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1.
Mikrochim Acta ; 189(3): 125, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1712245

ABSTRACT

A novel electrochemical sensor is reported for the detection of the antiviral drug favipiravir based on the core-shell nanocomposite of flower-like molybdenum disulfide (MoS2) nanospheres and molecularly imprinted polymers (MIPs). The MoS2@MIP core-shell nanocomposite was prepared via the electrodeposition of a MIP layer on the MoS2 modified electrode, using o-phenylenediamine as the monomer and favipiravir as the template. The selective binding of target favipiravir at the MoS2@MIP core-shell nanocomposite produced a redox signal in a concentration dependent manner, which was used for the quantitative analysis. The preparation process of the MoS2@MIP core-shell nanocomposite was optimized. Under the optimal conditions, the sensor exhibited a wide linear response range of 0.01 ~ 100 nM (1.57*10-6 ~ 1.57*10-2 µg mL-1) and a low detection limit of 0.002 nM (3.14*10-7 µg mL-1). Application of the sensor was demonstrated by detecting favipiravir in a minimum amount of 10 µL biological samples (urine and plasma). Satisfied results in the recovery tests indicated a high potential of favipiravir monitoring in infectious COVID-19 samples.


Subject(s)
Amides/analysis , Antiviral Agents/analysis , Disulfides/chemistry , Molecularly Imprinted Polymers/chemistry , Molybdenum/chemistry , Nanocomposites/chemistry , Nanospheres/chemistry , Pyrazines/analysis , Amides/blood , Amides/therapeutic use , Amides/urine , Antiviral Agents/blood , Antiviral Agents/therapeutic use , Antiviral Agents/urine , COVID-19/drug therapy , COVID-19/virology , Electrochemical Techniques/methods , Humans , Limit of Detection , Oxidation-Reduction , Pyrazines/blood , Pyrazines/therapeutic use , Pyrazines/urine , Reproducibility of Results , SARS-CoV-2/isolation & purification
2.
Biomed Pharmacother ; 147: 112700, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1664683

ABSTRACT

Coronavirus disease 2019 (COVID-19) represents an unmet clinical need, due to a high mortality rate, rapid mutation rate in the virus, increased chances of reinfection, lack of effectiveness of repurposed drugs and economic damage. COVID-19 pandemic has created an urgent need for effective molecules. Clinically proven efficacy and safety profiles have made favipiravir (FVP) and remdesivir (RDV) promising therapeutic options for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Even though both are prodrug molecules with an antiviral role based on a similar mechanism of action, differences in pharmacological, pharmacokinetic and pharmacotoxicological mechanisms have been identified. The present study aims to provide a comprehensive comparative assessment of FVP and RDV against SARS-CoV-2 infections, by centralizing medical data provided by significant literature and authorized clinical trials, focusing on the importance of a better understanding of the interactions between drug molecules and infectious agents in order to improve the global management of COVID-19 patients and to reduce the risk of antiviral resistance.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Pyrazines/therapeutic use , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Humans , SARS-CoV-2
4.
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
5.
Rheumatol Int ; 42(1): 101-113, 2022 01.
Article in English | MEDLINE | ID: covidwho-1620250

ABSTRACT

Initial case series of small number of patients at the beginning of the pandemic reported a rather guarded prognosis for Behçet's syndrome (BS) patients infected with SARS-CoV-2. In this prospective study, we describe the incidence, clinical characteristics, disease course, management, and outcome in a large cohort of BS patients with laboratory-confirmed infection of SARS-CoV-2. We defined a cohort of 1047 registered BS patients who were aged between 16 and 60 years and seen routinely before the pandemic at the multidisciplinary outpatient clinic. We followed prospectively this cohort from beginning of April 2020 until the end of April 2021. During 13 months of follow-up, of the 1047 (599 M/448 F) patients, 592 (56.5%) were tested for SARS-CoV-2 PCR at least once and 215 (20.5%; 95% CI 0.18-0.23) were tested positive. We observed 2 peaks which took place in December 2020 and April 2021. Of the 215 PCR positive patients, complete information was available in 214. Of these 214, 14 (6.5%) were asymptomatic for COVID-19. In the remaining, the most common symptoms were anosmia, fatigue, fever, arthralgia, and headache. A total of 40 (18.7%) had lung involvement, 25 (11.7%) were hospitalized, 1 was admitted to the intensive care unit while none died. Favipiravir was the most prescribed drug (74.3%), followed by colchicine (40.2%), and hydroxychloroquine (20.1%) in the treatment of COVID-19. After COVID-19, 5 patients (2.3%) were given supplemental O2 and 31 (14.5%) antiaggregant or anticoagulants. During COVID-19, of the 214 PCR positive patients, 116 (54.2%) decreased the dose of their immunosuppressives or stopped taking completely; 36 (16.8%) experienced a BS flare which was mostly oral ulcers (10.3%). None of the patients reported a thrombotic event. A total of 93 (43.5%) patients reported BS flares after a median 45 days of COVID-19 infection and this was found to be significantly associated with immunosuppressive drug discontinuation. Multiple regression analysis adjusted for age and gender indicated that smoking and using interferon-alpha decreased the likelihood of getting COVID-19. The incidence and severity of COVID-19 did not differ between those who were using colchicine or not. The cumulative incidence of COVID-19 in this prospectively followed cohort of BS patients was almost two folds of that estimated for the general population living in Istanbul, Turkey, however, the clinical outcome of COVID-19 was not severe and there was no mortality. The protective effect of smoking and interferon deserves further investigation. On the other hand, colchicine did not have any positive or negative effect against COVID-19. Significant number of patients flared after COVID-19, however, this was significantly associated with immunosuppressive discontinuation during the infection. Contrary to our previous observations, COVID-19 did not seem to exacerbate thrombotic events during or after the infection.


Subject(s)
Behcet Syndrome/epidemiology , COVID-19/epidemiology , Adolescent , Adult , Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Comorbidity , Female , Humans , Hydroxychloroquine/therapeutic use , Incidence , Male , Middle Aged , Prospective Studies , Pyrazines/therapeutic use , Treatment Outcome , Young Adult
6.
BMC Pulm Med ; 22(1): 1, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1608729

ABSTRACT

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.


Subject(s)
COVID-19/classification , COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Body Temperature , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lymphocyte Count , Male , Middle Aged , Mucin-1/blood , Neutrophils , Predictive Value of Tests , Prognosis , Pyrazines/therapeutic use , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies , SARS-CoV-2 , Steroids/therapeutic use
7.
Turk J Med Sci ; 51(6): 2827-2834, 2021 12 13.
Article in English | MEDLINE | ID: covidwho-1580295

ABSTRACT

Background/aim: Due to the importance of early outpatient treatment to prevent hospitalization and disease progression, we examined the effects of hydroxychloroquine and favipiravir, which were initiated in early period, on the clinical course of COVID-19 outpatients. Materials and methods: Data of confirmed COVID-19 outpatients over a 4-month period were analyzed retrospectively. Public Health Management System (HSYS) was used for the case-based follow-up. Patients on antiviral therapy for at least five days, including hydroxychloroquine and / or favipiravir and patients who were followed-up for 30 days were included in this analysis. Results: We enrolled 1489 patients in this study. Overall, 775 (52%) patients were male and a mean age of patients was 38.9 ± 11.1 years. Of these patients, 537 of them were received favipiravir, 545 of them were received hydroxychloroquine and 407 of them were received both favipiravir and hydroxychloroquine. Symptoms improvement on the 14th day of follow-up was 1.8 times higher in the group of patients receiving hydroxychloroquine compared to patients who received favipiravir (p = 0.003). On the 3rd day of follow- up, PCR negativity rate was higher in patients who received hydroxychloroquine (p = 0.004). Hospitalization rates were similar in patients receiving favipiravir and hydroxychloroquine (p = 0.144). However, in the presence of pneumonia at the time of diagnosis, the hospitalization rate was 6.6 times higher in patients who received favipiravir than those who received hydroxychloroquine. Conclusion: The subgroups of patients treated with hydroxychloroquine and/or favipiravir did not have similar disease severities in our study. Therefore, further studies with homogeneous patient groups to be arranged prospectively are needed.


Subject(s)
Amides/therapeutic use , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Pyrazines/therapeutic use , SARS-CoV-2/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Male , Middle Aged , Outpatients , Retrospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome , Turkey/epidemiology , Young Adult
9.
J Med Virol ; 94(1): 291-297, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544344

ABSTRACT

Due to current advances and growing experience in the management of coronavirus Disease 2019 (COVID-19), the outcome of COVID-19 patients with severe/critical illness would be expected to be better in the second wave compared with the first wave. As our hospitalization criteria changed in the second wave, we aimed to investigate whether a favorable outcome occurred in hospitalized COVID-19 patients with only severe/critical illness. Among 642 laboratory-confirmed hospitalized COVID-19 patients in the first wave and 1121 in the second wave, those who met World Health Organization (WHO) definitions for severe or critical illness on admission or during follow-up were surveyed. Data on demographics, comorbidities, C-reactive protein (CRP) levels on admission, and outcomes were obtained from an electronic hospital database. Univariate analysis was performed to compare the characteristics of patients in the first and second waves. There were 228 (35.5%) patients with severe/critical illness in the first wave and 681 (60.7%) in the second wave. Both groups were similar in terms of age, gender, and comorbidities, other than chronic kidney disease. Median serum CRP levels were significantly higher in patients in the second wave compared with those in the first wave [109 mg/L (interquartile range [IQR]: 65-157) vs. 87 mg/L (IQR: 39-140); p < 0.001]. However, intensive care unit admission and mortality rates were similar among the waves. Even though a lower mortality rate in the second wave has been reported in previous studies, including all hospitalized COVID-19 patients, we found similar demographics and outcomes among hospitalized COVID-19 patients with severe/critical illness in the first and second wave.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Care/statistics & numerical data , Severity of Illness Index , Aged , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Azithromycin/therapeutic use , C-Reactive Protein/analysis , COVID-19/epidemiology , COVID-19/pathology , Comorbidity , Drug Combinations , Enoxaparin/therapeutic use , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Male , Methylprednisolone/therapeutic use , Middle Aged , Pyrazines/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , Turkey/epidemiology
10.
Mol Cancer Res ; 20(3): 446-455, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1518187

ABSTRACT

AXL, a receptor tyrosine kinase from the TAM (TYRO3 AXL and MER) subfamily, and its ligand growth arrest-specific 6 (GAS6) are implicated in pathogenesis of a wide array of cancers, acquisition of resistance to diverse anticancer therapies and cellular entry of viruses. The continuous development of AXL inhibitors for treatment of patients with cancer and COVID-19 underscores the need to better characterize the cellular effects of AXL targeting.In the present study, we compared the cellular phenotypes of CRISPR-Cas9-induced depletion of AXL and its pharmacological inhibition with bemcentinib, LDC1267 and gilteritinib. Specifically, we evaluated GAS6-AXL signaling, cell viability and invasion, the endo-lysosomal system and autophagy in glioblastoma cells. We showed that depletion of AXL but not of TYRO3 inhibited GAS6-induced phosphorylation of downstream signaling effectors, AKT and ERK1/2, indicating that AXL is a primary receptor for GAS6. AXL was also specifically required for GAS6-dependent increase in cell viability but was dispensable for viability of cells grown without exogenous addition of GAS6. Furthermore, we revealed that LDC1267 is the most potent and specific inhibitor of AXL activation among the tested compounds. Finally, we found that, in contrast to AXL depletion and its inhibition with LDC1267, cell treatment with bemcentinib and gilteritinib impaired the endo-lysosomal and autophagy systems in an AXL-independent manner. IMPLICATIONS: Altogether, our findings are of high clinical importance as we discovered that two clinically advanced AXL inhibitors, bemcentinib and gilteritinib, may display AXL-independent cellular effects and toxicity.


Subject(s)
Aniline Compounds/therapeutic use , Benzocycloheptenes/therapeutic use , Lysosomes/drug effects , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins/antagonists & inhibitors , Pyrazines/therapeutic use , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Triazoles/therapeutic use , Aniline Compounds/pharmacology , Autophagy , Benzocycloheptenes/pharmacology , Cell Line, Tumor , Cell Proliferation , Humans , Protein Kinase Inhibitors/pharmacology , Pyrazines/pharmacology , Signal Transduction , Transfection , Triazoles/pharmacology
11.
Semin Oncol ; 48(4-6): 279-282, 2021.
Article in English | MEDLINE | ID: covidwho-1510651

ABSTRACT

BACKGROUND: COVID-19 infection increases mortality in hematological malignancies. In a large meta-analysis, patients aged 60 years and older had a significantly higher risk of death than patients under 60 years of age [1]. Furthermore, a high risk of death and reduced survival in patients receiving B cell depletion therapy with prolonged COVID-19 infection was reported in a recent study [2]. High-grade B-cell lymphomas are classified as morphologically aggressive lymphomas with the presence of a high mitotic index and Ki-67 proliferation rates. They demonstrate aggressive behavior clinically as well as morphologically, and COVID-19 infection is an important factor that increases mortality in these patients. Herein, we present an elderly patient with a diagnosis of high-grade B-cell lymphoma, in whom a complete response was observed after prolonged COVID-19 infection. CASE SUMMARY: An 81-year-old female patient received her first cycle of R-CHOP (rituximab, cyclophosphamide, vincristine, and prednisolone) treatment after being diagnosed with high- grade B-cell lymphoma. After being discharged from the hospital, the patient was referred to the emergency department with complaints of fever and fatigue when she came for the second cycle of chemotherapy. Her COVID-19 PCR test was found positive. She was admitted to the infectious diseases service and favipiravir treatment was started. On the 24th day of hospitalization, it was decided to perform interim FDG-PET/CT (Fluorodeoxyglucose - Positron Emission Tomography/Computed Tomography) scan at a time that her PCR (Polymerase Chain Reaction) test was still positive. A complete metabolic response was detected in her imaging. On the 26th day, the PCR test became negative and the patient was transferred to the oncology service and received the second cycle of R-CHOP treatment. CONCLUSION: Our case emphasizes that antitumor effect could be seen in a patient with SARS-CoV-2 infection and a hematologic malignancy. It also highlights being alert to prolonged COVID-19 infection in patients receiving B-cell depletion therapy.


Subject(s)
COVID-19/complications , Cyclophosphamide/therapeutic use , Frail Elderly , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/drug therapy , Prednisone/therapeutic use , Rituximab/therapeutic use , Vincristine/therapeutic use , Aged, 80 and over , Amides/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Positron Emission Tomography Computed Tomography , Pyrazines/therapeutic use , SARS-CoV-2
13.
Diabetes Metab Syndr ; 15(6): 102328, 2021.
Article in English | MEDLINE | ID: covidwho-1487693

ABSTRACT

BACKGROUND AND AIMS: Cardiometabolic disease may confer increased risk of adverse outcomes in COVID-19 patients by activation of the aldose reductase pathway. We hypothesized that aldose reductase inhibition with AT-001 might reduce viral inflammation and risk of adverse outcomes in diabetic patients with COVID-19. METHODS: We conducted an open-label prospective phase 2 clinical trial to assess safety, tolerability and efficacy of AT-001 in patients hospitalized with COVID-19 infection, history of diabetes mellitus and chronic heart disease. Eligible participants were prospectively enrolled and treated with AT-001 1500 mg BID for up to 14 days. Safety, tolerability, survival and length of hospital stay (LOS) were collected from the electronic medical record and compared with data from two matched control groups (MC1 and MC2) selected from a deidentified registry of COVID-19 patients at the same institution. RESULTS: AT-001 was safe and well tolerated in the 10 participants who received the study drug. In-hospital mortality observed in the AT-001 group was 20% vs. 31% in MC1 and 27% in MC2. Mean LOS observed in the AT-001 group was 5 days vs. 10 days in MC1 and 25 days in MC2. CONCLUSIONS: In hospitalized patients with COVID-19 and co-morbid diabetes mellitus and heart disease, treatment with AT-001 was safe and well tolerated. Exposure to AT-001 was associated with a trend of reduced mortality and shortened LOS. While the observed trend did not reach statistical significance, the present study provides the rationale for investigating potential benefit of AT-001 in COVID 19 affected patients in future studies.


Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Benzothiazoles/therapeutic use , COVID-19/drug therapy , Pyrazines/therapeutic use , Pyridones/therapeutic use , Registries , Aged , Benzothiazoles/pharmacology , COVID-19/complications , COVID-19/mortality , Diabetes Complications/drug therapy , Female , Humans , Hypertension/complications , Inpatients , Male , Middle Aged , New York/epidemiology , Pilot Projects , Prospective Studies , Pyrazines/pharmacology , Pyridones/pharmacology
14.
Acta Otolaryngol ; 141(11): 989-993, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1479845

ABSTRACT

BACKGROUND: The effect of Covid-19 infection on nasal mucociliary clearance (MCC) is unknown. AIMS/OBJECTIVES: The aim of this study is to investigate the relationship between Covid-19 and nasal MCC in terms of smoking, Covid-19 symptoms and treatment. METHODS: Thirty-six patients who were hospitalized in the pandemic ward due to Covid-19 and 36 volunteers (Covid-19 negative test result) who presented to the otolaryngology outpatient clinic with non-nasal symptoms were included in this study. The Saccharin test was performed in both groups to evaluate nasal MCC. RESULTS: The patients and control groups were not significantly different in terms of age and gender. The nasal MCC time was significantly higher in the patient group compared to the control group (19.18 ± 10.84 min and 13.78 ± 8.18 min, p = .003). CONCLUSIONS AND SIGNIFICANCE: In this study, we found that Covid-19 prolonged nasal MCC time regardless of age. We suggest that corticosteroids should be included in the treatment of Covid-19, both with its symptom reduction and its positive effect on MCC duration.


Subject(s)
COVID-19/physiopathology , Mucociliary Clearance/physiology , Nasal Mucosa/physiopathology , Smoking/physiopathology , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Adult , Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Case-Control Studies , Female , Humans , Hydroxychloroquine/adverse effects , Length of Stay , Male , Middle Aged , Mucociliary Clearance/drug effects , Pyrazines/therapeutic use
15.
J Infect Dev Ctries ; 15(9): 1273-1276, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1478140

ABSTRACT

INTRODUCTION: An outbreak of coronavirus disease-19 (COVID-19) has occurred in different parts of the world. Although a large piece of information regarding the epidemiology, clinical features, and management of COVID-19 has been reported in the general population, there is very limited data regarding organ transplant recipients, particularly regarding the management of maintenance immunosuppressive agents during infection. METHODOLOGY: We described a case of kidney transplant recipient from Thailand who had COVID-19 pneumonia and severe acute kidney injury. RESULTS: The patient's serum creatinine peaked at 7.0 mg/dL on day 15 of illness and returned to baseline value of 2.0 mg/dL on day 26 of illness. We have shown how we modified tacrolimus, mycophenolate, and steroids in the patient who had received favipiravir and lopinavir/ritonavir for COVID-19 pneumonia. CONCLUSIONS: In this case, successful modification of this immunosuppressive regimen was accomplished to reduce drug interaction complications, aiming to avoid calcineurin inhibitor nephrotoxicity while maintaining appropriate levels of immunosuppression to prevent organ rejection and to promote the patient's recovery from infection.


Subject(s)
Acute Kidney Injury/virology , COVID-19/drug therapy , Immunosuppressive Agents/administration & dosage , Acute Kidney Injury/drug therapy , Adult , Amides/therapeutic use , Drug Combinations , Drug Interactions , Humans , Kidney Transplantation , Lopinavir/therapeutic use , Male , Mycophenolic Acid/administration & dosage , Pyrazines/therapeutic use , Ritonavir/therapeutic use , Steroids/administration & dosage , Tacrolimus/administration & dosage , Thailand , Transplant Recipients
16.
Int J Clin Pract ; 75(12): e14938, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1450550

ABSTRACT

OBJECTIVE: The safety profile of favipiravir in patients with severe renal impairment has not been investigated and available data are insufficient. The study aimed to compare the incidence of favipiravir-associated adverse events amongst patients with varying renal function statuses. METHODS: Records of 921 patients who were hospitalised for COVID-19 and had received at least 5 days of favipiravir treatment were retrospectively evaluated and 228 patients were included in the study. Patients' age, sex, comorbidities, estimated glomerular filtration rate (eGFR) and haematological and biochemical values were recorded. The incidence of adverse events was compared with the age, sex, comorbidities and eGFR of the patients. RESULTS: The mean age of the patients was 59.3 ± 15.6 years, and 38.2% of the patients were women. One hundred and thirty-one (57.5%) patients had experienced adverse events. These adverse effects consisted of ALT elevation (35.5%), AST elevation (21.5%), anaemia (16.2%), hyperuricaemia (10.5%), hepatocellular injury (9.2%), neutropenia (3.5%) and thrombocytopenia (2.6%). The incidence of adverse events was not significantly different when patients had eGFR >60 mL/min/1.73 m2 or eGFR 30-60 mL/min/1.73 m2 (P > .05), but significantly increased when the eGFR dropped to <30 (P < .05). The differences seen with hyperuricaemia and anaemia were significant (P < .05). CONCLUSION: Even though favipiravir appeared to be well tolerated in the individuals with renal failure in this study, its use in this population remains a challenge that requires more research and analysis.


Subject(s)
Amides/therapeutic use , COVID-19 , Pyrazines/therapeutic use , Renal Insufficiency , Adult , Aged , Amides/adverse effects , COVID-19/drug therapy , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Pyrazines/adverse effects , Retrospective Studies
17.
Am J Emerg Med ; 38(7): 1488-1493, 2020 07.
Article in English | MEDLINE | ID: covidwho-1450042

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Drug Therapy, Combination , Emergency Service, Hospital , Humans , Hydroxychloroquine/therapeutic use , Interleukin-6/antagonists & inhibitors , Pandemics , Pyrazines/therapeutic use , Randomized Controlled Trials as Topic , SARS-CoV-2
18.
Jpn J Infect Dis ; 74(5): 416-420, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1436358

ABSTRACT

We retrospectively studied nasopharyngeal severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load in coronavirus disease 2019 (COVID-19) patients who were hospitalized between January 13 and April 1, 2020. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was conducted using primers and probes targeting the ORF1ab and N genes. All patients were classified in the following groups: Group 1: received favipiravir + chloroquine or hydroxychloroquine + lopinavir/ritonavir or darunavir/ritonavir for 5-10 days, Group 2: received chloroquine or hydroxychloroquine + lopinavir/ritonavir or darunavir/ritonavir for 5-10 days, and Group 3: no antiviral medication. Among the 115 patients, 38 (33%), 54 (47%), and 23 (20%) were in Groups 1, 2, and 3, respectively. The median (IQR) baseline viral loads on day 0 of Groups 1, 2, and 3 were 7.2 (6.0-8.1), 6.9 (5.8-7.8), and 6.9 (5.8-7.6) log10 copies/mL, respectively. The reductions of mean viral loads on day 3 from baseline were 2.41, 1.38, and 2.19 log10 copies/mL in the corresponding groups (P < 0.05). There were no differences in the reduction of mean viral loads from baseline among the three groups on days 5 and 10 (P > 0.05). Multiple logistic regression analysis showed that receiving favipiravir was associated with nasopharyngeal viral load reduction at three days (P = 0.001). Significant nasopharyngeal SARS-CoV-2 viral load reduction was achieved in COVID-19 patients who received a favipiravir-containing regimen.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Pyrazines/therapeutic use , SARS-CoV-2/drug effects , Viral Load/drug effects , Adult , COVID-19/diagnosis , COVID-19/virology , Drug Therapy, Combination , Female , Hospitalization , Humans , Male , Middle Aged , Nasopharynx , Retrospective Studies , SARS-CoV-2/isolation & purification , Treatment Outcome
19.
EBioMedicine ; 72: 103595, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1433162

ABSTRACT

BACKGROUND: Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data have been recently reported in COVID-19 patients. METHODS: We here report on the combined antiviral effect of both drugs in a SARS-CoV-2 Syrian hamster infection model. The infected hamsters were treated twice daily with the vehicle (the control group) or a suboptimal dose of each compound or a combination of both compounds. FINDINGS: When animals were treated with a combination of suboptimal doses of Molnupiravir and Favipiravir at the time of infection, a marked combined potency at endpoint is observed. Infectious virus titers in the lungs of animals treated with the combination are reduced by ∼5 log10 and infectious virus are no longer detected in the lungs of >60% of treated animals. When start of treatment was delayed with one day a reduction of titers in the lungs of 2.4 log10 was achieved. Moreover, treatment of infected animals nearly completely prevented transmission to co-housed untreated sentinels. Both drugs result in an increased mutation frequency of the remaining viral RNA recovered from the lungs of treated animals. In the combo-treated hamsters, an increased frequency of C-to-T mutations in the viral RNA is observed as compared to the single treatment groups which may explain the pronounced antiviral potency of the combination. INTERPRETATION: Our findings may lay the basis for the design of clinical studies to test the efficacy of the combination of Molnupiravir/Favipiravir in the treatment of COVID-19. FUNDING: stated in the acknowledgment.


Subject(s)
Amides/therapeutic use , COVID-19/drug therapy , Cytidine/analogs & derivatives , Hydroxylamines/therapeutic use , Lung/virology , Pyrazines/therapeutic use , Amides/pharmacology , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/transmission , Cytidine/pharmacology , Cytidine/therapeutic use , Disease Models, Animal , Drug Therapy, Combination , Female , Hydroxylamines/pharmacology , Mesocricetus , Pyrazines/pharmacology , RNA, Viral , Treatment Outcome , Viral Load
20.
Int Immunopharmacol ; 99: 108043, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1370550

ABSTRACT

BACKGROUND: Regarding the COVID-19 pandemic, potential therapeutic agents are being evaluated almost every day. Ciclosporin, a calcineurin inhibitor, is characterized by beneficial antiviral and immunomodulatory effects. The present study aimed to evaluate the efficacy of ciclosporin in managing COVID-19. METHODS: This study was a prospective non-controlled clinical trial carried out on 20 patients. Confirmed COVID-19 patients received two doses of ciclosporin (10 mg/kg and 5 mg/kg injections) 24 h apart. Mortality rate and the lengths of intensive care unit (ICU) and hospital stays were assessed for all 20 patients. RESULTS: The mortality rate and the need for mechanical ventilation were calculated as 50%. The percentage of ICU admission was 70%. The lengths of ICU and hospital stays were 8.13 ± 6.81 and 14.25 ± 8.55 days, respectively. The levels of ferritin and white blood cells were significantly higher after injecting the second dose of ciclosporin. Seven patients (35%) had radiologically improved lungs after ciclosporin therapy. CONCLUSION: It seems that the protocol of two doses of ciclosporin in combination with favipiravir does not have favorable effects among COVID-19 patients that do not respond to dexamethasone. Controlled trials are needed to confirm the results.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cyclosporine/therapeutic use , Pyrazines/therapeutic use , Adult , Aged , Aged, 80 and over , Dexamethasone/therapeutic use , Drug Monitoring , Drug Therapy, Combination , Female , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Prospective Studies , Respiration, Artificial , SARS-CoV-2 , Treatment Outcome , Young Adult
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