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Publication
Journal: World Journal of Hepatology
January/23/2022
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.
Keywords: COVID-19 treatment; COVID-19 vaccine; Chronic liver disease; Gastrointestinal side effects; Hepatic side effects; Liver transplantation.
Publication
Journal: Ginekologia Polska
January/23/2022
Abstract
Objectives: The current study aimed to describe the incidence of abnormal liver function tests (LFTs) in pregnant COVID-19 patients, explore the association between LFTs with current medication, and provide a reference for medical therapy of pregnant patients with COVID-19.
Material and methods: This retrospective single tertiary center cohort study included 122 pregnant patients with confirmed COVID-19 admitted and treated from April 1, 2020, to May 31, 2020. We defined abnormal LFTs as the elevation of the following liver enzymes in serum per our hospital's laboratory reference range standards: AST > 35 U/L, ALT > 35 U/L, and TBIL > 1.2 mg/dL. We evaluated patients for demographic and clinical features, laboratory parameters, medications, and hospital length of stay (LOS).
Results: Patients in this cohort had clinical presentations of fever (84.4%), dry cough (78.6%), and shortness of breathing (6.5%). In total, 17 (13.9%) patients had abnormal LFTs during hospitalization. Critically ill patients were three-fold higher in the abnormal LFTs group (11.8%) than in the normal LFTs group (3.8%, p = 0.16). The proportion of patients who used hydroxychloroquine and lopinavir/ritonavir were significantly higher in patients with abnormal LFTs (88.2% and 35.3%, respectively) than those with normal LFTs (62.9% and 15.2%, p = 0.04 and p = 0.04, respectively). The hospital length of stay (LOS) was significantly longer in the abnormal LFTs group (8.2 ± 5.8 days) than in the normal LFT group (6.0 ± 2.8 days, p = 0.02).
Conclusions: SARS-CoV-2 may induce liver injury and the LFT abnormality was generally mild in pregnant patients with COVID-19. Abnormal LFTs are associated with prolonged hospital LOS. Drug use was the most crucial risk factor for liver injury during hospitalization. The use of lopinavir/ritonavir and hydroxychloroquine were significantly higher, and the course of treatment of these drugs was significantly longer in pregnant women with abnormal LFTs than the patients with normal LFTs. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating LFTs.
Keywords: COVID-19; SARS-CoV-2; liver function test; pregnancy.
Publication
Journal: Biology
January/20/2022
Abstract
(1) Background: The antiviral treatment for COVID-19 disease started to be largely used in 2020 and has been found to be efficient, although it is not specific for SARS-CoV-2 virus. There were some concerns that it may produce liver damage or other side effects. (2) Methods: The aim of this study was to observe if antiviral therapy is affecting liver parameters or producing other side-effects in patients hospitalized for COVID-19 disease. The study included a group of patients hospitalized in the internal medicine department of Oradea Municipal Clinical Hospital, Romania, between August 2020-June 2021, diagnosed with SARS-CoV-2 viral infection by RT-PCR method or rapid antigen test. During hospitalization, patients were treated with a Lopinavir/Ritonavir (Kaletra) combination, or with Favipiravir or Remdesivir. In addition to monitoring the evolution of the disease (clinical and biochemical), also hepatic parameters were analyzed at admission, during hospitalization, and at discharge. (3) Results: In the group of studied patients, the mean value of aspartat aminotrensferase did not increase above normal at discharge, alanin aminotransferase increased, but below twice the normal values, and cholestasis registered a statistically insignificant slight increase. (4) Conclusions: In our study, we found that all three antivirals were generally well tolerated and their use did not alter liver function in a significant manner.
Keywords: COVID-19; antivirals; coronavirus; hepatic parameters.
Publication
Journal: Diabetes and Metabolic Syndrome: Clinical Research and Reviews
January/19/2022
Abstract
Background and aims: Molnupiravir is a newer oral antiviral drug that has recently received emergency use authorization (EUA) in USA, UK and India. We aim to conduct an update on our previous systematic review to provide practical clinical guideline for using molnupiravir in patients with COVID-19.
Methods: We systematically searched the electronic database of PubMed, MedRxiv and Google Scholar until January 5, 2022, using key MeSH keywords.
Results: Final result of phase 3 study in 1433 non-hospitalized COVID-19 patients showed a significant reduction in composite risk of hospital admission or death (absolute risk difference, -3.0% [95% confidence interval {CI}, -5.9 to -0.1%]; 1-sided P = 0.02) although with a non-significant 31% relative risk reduction (RRR). RRR for death alone was 89% (95% CI, 14 to 99; P-value not reported). Number needed to treat to prevent 1 death or 1 hospitalization or death composite appears to be closely competitive to other agents having EUA in people with COVID-19. However, cost-wise molnupiravir is comparatively cheaper compared to all other agents.
Conclusion: Molnupiravir could be a useful agent in non-pregnant unvaccinated adults with COVID-19 who are at increased risk of severity including hospitalization. However, it is effective only when used within 5-days of onset of symptoms. A 5-days course seems to be safe without any obvious short-term side effects.
Keywords: Bamlanivimab–etesevimab; COVID-19; Casirivimab–imdevimab; Molnupiravir; Nirmatrelvir-ritonavir; Remdesivir; SARS-CoV-2; Sotrovimab.
Publication
Journal: World Journal of Gastroenterology
January/19/2022
Abstract
Background: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory symptoms. While gastrointestinal (GI) manifestations either at presentation or during hospitalization are also common, their impact on clinical outcomes is controversial. Some studies have described worse outcomes in COVID-19 patients with GI symptoms, while others have shown either no association or a protective effect. There is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes, including mortality and disease severity.
Aim: To investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical outcomes.
Methods: We retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15, 2020. GI symptoms were recorded at admission and during hospitalization. Demographic, clinical, laboratory, and treatment data were retrieved. Clinical outcomes included all-cause mortality, disease severity at presentation, need for intensive care unit (ICU) admission, development of acute respiratory distress syndrome, and need for mechanical ventilation. Multivariate logistic regression model was used to identify independent predictors of the adverse outcomes.
Results: The prevalence of any GI symptom at admission was 27.1% and during hospitalization was 19.8%. The most common symptoms were nausea (98 patients), diarrhea (76 patients), vomiting (73 patients), and epigastric pain or discomfort (69 patients). There was no difference in the mortality between the two groups (6.21% vs 5.5%, P = 0.7). Patients with GI symptoms were more likely to have severe disease at presentation (33.13% vs 22.5%, P < 0.001) and prolonged hospital stay (15 d vs 14 d, P = 0.04). There was no difference in other clinical outcomes, including ICU admission, development of acute respiratory distress syndrome, or need for mechanical ventilation. Drugs associated with the development of GI symptoms during hospitalization were ribavirin (diarrhea 26.37% P < 0.001, anorexia 17.58%, P = 0.02), hydroxychloroquine (vomiting 28.52%, P = 0.009) and lopinavir/ritonavir (nausea 32.65% P = 0.049, vomiting 31.47% P = 0.004, and epigastric pain 12.65% P = 0.048). In the multivariate regression analysis, age > 65 years was associated with increased mortality risk [odds ratio (OR) 7.53, confidence interval (CI): 3.09-18.29, P < 0.001], ICU admission (OR: 1.79, CI: 1.13-2.83, P = 0.012), and need for mechanical ventilation (OR: 1.89, CI:1.94-2.99, P = 0.007). Hypertension was an independent risk factor for ICU admission (OR: 1.82, CI:1.17-2.84, P = 0.008) and need for mechanical ventilation (OR: 1.66, CI: 1.05-2.62, P = 0.028).
Conclusion: Patients with GI symptoms are more likely to have severe disease at presentation; however, mortality and disease progression is not different between the two groups.
Keywords: COVID-19; Disease severity; Gastrointestinal manifestations; Intensive care unit admission; Mechanical ventilation; Mortality.
Publication
Journal: Current Drug Discovery Technologies
January/17/2022
Abstract
Background: Drug discovery and development process is an expensive, complex, time-consuming and risky. There are different techniques involved in the drug development process which include random screening, computational approach, molecular manipulation and serendipitous research. Among these methods, the computational approach is considered as an efficient strategy to accelerate and economize the drug discovery process.
Objective: This approach is mainly applied in various phases of drug discovery process including target identification, target validation, lead identification and lead optimization. Due to increase in the availability of information regarding various biological targets of different disease states, computational approaches such as molecular docking, de novo design, molecular similarity calculation, virtual screening, pharmacophore-based modeling and pharmacophore mapping have been applied extensively.
Methods: Various drug molecules can be designed by applying computational tools to explore the drug candidates for treatment of Coronavirus infection. The world health organization has announced the novel corona virus disease as COVID-19 and declared it as pandemic globally on 11 February 2020. So, it is thought of interest to scientific community to apply computational methods to design and optimize the pharmacological properties of various clinically available and FDA approved drugs such as remdesivir, ribavirin, favipiravir, oseltamivir, ritonavir, arbidol, chloroquine, hydroxychloroquine, carfilzomib, baraticinib, prulifloxacin, etc for effective treatment of COVID-19 infection.
Results: Further, various survey reports suggest that the extensive studies are carried out by various research communities to find out the safety and efficacy profile of these drug candidates.
Conclusion: This review is focused on the study of various aspects of these drugs related to their target sites on virus, binding interactions, physicochemical properties etc.
Keywords: Electrochemical biosensor; Regular Prussian blue nanocrystal; Graphene oxide; High sensitivity; Uric acid; Uricase.
Publication
Journal: Journal of Cardiovascular Pharmacology and Therapeutics
January/9/2022
Abstract
Background: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population.
Methods: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms).
Results: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test).
Conclusion: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.
Keywords: COVID-19; QTc; SARS-CoV-2; critically ill; prolongation.
Publication
Journal: Drug Resistance Updates
January/6/2022
Abstract
The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.
Keywords: Baricitinib; COVID-19; Casirivimab; Dexamethasone; Imdevimab; Omicron; Paxlovid; Remdesivir; SARS-CoV-2; Sotrovimab; Tocilizumab.
Publication
Journal: Frontiers in Bioscience - Landmark
January/6/2022
Abstract
Thousands of drugs, nutraceuticals and their combinations can be used to select candidate therapeutics for targeting SARS-CoV-2 and its symptoms in order to curb COVID-19. A comprehensive, multi-level strategy against COVID-19 should include drug targeting of biomolecules and biochemical pathways involved in the prevention and proliferation of the infection, and the fatal or serious symptoms following infection. Several drugs are routinely used in the treatment of different categories of seriously ill COVID-19 patients including tocilizumab, remdesivir and dexamethasone. The current risk/benefit assessment supports the emergency testing and approval of more drugs. The process for new drug selection could be based on the identification of one drug for one target, or of a multi-potent drug for many targets and drug combinations for one or more targets, that can cause a substantial reduction in the high mortality rate of COVID-19. Several drugs have been identified that can fit this potential role by targeting different stages of COVID-19 including baricitinib, molnupiravir and PF-07321332/ritonavir and also the combination of deferiprone with N-acetylcysteine for inhibiting the vicious circle of oxidative stress toxicity and endothelial cell damage. Most of these drugs are expected to be effective against all the SARS-CoV-2 variants including Omicron (B.1.1.529) and also the associated COVID-19 complications.
Keywords: Baricitinib; COVID-19; Drug targeting; Drugs; Health strategies; Molnupiravir; PF-07321332/ritonavir; SARS-CoV-2; Vaccines.
Publication
Journal: Medical Science Monitor
December/31/2021
Abstract
On 4th November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio®), received full regulatory approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Molnupiravir is an orally bioavailable antiviral drug for use at home when a SARS-CoV-2 test is positive. On 22nd December 2022, the FDA granted emergency use authorization (EUA) for the oral antiviral drug, nirmatrelvir/ritonavir (Paxlovid®) for adults and children with mild and moderate COVID-19 at increased risk of progression to severe COVID-19. These regulatory drug approvals come at a crucial time when new variants of concern of the SARS-CoV-2 virus are spreading rapidly. Although the FDA approved remdesivir (Veklury®) on 22nd October 2020 for use in adults and children for the treatment of COVID-19 requiring hospitalization, its use has been limited by the requirement for intravenous administration in a healthcare facility. The four FDA-approved therapeutic neutralizing monoclonal antibodies, imdevimab, bamlanivimab, etesevimab, and casirivimab are costly and also require medically-supervised intravenous administration. The availability of effective, low-cost oral antiviral drugs available in a community setting that can be used at an early stage of SARS-CoV-2 infection is now a priority in controlling COVID-19. An increasing number of repurposed antiviral drugs are currently under investigation or in the early stages of regulatory approval. This Editorial aims to present an update on the current status of orally bioavailable antiviral drug treatments for SARS-CoV-2 infection.
Publication
Journal: Medical Journal of the Islamic Republic of Iran
December/26/2021
Abstract
Background: The COVID-19 infection is a novel virus without any specific targeted therapies; thus, focusing on primary epidemiologic concerns, preventive strategies, risk factors, exacerbation factors, and mortality-related factors are of great importance to better control this disorder. There are some controversies about the factors associated with COVID-19 in different theories, and addiction is no exception. Methods: We conducted a large cross-sectional study of 513 hospitalized Iranian patients with COVID-19 infection to evaluate the severity of disease courses in patients with or without history of opium addiction. We recorded these data retrospectively after patients' discharge from the hospital. For the quantitative data, we used independent-samples t and Mann-Whitney tests. The qualitative data were calculated using Fisher exact and chi-square tests in IBM SPSS Statistics Version 22. Also, p<0.05 was considered statistically significant. Results: There was no significant difference regarding mean days of hospitalization in opium positive and negative groups (7.95±8.39 vs 8.35±5.11, respectively) (p=0.771); however, the need for intensive care unit (ICU) admission was significantly higher in the opium positive group (36% vs 11%) (p=0.005). The mean days of ICU stay was significantly higher in the opium positive group (2.36±3.81 vs 0.86±2.90) (p=0.026). The percentage of febrile patients, anosmia/hyposmia, and dysgeusia at the initiation of hospitalization was significantly lower in the opium positive group (39% vs 66%; 8% vs 23%; 8% vs; 20%, respectively) (p=0.002, 0.018, and.031, respectively). In the laboratory tests, only the white blood cell (WBC) count and the segmented cells were higher in the opium positive group (10.1±6.60 vs 7.38±4.14 and 73±20.47 vs 56.5±32.60, respectively) (p=0.018 and.001, respectively) and lymphocytes were lower in the opium positive (15.60±8.25 vs18.70±10.12) (p=0.048). Opium addicts had a significantly lower rate of azithromycin and lopinavir/ritonavir prescription in their initiation therapy (19% vs 34%, and 47% vs 70%, respectively) (p=0.038 and 0.012, respectively). Conclusion: Opium addict patients with COVID infection may be more febrile and experience more disease-specific symptoms and more severe disease course. These patients may show more evidence of laboratory inflammation and probable superinfections, so may manage with more caution and somehow different therapeutic regimen.
Keywords: Addiction; COVID-19; Corona; Drug Abuse; Opium; Outcome; SARS-CoV-2; Severity; Substance.
Publication
Journal: Frontiers in Bioscience - Elite
December/22/2021
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a lethal virus that was detected back on 31st December 2019 in Wuhan, Hubei province in China, and since then this virus has been spreading across the globe causing a global outbreak and has left the world fighting against the virus. The disease caused by the SARS-CoV-2 was named COVID-19 and this was declared a pandemic disease by the World Health Organization on 11th March 2020. Several nations are trying to develop a vaccine that can save millions of lives. This review outlines the morphological features of the virus describing the outer and inner structures of the virus along with the entry mechanism of the virus into the host body and the infection process. Detailed reports of global outbreak along with preventive measures have also been included, with special emphasis on China, the United States of America, India, Italy, and South Korea. Broad-spectrum antiviral drugs being used at various health care centres around the world, namely Remdesivir, Camostat & Nafamostat, Famotidine, Chloroquine & Hydroxychloroquine, Lopinavir/ritonavir, Ivermectin, and Tocilizumab & Sarilumab have also been included. World Health Organization guidelines on preventive measures and use of soaps, alcohol-based hand-rubs and wearing face masks have also been described. The vaccines that are in one of the phases of human trials, namely Oxford University's vaccine, the United States-based Moderna's vaccine, India's Covaxin and the Russian vaccine, have also been incorporated in the review article.
Keywords: COVID-19; Global outbreak; Morphology; Oxford’s vaccine; Remdesivir; SARS-CoV-2.
Publication
Journal: Journal of Environmental Pathology, Toxicology and Oncology
December/21/2021
Abstract
Over the years, a novel RNA coronavirus has emerged with mutational episodes. This virus was confirmed to cause severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus infectious disease-2019 (COVID-19). This particular emphasis has raised the risk signal at the global level. Hepatic injury has been known to be a major impairment with varying factors. In recent years, the mechanistic event of hepatic injury is now more controversial and has a lack of justifiable set. Nevertheless, it has been investigated for the prominence of inflammatory signals, viral load in hepatocytes, followed by an intensive care therapeutic defense, and/or drug toxicity. Limited reports are available on infection-mediated hepatic injury, and its associated mechanism is still poorly understood. In the context of COVID-19 infections, the initial episode is pulmonary disorder with a systemic infection in multiple organs, including the liver. The majority of the reported cases reveal hepatic damage or dysfunction among COVID-19-infected patients. Prevalence of altered biochemistry of liver enzymes was also observed in the COVID-19 infected population. Our review focuses on the probable mechanisms and therapeutic options of COVID-19 and its associated hepatic dysfunction. We also discuss the available prescribed medications against COVID-19 infections, such as remdesiver, oseltamivir, lopina-vir/ritonavir, ribavirin, anticoagulant, anti-inflammatory, and immune-based therapies.
Authors
Publication
Journal: Family Medicine
December/21/2021
Abstract
Objective: Covid19 has emerged as a greatest threat of the decade worldwide. At present there is no certain treatment for treating coronavirus diseases, while some antiviral drugs (Remdesivir , Lopinavir and Ritonavir) are under investigation. Many countries including India have adopted the convalescent plasma therapy in the treatment of moderate to severely ill patients. Despite the treatment being given ,there are no such evidences on the utility and efficacy of convalescent plasma. Hence this study tries to find out the impact on the discharge status from hospital of the patients receiving the very therapy.
Design: Systematic review and meta analysis.
Setting: An extensive search was made, following PRISMA guidelines on online databases such as Pubmed, Google scholar and Science direct. Studies those fulfilled the inclusion and exclusion criteria ,were included and reviewed and analyzed for a common outcome(discharge status).
Participants: A total of 6 eligible studies were analyzed qualitatively and quantitatively which included three case control, two case series and one case report.
Results: The overall pooled discharge rate from the above studies was 75.7% after the CP therapy. When analyzed for relative risk , it showed CP therapy having a lower risk of staying in hospital (not getting discharged) when compared to Standard therapy ,overall RR (relative risk) being 0.946.
Conclusion: Our study shows that there is always a higher rate of discharge and low risk of prolonged hospital stay in those patients who receive plasma therapy. CP therapy being a low cost and easy to administer therapy with very less adverse events, requires more focus on further research as it has a potential to become an ideal effective treatment option for COVID-19.
Keywords: COVID-19; Convalescent plasma; discharge status; plasma therapy.
Publication
Journal: Frontiers in Medicine
December/19/2021
Abstract
Introduction: Novel coronavirus (COVID-19) and tuberculosis (TB) are the newest and one of the oldest global threats, respectively. In the COVID-19 era, due to the health system's focus on the COVID-19 epidemic, the national TB control program received less attention, leading to a worsening of the global TB epidemic. In this study, we will review the characteristics of TB patients coinfected with COVID-19. Material and Methods: Using Scopus, PubMed/Medline, Embase, and Web of Science databases, a systematic search was performed. Case reports and case series on TB/COVID-19 coinfection published from January 1, 2019 to February 24, 2021 were collected. There were no limitations regarding publication language. Results: Eleven case series and 20 case reports were identified from 18 countries, with the majority them being from India (N = 6) and China (N = 4). Overall, 146 patients (114 men and 32 women) coinfected with TB and COVID-19 enrolled. Smoking (15.1%), diabetes (14.4%), and hypertension (8.9%) were the most frequent comorbidities among these patients. The COVID-19 patients with TB mainly suffered fever (78.8%), cough (63.7%), and respiratory distress (22.6%). Hydroxychloroquine (64.0%) and lopinavir/ritonavir (39.5%) were the most common treatments for them. The mortality rate was 13.0% and the rate of discharged patients was 87.0%. Conclusion: Global prevalence of COVID-19-related deaths is 6.6%. Our results showed that 13.0% of patients with TB/COVID-19 died. Thus, this study indicated that coinfection of TB and COVID-19 can increase the mortality. The respiratory symptoms of TB and COVID-19 are very similar, and this causes them to be misdiagnosed. In addition, TB is sometimes diagnosed later than COVID-19 and the severity of the disease worsens, especially in patients with underlying conditions. Therefore, patients with TB should be screened regularly in the COVID-19 era to prevent the spread of the TB/COVID-19 coinfection.
Keywords: COVID-19; TB; coinfection; review; tuberculosis.
Publication
Journal: Cannabis and Cannabinoid Research
December/16/2021
Abstract
Introduction: The year 2020 began with the world being flounced with a wave of novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) disease, named COVID-19. Based on promising pre-clinical and clinical data, remdesivir (RDV) was the first drug to receive FDA approval and so far, it is the most common therapy for treatment of SARS-CoV-2/MERS-CoV. However, following intravenous administration, RDV metabolizes majorly by human liver carboxylesterase 1 (CES1) and marginally by the CYP3A4 enzyme in merely less than an hour. Its resultant active metabolite is a hydrophilic nucleoside with very limited accumulation within lung tissues. Therefore, there is a need to investigate strategies to overcome such premature metabolism issues and improve the antiviral efficacy of RDV at the target site. Objective: Considering the major CES1-mediated metabolism of RDV on systemic administration, we intend to explore the remarkable CES1 plus CYP3A4 inhibitory activity of cannabidiol (CBD) against in vitro microsomal metabolism of RDV to indicate its therapeutic potential as an adjuvant to RDV in the treatment and management of COVID-19. Methods: We investigated the in vitro human liver microsomal metabolism of RDV in the presence of two potential CES1 inhibitors-CBD and nelfinavir, and two standard CYP3A4 inhibitors-ritonavir (RITO) and cyclosporin A. The microsomal metabolism assay was further validated by using a well-characterized CYP3A4-selective substrate, midazolam (MDZ), in the presence of CBD and RITO. Results: Our findings depicted that RDV was rapidly and completely metabolized by human liver microsomes within 60 min. Coincubation with CBD substantially reduced microsomal metabolism of RDV and prolonged its in vitro half-life from 8.93 to 31.07 min. CBD showed significantly higher inhibition of RDV compared with known CES1 and CYP3A4 inhibitors. Inhibition of MDZ metabolism by CBD and RITO further validated the assay. Conclusions: The current study strongly suggests that CBD significantly inhibits human liver microsomal metabolism of RDV and extends its in vitro half-life. Thus, concomitant administration of CBD with RDV intravenous injection could be a promising strategy to prevent premature metabolism in COVID-19 patients.
Keywords: COVID-19; CYP3A4 inhibitor; Remdesivir; cannabidiol; carboxylesterase 1 inhibitor; in vitro liver microsomal metabolism.
Publication
Journal: European Respiratory Review
December/15/2021
Abstract
Hospitalised patients with coronavirus disease 2019 (COVID-19) have a high mortality rate. There are an increasing number of published randomised controlled trials for anti-inflammatory, anti-viral and other treatments. The European Respiratory Society Living Guidelines for the Management of Hospitalised Adults with COVID-19 were published recently, providing recommendations on appropriate pharmacotherapy.Patient, Intervention, Comparator and Outcomes questions for key interventions were identified by an international panel and systematic reviews were conducted to identify randomised controlled trials meeting the inclusion criteria. The importance of end-points were rated, and mortality was identified as the key "critical" outcome for all interventions. Random-effects meta-analysis was used to pool studies and provide effect estimates for the impact of treatments on mortality.Corticosteroids, hydroxychloroquine, azithromycin, remdesivir, anti-interleukin (IL)-6 monoclonal antibodies, colchicine, lopinavir/ritonavir and interferon-β have been reviewed.Our results found further evidence in support of the use of corticosteroids, particularly dexamethasone, and anti-IL-6 receptor monoclonal antibody therapy. These data support the need to identify additional therapies with beneficial effects on mortality.
Publication
Journal: Arabian journal of chemistry
December/14/2021
Abstract
Background: COVID-19 is an ongoing viral pandemic produced by SARS-CoV-2. In light of in vitro efficacy, several medications were repurposed for its management. During clinical use, many of these medications produced inconsistent results or had varying limitations.
Objective: The purpose of this literature review is to explain the variable efficacy or limitations of Lopinavir/Ritonavir, Remdesivir, Hydroxychloroquine, and Favipiravir in clinical settings.
Method: A study of the literature on the pharmacodynamics (PD), pharmacokinetics (PK), safety profile, and clinical trials through academic databases using relevant search terms.
Results & discussion: The efficacy of an antiviral drug against COVID-19 is associated with its ability to achieve therapeutic concentration in the lung and intestinal tissues. This efficacy depends on the PK properties, particularly protein binding, volume of distribution, and half-life. The PK and PD of the model drugs need to be integrated to predict their limitations.
Conclusion: Current antiviral drugs have varying pharmacological constraints that may associate with limited efficacy, especially in severe COVID-19 patients, or safety concerns.
Keywords: Favipiravir; Hydroxychloroquine; Lopinavir; Pharmacodynamics; Pharmacokinetics; Remdesivir; SARS-CoV-2.
Publication
Journal: Arabian journal of chemistry
December/14/2021
Abstract
The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide (https://covid19.who.int/, 11 September 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CLpro). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide47-57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CLpro) to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future.
Keywords: 3CLpro main protease; COVID-19; In silico; Molecular docking; Repurposing drug; SARS-CoV-2; TAT-peptide.
Publication
Journal: Iranian Journal of Pharmaceutical Research
December/13/2021
Abstract
Coronavirus disease 2019 (COVID-19) management in patients with predisposing psychiatric disorders would be challenging due to potential drug-drug interactions (PDDIs) and precipitation of their disease severity. Furthermore, COVID-19 itself might precipitate or induce unpredicted psychiatry and neuropsychiatry complications in these patients. In this literature review study, the psychological impacts of COVID-19 and major psychiatric adverse drug reactions (ADRs) of COVID-19 treatment options have been discussed. A detailed Table has been provided to assess potential drug-drug interactions of COVID-19 treatment options with psychotropic medications to avoid unwanted major drug-drug interactions. Finally, potential mechanisms of these major drug-drug interactions and possible management of them have been summarized. The most common type of major PDDIs is pharmacokinetics. Hydroxychloroquine/chloroquine and lopinavir/ritonavir were the most involved anti-COVID-19 agents in these major PDDIs.
Keywords: Adverse drug reactions; COVID-19; Drug-drug interactions; Pharmacokinetics; Psychotropic medication.
Publication
Journal: Frontiers in Pharmacology
December/12/2021
Abstract
The global epidemic outbreak of the coronavirus disease 2019 (COVID-19), which exhibits high infectivity, resulted in thousands of deaths due to the lack of specific drugs. Certain traditional Chinese medicines (TCMs), such as Xiyanping injection (XYPI), have exhibited remarkable benefits against COVID-19. Although TCM combined with Western medicine is considered an effective approach for the treatment of COVID-19, the combination may result in potential herb-drug interactions in the clinical setting. The present study aims to verify the effect of XYPI on the oral pharmacokinetics of lopinavir (LPV)/ritonavir (RTV) using an in vivo rat model and in vitro incubation model of human liver microsomes. After being pretreated with an intravenous dose of XYPI (52.5 mg/kg) for one day and for seven consecutive days, the rats received an oral dose of LPV/RTV (42:10.5 mg/kg). Except for the t1/2 of LPV is significantly prolonged from 4.66 to 7.18 h (p < 0.05) after seven consecutive days pretreatment, the pretreatment resulted in only a slight change in the other pharmacokinetic parameters of LPV. However, the pharmacokinetic parameters of RTV were significantly changed after pretreatment with XYPI, particularly in treatment for seven consecutive days, the AUC0-∞ of RTV was significantly shifted from 0.69 to 2.72 h μg/mL (p < 0.05) and the CL exhibited a tendency to decrease from 2.71 L/h to 0.94 L/h (p < 0.05), and the t1/2 of RTV prolonged from 3.70 to 5.51 h (p < 0.05), in comparison with the corresponding parameters in untreated rats. After administration of XYPI, the expression of Cyp3a1 protein was no significant changed in rats. The in vitro incubation study showed XYPI noncompetitively inhibited human CYP3A4 with an apparent Ki value of 0.54 mg/ml in a time-dependent manner. Our study demonstrated that XYPI affects the pharmacokinetics of LPV/RTV by inhibiting CYP3A4 activity. On the basis of this data, patients and clinicians can take precautions to avoid potential drug-interaction risks in COVID-19 treatment.
Keywords: CYP3A4; coronavirus disease 2019; herb-drug interactions; lopinavir/ritonavir; xiyanping injection.
Publication
Journal: Frontiers in Medicine
December/12/2021
Abstract
Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, China in December 2019. At present, COVID-19 has emerged as a global pandemic. The clinical features of this disease are not fully understood, especially the interaction of COVID-19 and preexisting comorbidities and how these together further impair the immune system. In this case study, we report a COVID-19 patient with cirrhosis. A 73-year-old woman with cirrhosis reported a fever and cough on February 6, 2020. CT of the chest indicated an infection in her bilateral lungs. She tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The woman was treated with lopinavir and ritonavir tablets and interferon alpha-2b injection, but there was no obvious effect. Although this patient was basically asymptomatic after 2 days in the hospital, the inflammation of the bilateral lungs was slow to subside as shown in CT of the chest. In addition, the white blood cell count (WBC), absolute neutrophil count, and absolute lymphocyte count remained decreased and the result of real-time reverse transcription polymerase chain reaction (PCR) (rRT-PCR) assay was still positive for SARS-CoV-2 on hospital day 28. After infusion of plasma from a recovered COVID-19 patient four times, the patient tested negative for SARS-CoV-2. She was discharged on March 13, 2020. This patient tested negative for SARS-CoV-2 after infusion of plasma from a recovered COVID-19 patient four times. Cirrhosis could impair the homeostatic role of the liver in the systemic immune response, which may affect the removal of SARS-CoV-2. This could lead to a diminished therapeutic effect of COVID-19. Thus, clinicians should pay more attention to COVID-19 patients with cirrhosis.
Keywords: COVID-19; SARS-CoV-2; cirrhosis; cured patient; treatment.
Publication
Journal: Revista Espanola de Quimioterapia
December/10/2021
Abstract
The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.
Keywords: AZD7442; Adalimumab; Anakinra; Azithromycin; BRII-196; BRII-198; Banlanivimab; Baricitinib; COVID-19; Canakinumab; Casirivimab; Certolizumab; Ciganilmab; Colchicine; Dexamethasone; Etanercept; Etesevimab; Evusheld; Favipiravir; Fluvoxamine; Golimumab; Hydroxychloroquine; Imdevinab; Infliximab; Itolizumab; Ivermectin; Lemilumab; Lopinavir/Ritonavir; Metformin; Molnupiravir; PF-07321332; Paxlovid; Ravulizumab; Remdesivir; Ruxolitinib; SARS-CoV-2; Sarilumab; Sotrovimab; Tixagevimab; Tocilizumab; Tofacitinib; Vitamin D; convalescent plasma; treatment.
Publication
Journal: Journal of Biomolecular Structure and Dynamics
December/7/2021
Abstract
COVID-19 is a worldwide health crisis seriously endangering the arsenal of antiviral and antibiotic drugs. It is urgent to find an effective antiviral drug against pandemic caused by the severe acute respiratory syndrome (Sars-Cov-2), which increases global health concerns. As it can be expensive and time-consuming to develop specific antiviral drugs, reuse of FDA-approved drugs that provide an opportunity to rapidly distribute effective therapeutics can allow to provide treatments with known preclinical, pharmacokinetic, pharmacodynamic and toxicity profiles that can quickly enter in clinical trials. In this study, using the structural information of molecules and proteins, a list of repurposed drug candidates was prepared again with the graph neural network-based GEFA model. The data set from the public databases DrugBank and PubChem were used for analysis. Using the Tanimoto/jaccard similarity analysis, a list of similar drugs was prepared by comparing the drugs used in the treatment of COVID-19 with the drugs used in the treatment of other diseases. The resultant drugs were compared with the drugs used in lung cancer and repurposed drugs were obtained again by calculating the binding strength between a drug and a target. The kinase inhibitors (erlotinib, lapatinib, vandetanib, pazopanib, cediranib, dasatinib, linifanib and tozasertib) obtained from the study can be used as an alternative for the treatment of COVID-19, as a combination of blocking agents (gefitinib, osimertinib, fedratinib, baricitinib, imatinib, sunitinib and ponatinib) such as ABL2, ABL1, EGFR, AAK1, FLT3 and JAK1, or antiviral therapies (ribavirin, ritonavir-lopinavir and remdesivir).Communicated by Ramaswamy H. Sarma.
Keywords: COVID-19; Drug similarity; drug affinity; drug repurposing; graph neural network; kinase inhibitors.
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