Pyrazines/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use
12.
Monaldi Arch Chest Dis ; 90(4)2020 Dec 03.
Article in English | MEDLINE | ID: covidwho-1060428

ABSTRACT

The index case of COVID-19 in Sabzevar, Khorasan Razavi Province in northeastern Iran, was an 80-year-old man with a history of psycho-neurological illness and acute respiratory clinical symptoms, and a history of travel to areas with confirmed COVID-19 cases in Gorgan City. He was identified on February 16, 2020, and his laboratory diagnosis was made on February 26, 2020. The patient was hospitalized and discharged after complete recovery. The contacts of the patient were traced, revealing the infection of his 30-year-old son with milder symptoms of COVID-19, which was confirmed through a laboratory test on April 4, 2020 and was recommended for home quarantine. Other family members had no signs of COVID-19.


Subject(s)
COVID-19/diagnosis , COVID-19/transmission , SARS-CoV-2/genetics , Adult , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Contact Tracing/methods , Drug Therapy, Combination , Humans , Iran/epidemiology , Male , Quarantine/methods , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/virology , Ribavirin/administration & dosage , Ribavirin/therapeutic use , Tomography, X-Ray Computed/methods , Travel-Related Illness , Treatment Outcome , Vancomycin/administration & dosage , Vancomycin/therapeutic use
13.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1030457

ABSTRACT

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Amides/pharmacology , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/pharmacology , Azetidines/therapeutic use , Chloroquine/pharmacology , Chloroquine/therapeutic use , Drug Combinations , Humans , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Immunization, Passive , Indoles/pharmacology , Indoles/therapeutic use , Interferons/pharmacology , Interferons/therapeutic use , Ivermectin/pharmacology , Ivermectin/therapeutic use , Lopinavir/pharmacology , Lopinavir/therapeutic use , Nitro Compounds , Oseltamivir/pharmacology , Oseltamivir/therapeutic use , Purines/pharmacology , Purines/therapeutic use , Pyrazines/pharmacology , Pyrazines/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Ribavirin/pharmacology , Ribavirin/therapeutic use , Ritonavir/pharmacology , Ritonavir/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thiazoles/pharmacology , Thiazoles/therapeutic use
14.
Pharmacol Res Perspect ; 9(1): e00705, 2021 02.
Article in English | MEDLINE | ID: covidwho-1014102

ABSTRACT

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , SARS-CoV-2 , Animals , Antibodies, Monoclonal, Humanized/therapeutic use , Chloroquine/therapeutic use , Drug Interactions , Humans , Lopinavir/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use
15.
Adv Chronic Kidney Dis ; 27(5): 434-441, 2020 09.
Article in English | MEDLINE | ID: covidwho-975046

ABSTRACT

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Renal Insufficiency, Chronic/metabolism , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/prevention & control , COVID-19/therapy , COVID-19 Vaccines/therapeutic use , Chloroquine/therapeutic use , Creatinine/metabolism , Cytidine/analogs & derivatives , Cytidine/therapeutic use , Dexamethasone/therapeutic use , Drug Combinations , Drug Interactions , Humans , Hydroxychloroquine/therapeutic use , Hydroxylamines/therapeutic use , Immunization, Passive , Interferons/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Lopinavir/therapeutic use , Pyrazines/therapeutic use , Renal Elimination , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Renal Replacement Therapy , Ribavirin/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2
16.
Eur Rev Med Pharmacol Sci ; 24(22): 11977-11981, 2020 11.
Article in English | MEDLINE | ID: covidwho-962034

ABSTRACT

Researchers have found many similarities between the 2003 severe acute respiratory syndrome (SARS) virus and SARS-CoV-19 through existing data that reveal the SARS's cause. Artificial intelligence (AI) learning models can be created to predict drug structures that can be used to treat COVID-19. Despite the effectively demonstrated repurposed drugs, more repurposed drugs should be recognized. Furthermore, technological advancements have been helpful in the battle against COVID-19. Machine intelligence technology can support this procedure by rapidly determining adequate and effective drugs against COVID-19 and by overcoming any barrier between a large number of repurposed drugs, laboratory/clinical testing, and final drug authorization. This paper reviews the proposed vaccines and medicines for SARS-CoV-2 and the current application of AI in drug repurposing for COVID-19 treatment.


Subject(s)
Artificial Intelligence , COVID-19/drug therapy , Drug Development , Drug Repositioning , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Ascorbic Acid/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Chloroquine/therapeutic use , Deep Learning , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Lopinavir/therapeutic use , Machine Learning , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Vitamins/therapeutic use
17.
Trials ; 21(1): 999, 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-958044

ABSTRACT

OBJECTIVES: A severe epidemic of COVID-19 has broken out in China and has become a major global public health event. We focus on the Acute Respiratory Distress Syndrome (ARDS)-like changes and overactivation of Th17 cells (these produce cytokines) in patients with COVID-19. We aim to explore the safety and efficacy of ixekizumab (an injectable drug for the treatment of autoimmune diseases) to prevent organ injury caused by the immune response to COVID-19. Ixekizumab is a human monoclonal antibody that binds to interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. TRIAL DESIGN: The experiment is divided into two stages. In the first stage, the open trial, 3 patients with COVID-19 are treated with ixekizumab, and the safety and efficacy are observed for 7 days. In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. This is a two-center, open-label, randomized controlled pilot trial with 2-arm parallel group design (1:1 ratio). PARTICIPANTS: Patients with COVID-19 aged 18-75 with increased Interleukin (IL)-6 levels will be enrolled, but patients with severe infections requiring intensive care will be excluded. The trial will be undertaken in two centers. The first stage is carried out in Xiangya Hospital of Central South University, and the second stage is carried out simultaneously in the Third Xiangya Hospital of Central South University. INTERVENTION AND COMPARATOR: In the first stage, three subjects are given ixekizumab ("Taltz") (80 mg/ml, 160 mg as a single hypodermic injection) and antiviral therapy (α-interferon (administer 5 million U by aerosol inhalation twice daily), lopinavir/ritonavir (administer 100mg by mouth twice daily, for the course of therapy no more than 10 days), chloroquine (administer 500mg by mouth twice daily, for the course of therapy no more than 10 days), ribavirin (administer 500mg by intravenous injection two to three times a day, for the course of therapy no more than 10 days), or arbidol (administer 200mg by mouth three times a day, for the course of therapy no more than 10 days), but not more than 3 types). The treatment course of the first stage is 7 days. In the second stage, 40 randomized patients will receive the following treatments--Group 1: ixekizumab (80 mg/ml, 160 mg as a single hypodermic injection) with antiviral therapy (the same scheme as in the first stage); Group 2: antiviral therapy alone (the same scheme as in the first stage). The length of the second treatment course is 14 days. MAIN OUTCOMES: The primary outcome is a change in pulmonary CT severity score (an imaging tool for assessing COVID-19, which scores on the basis of all abnormal areas involved). Pulmonary CT severity score is assessed on the 7th day, 14th day, or at discharge. RANDOMISATION: In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. The eLite random system of Nanjing Medical University is used for randomization. BLINDING (MASKING): The main efficacy indicator, the CT results, will be evaluated by the third-party blinded and independent research team. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): In the second stage, 40 patients with COVID-19 are randomly divided into two groups at 1:1 for 14 days. TRIAL STATUS: Trial registration number is ChiCTR2000030703 (version 1.7 as of March 19, 2020). The recruitment is ongoing, and the date recruitment was initiated in June 2020. The anticipated date of the end of data collection is June 2021. TRIAL REGISTRATION: The name of the trial register is the Chinese Clinical Trial Registry. The trial registration number is ChiCTR2000030703 ( http://www.chictr.org.cn/ ). The date of trial registration is 10 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/drug effects , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/pharmacology , Antimalarials/administration & dosage , Antimalarials/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Case-Control Studies , China/epidemiology , Chloroquine/administration & dosage , Chloroquine/therapeutic use , Drug Therapy, Combination , Humans , Indoles/administration & dosage , Indoles/therapeutic use , Interleukin-17/immunology , Lopinavir/administration & dosage , Lopinavir/therapeutic use , Middle Aged , Ribavirin/administration & dosage , Ribavirin/therapeutic use , Ritonavir/administration & dosage , Ritonavir/therapeutic use , SARS-CoV-2/genetics , Safety , Th17 Cells/immunology , Treatment Outcome
19.
J Med Virol ; 92(10): 2205-2208, 2020 10.
Article in English | MEDLINE | ID: covidwho-935121

ABSTRACT

Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID-19 patients. A higher frequency of pulmonary embolism (PE) than expected in COVID-19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID-19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID-19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID-19 may be related to PE and not necessarily always due to the parenchymal disease.


Subject(s)
COVID-19/complications , Pulmonary Embolism/complications , Respiratory Distress Syndrome/complications , SARS-CoV-2/pathogenicity , Acute Disease , Aged , Biomarkers/blood , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/diagnostic imaging , COVID-19/drug therapy , COVID-19/virology , Ceftazidime/therapeutic use , Dyspnea/physiopathology , Fibrin Fibrinogen Degradation Products/metabolism , Heparin/therapeutic use , Humans , Hypoxia/physiopathology , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Methylprednisolone/therapeutic use , Middle Aged , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Pulmonary Embolism/virology , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/virology , Ribavirin/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome
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