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1.
Maturitas ; 173:97, 2023.
Article in English | EMBASE | ID: covidwho-20245353

ABSTRACT

Objective: The current study aimed to describe the clinical characteristics of mild SARS-CoV-2 infected pregnant women with abnormal liver function (ALF), explore the association between ALF with maternal and fetal outcomes. Method(s): This retrospective analysis included 87 pregnant patients with mild SARS-CoV-2 infection admitted and treated from December 1, 2022, to 31, 2022 in the department of Obestircs at Beijing Obstetrics and Gynecology Hospital. We evaluated patients for demographic and clinical features, laboratory parameters and pregnancy complications. Result(s): 27 Patients in this cohort had clinical presentations of ALF. Compared with the control group, the peripheral blood platelet (PLT), D-dimer quantitative determination (D-Dimer), lactate dehydrogenase (LDH), total protein (TP), albumin (ALB), indirect bilirubin (DBIL), gamma- glutamyltranspeptidase (GGT) and total bile acid (TBA) showed significantly differences (p<0.05). 12 cases (44.44%) complicated with pregnancy induced hypertension (PIH), 14 cases (51.85%) complicated with intrahepatic cholestasis of pregnancy (ICP), 2 cases (7.4%) complicated with acute fatty liver during pregnancy (AFLP) and 5 cases (14.81%) complicated with postpartum hemorrhage in patients with abnormal LFT were significantly higher than those in the control group (p<0.05). Compared with the control group, the incidence of premature delivery (22.22%) and fetal distress (37.04%) in the experiment group were significantly higher (p<0.05), and the incidence of neonatal asphyxia was not significantly different (p>0.05). Conclusion(s): Pregnant women are generally susceptible to mild SARS-CoV-2 and may induce ALF. ALF is associated with increased risk of mother and infant. The maternal and infant outcomes of those who terminated pregnancy in time are acceptable. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating liver function and relevant indicators. The long-term outcomes in the future are worth to further study.Copyright © 2023

2.
Kanzo/Acta Hepatologica Japonica ; 62(6):381-383, 2021.
Article in Japanese | EMBASE | ID: covidwho-20244958

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.

3.
British Journal of Haematology ; 201(Supplement 1):167, 2023.
Article in English | EMBASE | ID: covidwho-20238486

ABSTRACT

Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.

4.
Revue Medicale Suisse ; 16(691):863-868, 2020.
Article in French | EMBASE | ID: covidwho-20238148

ABSTRACT

The SARS-coronavirus 2 disease initially reported in December 2019 in China (COVID-19) represents a major challenge for intensive care medicine, due to the high number of ICU admission and the prolonged stay for many patients. Up to 5% of COVID-19 infected patients develop severe acute hypoxemic respiratory failure requiring invasive mechanical ventilation as supportive treatment. Apart from early antiviral and anti-inflammatory treatment, the management of COVID-19 patients is mainly applying protective mechanical ventilation, to support the injured lungs. However recently acquired data and clinical experience suggest that COVID-19-related ARDS presents some specificities that will be summarized in the present article.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

5.
Ankara Universitesi Eczacilik Fakultesi Dergisi ; 46(2):505-522, 2022.
Article in Turkish | EMBASE | ID: covidwho-20238118

ABSTRACT

Objective: Viruses are agents that can infect all kinds of living organisms, and the most important hosts are humans, animals, plants, bacteria and fungi. Viral diseases are responsible for serious morbidity and mortality worldwide, are a major threat to public health, and remain a major problem worldwide. The recently prominent Coronaviruses (CoVs) within this group belong to the Coronaviridae family, subfamily Coronavirinae, and are large (genome size 26-32 kb), enveloped, single-stranded ribonucleic acid (RNA ) viruses that can infect both animals and humans. The world has experienced three epidemics caused by betaCoVs in the last two decades: SARS in 2002-03, MERS in 2012, and COVID-19, first identified in 2019. COVID-19 continues to be our current health problem and studies on the subject continue. Result and Discussion: The term "antiviral agents" is defined in very broad terms as substances other than virus-containing vaccine or specific antibody that can produce a protective or therapeutic effect for the clearly detectable effect of the infected host. Nature has the potential to cure humanity's helplessness against viruses with many different plant species with strong antiviral effects. During the screening of plants with antiviral effects, focusing on plants used in folk medicine is of great importance in terms of maximizing the benefit to humanity - saving time and effort by dealing with valuable ancient knowledge on a scientific basis. In this review, viral diseases and the plants used in these diseases and determined to be effective are mentioned.Copyright © 2022 University of Ankara. All rights reserved.

6.
Prescriber ; 34(4):23-26, 2023.
Article in English | EMBASE | ID: covidwho-20236237

ABSTRACT

Respiratory syncytial virus (RSV) infection remains a major public health problem, especially in younger children and the elderly. But several monoclonal antibodies, antivirals and vaccines, either recently launched or in development, offer new hope for RSV prevention and treatment.Copyright © 2023 Wiley Interface Ltd.

7.
Acta Haematologica Polonica ; 54(2):82-85, 2023.
Article in English | EMBASE | ID: covidwho-20235121

ABSTRACT

Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.

8.
Health Biotechnology and Biopharma ; 6(4):43-55, 2023.
Article in English | EMBASE | ID: covidwho-20233997

ABSTRACT

Worldwide, infectious diseases have contributed significantly to morbidity and mortality;among the leading causes of death are pneumonia, respiratory infections and Covid-19. Stem cell therapy will be used to treat virus-infected patients in an effective and safe manner. A cross-sectional questionnaire was used to collect data from doctors. Most doctors are aware of the applications of stem cells, but they do not confirm their usage because clinical trials are ongoing. Instead, they show support for using stem cells to treat patients. Stem cells have been hoping to help repair damaged tissues in the respiratory system to promote faster recovery. Stem Cells are being studied in current clinical trials for their efficacy and safety in virus severe pneumonia and respiratory infections. The doctors suggested that stem cells have been used in infectious diseases to improve their health.Copyright © 2023 Health Biotechnology And Biopharma. All rights reserved.

9.
Value in Health ; 26(6 Supplement):S102-S103, 2023.
Article in English | EMBASE | ID: covidwho-20233924

ABSTRACT

Objectives: Efforts to combat COVID-19 have largely focused on vaccination and non-pharmaceutical interventions to decrease hospitalization and death and to reduce transmission. First generation COVID-19 direct-acting antivirals (DAAs) are only authorized for high-risk patients to reduce individual risk of disease progression. However, DAAs can also impact transmission by reducing viral load, thereby shortening the duration of infectivity. Next generation oral DAAs in development may have safety profiles that are amenable to broader eligibility and use. This analysis estimates the economic and clinical impact of increasing the utilization of DAAs to treat COVID-19. Method(s): A susceptible-infected-recovered-susceptible model was developed to estimate COVID-19-related outcomes based on DAA uptake. Cost-savings modeled included reduced healthcare utilization amongst individual patients and, importantly, potential savings attributable to reduced transmission. Cost inputs included treatment acquisition costs, adverse events, healthcare utilization, and productivity losses based on published literature. One million individuals were assessed with clinical and economic outcomes estimated for DAA adoption by risk level. Result(s): The model projects 402,330 new infections per 1 million individuals annually, leading to 6,000 hospitalizations and 107 deaths. By increasing DAA use by 10% in the high-risk population and 20% in the standard-risk population, infections decreased to 312,000, with 1,800 fewer hospitalizations and 34 fewer deaths. Decreases in medical encounters were driven by reduction in transmission (77% of the decrease) and reduction in severity amongst those treated (23% of the decrease). Among deaths averted, 72% were attributable to the reduction in transmission. Overall, costs decrease by 23.5% with increased treatment. Conclusion(s): This study is among the first to model the potential population-level impact of DAAs in reducing infectivity and transmission, a factor currently under-emphasized in the literature. New DAAs under development with potentially improved safety profiles may expand the uptake of treatment and substantially reduce the clinical and economic burden of COVID-19.Copyright © 2023

10.
Value in Health ; 26(6 Supplement):S39, 2023.
Article in English | EMBASE | ID: covidwho-20233799

ABSTRACT

Objectives: Development of new and repurposed medicines in response to the COVID-19 pandemic has occurred at an unprecedented rate, resulting in a dynamic pipeline marked by significant challenges and successes. This analysis provides an overview of the vaccines and therapies undergoing clinical evaluation or with recent approval for the treatment and prevention of COVID-19 in global markets. Method(s): For this analysis, COVID-19 pipeline medicines are defined in three categories: vaccines, new treatments and repurposed medicines. GlobalData is the primary data source for this study, in addition to online databases from Health Canada, the US FDA, and the EMA. International markets examined include the US and geographic Europe (excluding Russia and Turkey). Result(s): As of November 2022, the global pipeline contained over 600 therapies and vaccines undergoing Phase I, II, III clinical trials or pre-registration for the prevention and treatment of COVID-19. Preventive and repurposed medicines include antivirals, immunoglobulins, monoclonal antibodies, cellular therapies, and convalescent plasma. In Canada, twelve medicines, including six vaccines, have been approved for COVID-19. The number of global approvals is greater, with approximately 9 vaccines on the market in OECD countries. In addition to pre-exposure preventative therapies, manufacturers are also developing COVID-19 drugs to be used as prophylactic therapy. The analysis identifies new oral antiviral treatments and preventative therapies in the pipeline and under review in various jurisdictions globally. Conclusion(s): This research provides a clearer picture of the characteristics and evolution of the market for new and emerging COVID-19 medicines, which will help policy-makers and other stakeholders understand and anticipate the unique pressures of the COVID-19 pandemic.Copyright © 2023

11.
Value in Health ; 26(6 Supplement):S33, 2023.
Article in English | EMBASE | ID: covidwho-20233097

ABSTRACT

Objectives: To describe and compare real-world outcomes for patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19, treated with sotrovimab versus untreated. Method(s): Electronic health records from the National COVID Cohort Collaborative were used to identify US patients (aged >=12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (26 May 2021-30 April 2022) who met Emergency Use Authorization high-risk criteria. Patients receiving the monoclonal antibody (mAb) sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort with an index date on the day of infusion. Untreated patients (no evidence of early mAb treatment or prophylaxis mAb or oral antiviral treatment) were assigned to the untreated cohort with an imputed index date based on the time distribution between diagnosis and sotrovimab infusion for the sotrovimab cohort. The primary endpoint was hospitalization or death (both all-cause) within 29 days of index, reported as descriptive rates and adjusted (via inverse-probability-of-treatment weighting [IPTW]) odds ratios (OR) and 95% confidence intervals (CI). Result(s): Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis time period, 4,992 met the criteria for the sotrovimab cohort and 541,325 were included in the untreated cohort. Patients in the sotrovimab cohort were older (60 versus 54 years), more likely to be male (40% versus 38%) and White (85% versus 75%), and met more EUA criteria (3 versus 2) versus the untreated cohort. The 29-day hospitalization or mortality rates were 3.5% (176/4,992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts respectively (unadjusted OR [95% CI]: 0.77 [0.67,0.90];p=0.001;IPTW-adjusted OR [95% CI]: 0.74 [0.61,0.91];p=0.004). Conclusion(s): Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalization, mortality) between 26 May 2021-30 April 2022, which included the Delta variant and early surge of Omicron BA.1/BA.2. Funding(s): GSK (Study 219020)Copyright © 2023

12.
Infectious Microbes and Diseases ; 4(3):85-93, 2022.
Article in English | EMBASE | ID: covidwho-20232428
13.
Geroscience ; 2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-20241606

ABSTRACT

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic viruses of the genus Henipavirus, family Paramyxoviridae that cause severe disease outbreaks in humans and also can infect and cause lethal disease across a broad range of mammalian species. Another related Henipavirus has been very recently identified in China in febrile patients with pneumonia, the Langya virus (LayV) of probable animal origin in shrews. NiV and HeV were first identified as the causative agents of severe respiratory and encephalitic disease in the 1990s across Australia and Southern Asia with mortality rates reaching up to 90%. They are responsible for rare and sporadic outbreaks with no approved treatment modalities. NiV and HeV have wide cellular tropism that contributes to their high pathogenicity. From their natural hosts bats, different scenarios propitiate their spillover to pigs, horses, and humans. Henipavirus-associated respiratory disease arises from vasculitis and respiratory epithelial cell infection while the neuropathogenesis of Henipavirus infection is still not completely understood but appears to arise from dual mechanisms of vascular disease and direct parenchymal brain infection. This brief review offers an overview of direct and indirect mechanisms of HeV and NiV pathogenicity and their interaction with the human immune system, as well as the main viral strategies to subvert such responses.

14.
Viruses ; 15(5)2023 05 17.
Article in English | MEDLINE | ID: covidwho-20237711

ABSTRACT

OBJECTIVE: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. METHODS: We conducted a retrospective analysis on 2606 outpatient individuals with mild to moderate COVID-19 at risk for disease progression, hospitalization, or death. After receiving either SOT (420/2606), MOL (1788/2606), or N/R (398/2606), patients were followed-up with regarding primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. RESULT: A total of 2606 patients were treated at the outpatient clinic (SOT: 420; N/R: 398; MOL: 1788). 3.2% of the SOT patients (1 ICU admission), 0.8% of the MOL patients (2 ICU admissions), and none of the N/R patients were hospitalized. 14.3% of the N/R patients reported strong to severe side effects, exceeding SOT (2.6%) and MOL (5%) patients. A reduction in COVID symptoms after the treatment was experienced by 43% of patients in both the SOT and MOL groups and by 67% of patients in the N/R group, respectively. Women had a higher chance of symptom improvement with MOL (OR 1.2, 95%CI 1.0-1.5). CONCLUSION: All antiviral treatment options effectively prevented hospitalization in high-risk COVID-19 patients and were well tolerated. Side effects were pronounced in patients with N/R.


Subject(s)
COVID-19 , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Outpatients , Retrospective Studies , Antiviral Agents/adverse effects , Disease Progression , Lactams , Leucine
15.
Children (Basel) ; 10(5)2023 Apr 29.
Article in English | MEDLINE | ID: covidwho-20237513

ABSTRACT

In children, coronavirus disease 2019 (COVID-19) starts as a minor illness compared to adults, but during the ongoing COVID-19 pandemic, distinct SARS-CoV-2 variants and subvariants have changed options for therapies in both adults and children, especially for those with comorbidities such as allergies. On 25 April 2022, Remdesivir (RDV), a viral RNA-dependent RNA polymerase inhibitor, was approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 28 days and older, weighing ≥3 kg, hospitalized or non-hospitalized, who are at high risk of progression to severe forms of COVID-19. While RDV has been shown to have favorable effects in numerous types of research conducted on adults, such as shortening hospital stays, and has shown it has antiviral effects on various RNA viruses, there is a lack of findings regarding safety, tolerability, and efficacy of RDV in allergic pediatric patients since its initial FDA approval. This study aims to assess RDV's efficacy and tolerability in treating pediatric patients with mild and severe forms of COVID-19-associated allergies such as asthma, allergic rhinitis, and atopic dermatitis and how RDV affects the duration of hospitalization, especially for these comorbidities. The most recent pandemic wave among children rose due to the high transmissibility of the Omicron variant, and this study analyzed changes between July 2020 and September 2022 at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș", Bucharest, Romania. Our retrospective study included 250 children <18 years old, 42 (16.8%) had allergies, 132 were males (52.8%), age group 0-5 years old (80%), with a positive viral test for SARS-CoV-2. Severity was categorized as mild (43.6%), moderate (53.2%), and severe (1.6%) COVID-19, and treatment with RDV was administered in 50.4% (126/250) of children included in the study. The presence of comorbidities, asthma (7.2%), allergic rhinitis (4.4%), and atopic dermatitis (4.4%), was associated with an increased risk of developing severe COVID-19 infection in children, p < 0.05. We did not register deaths and severe complications; all cases evolved favorably under the instituted treatment. Laboratory abnormalities in transaminase levels 53.97% (ALT) and 61.9% (AST) were grades 1 or 2 and did not require discontinuation of the antiviral treatment, p < 0.05. RDV in children reduced the duration and evolution of COVID-19 and decreased the length of hospitalization in group-associated allergies; p < 0.05. This article summarizes RDV's efficacy among children with COVID-19 and allergies when the clinical result was improved and reports positive effects on tolerability and reduced duration of hospitalization, especially in children with asthma, atopic dermatitis, and allergic rhinitis. More studies are needed to confirm our findings.

16.
Int J Mol Sci ; 24(10)2023 May 16.
Article in English | MEDLINE | ID: covidwho-20236306

ABSTRACT

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Pandemics/prevention & control , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Interferons/therapeutic use
17.
Cureus ; 15(6): e40148, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-20234757

ABSTRACT

During the COVID-19 pandemic, variants of the Betacoronavirus SARS-CoV-2, the etiologic agent of COVID-19 disease, progressively decreased in pathogenicity up to the Omicron strain. However, the case fatality rate has increased from Omicron through each major Omicron subvariant (BA.2/BA.4, BA.5, XBB.1.5) in the United States of America. World data also mirror this trend. We show that the rise of Omicron pathogenicity is exponential, and we have modeled the case fatality rate of the next major subvariant as 0.0413, 2.5 times that of the Alpha strain and 60% of the original Wuhan strain which caused the greatest morbidity and mortality during the pandemic. Small-molecule therapeutics have been developed, and some of these, such as chlorpheniramine maleate, may be useful in the event of an Omicron subvariant of higher risk.

18.
United European Gastroenterol J ; 11(5): 431-447, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-20230969

ABSTRACT

BACKGROUND: Immunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs. OBJECTIVE: This study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan-coronavirus infection in cell and human airway organoids (hAOs) culture models. METHODS: Different coronaviruses (including wild type, delta and omicron variants of SARS-CoV-2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested. RESULTS: Dexamethasone and 5-aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6-thioguanine (6-TG), tofacitinib and filgotinib treatment dose-dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS-CoV-2 was 0.62 µM and the half maximum cytotoxic concentration (CC50) was above 30 µM, which resulted in a selective index (SI) of about 50. The anti-coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6-TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity. CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use
19.
Hepatology International ; 17(Supplement 1):S19-S20, 2023.
Article in English | EMBASE | ID: covidwho-2322379

ABSTRACT

In 1990, the seroprevalence of antibody against hepatitis C virus (anti- HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been well-documented by REVEL-HCV study. A national program of antiviral therapy for chronic viral hepatitis was launched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups. When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO's 2030 goals in 2025. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019. There are triple focuses of hepatitis C elimination in Taiwan including (1) therapy spearheads prevention, (2) screening supports therapy, and (3) prevention secures outcome. A total of US$1.7 billion will be allocated from 2017 to 2025 for the elimination of HCV. The coverage of HCV screening and treatment has been increasing significantly since 2017. The HCV screening coverage was almost 100% for dialytic patients, 96% for HIV-infected patients, 65% for patients under opioid substitution treatment, 63% for patients in the pre-end-stage renal disease care program, 57% for patients in the early chronic kidney disease care program, 52% for patients in diabetes care program, 39% for prisoners, and 38% for adults aged 45-79 years old in the general population by April 30, 2020. The budget to cover the cost of DAA increased from US$101 million in 2017 to US$219 million in 2019. The number of chronic hepatitis C patients receiving DAA therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,806 in 2019. However, the number of DAA-treated CHC patients reduced to 36,159 in 2020 and 20,559 in 2021 due to the COVID-19 pandemic. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, over 98.6% after 2019. It is expected that Taiwan will achieve WHO's HCV elimination goal by 2025.

20.
International Journal of Infectious Diseases ; 130(Supplement 2):S89, 2023.
Article in English | EMBASE | ID: covidwho-2322242

ABSTRACT

Intro: Oral antiviral agents with differing modes of action are now available for the treatment of COVID-19. However, potentially life-threatening drug-drug interactions (DDIs) may occur if patients' underlying co-morbidities are treated with medications that are contraindicated with ritonavir-containing antivirals. This study evaluated the prevalence and severity of potential DDIs (pDDIs) with ritonavir-containing COVID-19 oral antiviral therapy among the Australian population. Method(s): Adult patients supplied with >=1 medication between January 1, 2019, and December 31, 2019, were identified in the PBS10 dataset, a longitudinal, random 10% sample of the national Pharmaceutical Benefits Scheme (PBS) data for supplied prescriptions. Patients receiving medications that have pDDIs with a ritonavir-containing COVID-19 antiviral treatment were classified as the pDDI group, using data sources from University of Liverpool, Lexicomp, or the US Food and Drugs Administration. Finding(s): Over 1,434,000 patients in the PBS10 were supplied with >=1 medication during the study period. The majority (58.8%) had been prescribed at least one medication with pDDI with ritonavir-containing treatment. Among all patients with pDDIs, 43.3% of them were major or contraindicated, followed by moderate (15.1%), and minor pDDIs (1.9%). Patients with cancer had the highest prevalence of contraindicated or major pDDIs (79.5%), followed by dementia and/or Alzheimer's (77.2%), and diabetes (73.8%). Elderly patients (>=60 years old) also had a higher prevalence of contradicted or major pDDI (65.4%) than the general patient population. Conclusion(s): Our results demonstrated that one-third of the Australian adult population in the PBS10 dataset may be classified as contraindicated with ritonavir-containing COVID-19 therapies. The prevalence of pDDI is much higher in elderly patients and in patients with certain co-morbidities. Health care providers will need to evaluate patients carefully should they be eligible for COVID-19 oral antiviral treatments. Alternative therapies should be considered as patients may be precluded from being treated with ritonavir-containing therapies owing to pDDIs.Copyright © 2023

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