ABSTRACT
In novel coronavirus disease 2019 (COVID-19), liver injury was found at a high rate, and reports from outside Japan revealed that such injury was related to severity. We examined the characteristics of liver injury in 15 cases of COVID-19. Thirteen of these patients received antiviral therapy, such as favipiravir, remdesivir, and hydroxychloroquine. Liver injury was observed in eight cases at admission for COVID-19. The hepatic CT attenuation values at admission were significantly lower in nine patients who developed liver damage or showed its exacerbation during the treatment than in the remaining patients. Drug-induced liver injury due to antiviral drug was suspected in six cases. Liver injury due to COVID-19 may be related to low hepatic CT attenuation values and be modified by antiviral drugs.Copyright © 2021 The Japan Society of Hepatology.
ABSTRACT
Timely, effective, and safe antiviral therapy in COVID-19 patients reduces complications, disability and mortality rates. The greatest concern with remdesivir is the risk of drug-induced liver injury, including in patients whose liver function is compromised by COVID-19. The aim of the study was to investigate the efficacy and safety of remdesivir in patients with confirmed SARSCoV-2 infection who had been admitted to an infectious diseases hospital in the Volgograd region in March 2022. Material(s) and Method(s): the authors carried out an open, non-randomised, single-arm study using medical records of 234 patients who had been diagnosed with "U07.1 COVID-19, virus identified" and prescribed remdesivir upon admission. The effectiveness of therapy was evaluated using two criteria: the need for oxygen supplementation or ventilatory support, or mortality. The authors conducted the evaluation on days 7, 14, and 28 using the six-point ordinal severity scale by Y. Wang et al. The safety of therapy was assessed on the basis of complaints and changes in laboratory findings. Result(s): for the patients prescribed remdesivir at admission, the 7-day mortality rate was 3.0%, the 14-day mortality rate was 5.6%, and the 28-day mortality rate was 7.3%. With the exception of a patient with myocardial infarction, all the patients who had been hospitalised with mild COVID-19 and prescribed remdesivir did not require oxygen therapy and/or transfer to intensive care and were discharged following recovery. The patients with moderate to severe COVID-19 had the 14-day mortality rate of 6.4% and the 28-day mortality rate of 8.6%. 17 patients (7.2%) discontinued remdesivir prematurely for various reasons, including adverse drug reactions. Remdesivir therapy of 5-10 days was associated with an increase in ALT activity by 2.7 +/- 0.8 times in 15.9% of patients with mild COVID-19, by 3.8 +/- 1.8 times in 20.4% of patients with moderately severe COVID-19, and by 4.8 +/- 2.7 times in 24% (12/50) of patients with severe COVID-19. In two patients (0.9%), the increase exceeded 10-fold the upper limit of normal. Conclusion(s): the obtained results support recommending remdesivir to patients with mild, moderate and severe COVID-19, including those with moderately elevated baseline activity of hepatic transaminases.Copyright © NEICON ISP LLC. All rights reserved.
ABSTRACT
Remdesivir (GS-5734) is a new direct-acting antiviral drug in the nucleotide analogue class with antiviral activity against SARS-CoV-2 and the ability to inhibit RNA-dependent RNA polymerase. Preliminary results from phase III randomized clinical trials of remdesivir are inconsistent. Understanding the fact of the limited world experience with the use of remdesivir in COVID-19 required further study of its efficacy and safety in real clinical practice. The aim of the study is to evaluate the efficacy and safety of remdesivir in the treatment of patients with COVID-19. Material and methods. The study included 1422 patients with a novel coronavirus infection (COVID-19) who received remdesivir as part of complex therapy in a hospital setting at medical organizations of the Moscow public health system. Additionally, standard therapy was carried out, regulated by the Interim Guidelines "Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19)" of the Ministry of Healthcare of the Russian Federation, the current version. The efficacy of the drug was assessed based on primary and secondary efficacy points. Primary variable: 1) cumulative incidence of clinical outcomes in patients with COVID-19 treated with remdesivir as part of complex therapy;2) median time to clinical improvement according to the World Health Organization ordinal categorical scale (under clinical improvement, the patient is assumed to move >2 categories towards improvement in clinical condition). Secondary variables: 1) median time to achieve <2 NEWS scores lasting at least 24 hours or hospital discharge;2) mortality from all causes;3) duration of fever (>38 degreeC), days;4) duration of hospitalization, days;5) time to achieve elimination of the pathogen from the upper respiratory tract (no SARS-CoV-2 RNA), days. The safety of remdesivir was assessed based on the registration of adverse events using the method of spontaneous reports. Results. The analysis of clinical outcomes of treatment showed that 1195 (84.1%) patients recovered, death from all causes occurred in 227 (15.9%) patients. The median improvement in clinical status on the World Health Organization ordinal categorical scale was 6 days. The median time to reach a NEWS score of <2, lasting at least 24 hours, or hospital discharge was 4 days. The median duration of fever was 3 days from the start of remdesivir administration. The median length of hospital stays for patients included in the Register was 9 days. Adverse reactions associated with the use of remdesivir were recorded in 11 (0.7%) patients. Serious adverse reactions were not registered. During hospitalization, all adverse reactions were resolved. Conclusion. A retrospective analysis of data from the Registry of 1422 patients with COVID-19 who received remdesivir as part of complex therapy in medical organizations of the state healthcare system of Moscow in routine clinical practice showed clinical efficacy and a favorable safety profile of remdesivir (Remdeform, lyophilizate for solution for intravenous administration 100 mg, manufactured by JSC Pharmasyntez, Russia). The data obtained are consistent with previous randomized clinical trials of remdesivir and allow us to recommend its further use in patients with COVID-19 as part of complex therapy.Copyright © The Author(s), 2022.
ABSTRACT
Background: Currently, the present world is facing a new deadly challenge from a pandemic disease called COVID-19, which is caused by a coronavirus named SARS-CoV-2. To date, no drug or vaccine can treat COVID-19 completely, but some drugs have been used primarily, and they are in different stages of clinical trials. This review article discussed and compared those drugs which are running ahead in COVID-19 treatments. Method(s): We have explored PUBMED, SCOPUS, WEB OF SCIENCE, as well as press releases of WHO, NIH and FDA for articles related to COVID-19 and reviewed them. Result(s): Drugs like favipiravir, remdesivir, lopinavir/ritonavir, hydroxychloroquine, azithromycin, ivermectin, corticosteroids and interferons have been found effective to some extent, and partially approved by FDA and WHO to treat COVID-19 at different levels. However, some of these drugs have been disapproved later, although clinical trials are going on. In parallel, plasma therapy has been found fruitful to some extent too, and a number of vaccine trials are going on. Conclusion(s): This review article discussed the epidemiologic and mechanistic characteristics of SARS-CoV-2, and how drugs could act on this virus with the comparative discussion on progress and drawbacks of major drugs used till date, which might be beneficial for choosing therapies against COVID-19 in different countries.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
Liver enzyme abnormalities occur frequently in patients diagnosed with Coronavirus disease 2019 (COVID-19). It has been suggested that patients with severe acute liver injury are more likely to be admitted to intensive care, require intubation or renal replacement therapy and their mortality rate is higher than patients without severe acute liver injury. This review article explores the possible aetiologies of liver dysfunction seen in patients with COVID-19 and also the effect of COVID-19 on patients with pre-existing liver disease. Finally, we suggest clinical approaches to treating a patient with liver enzyme disturbance and COVID-19 and also caring for patients who require liver transplantation in the COVID-19 era.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
Antiviral therapy is important for COVID-19. Currently, the anti-2019-nCoV drugs in clinical trials include broad-spectrum antiviral drugs (alpha interferon and ribavirin), hemagglutinin inhibitors (arbidol), human immunodeficiency virus protease inhibitors (lopinavir/ritonavir and darunavir/cobicistat), nucleoside analogues (favipiravir and remdesivir) and antimalarial drug (chloroquine);while liver damage may occur in some patients with the medication. This article reviews the research on liver damage associated with anti-2019-nCoV drugs, aiming at promoting the safe and effective antiviral therapy for COVID-19 patients.Copyright © 2020 by the Chinese Medical Association.
ABSTRACT
The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19. Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes. Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine. Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.Copyright © Team of Authors, 2022.