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1.
J Med Virol ; 94(4): 1513-1522, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718397

ABSTRACT

OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Indoles/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Sulfides/therapeutic use , COVID-19/mortality , Drug Combinations , Humans , Indoles/adverse effects , Lopinavir/adverse effects , Ritonavir/adverse effects , SARS-CoV-2/drug effects , Sulfides/adverse effects , Treatment Outcome
2.
J Med Virol ; 94(4): 1745-1747, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718409

ABSTRACT

Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID-19). However, we present the case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long-term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID-19 when MP is considered in COVID-19.


Subject(s)
Anti-Inflammatory Agents/adverse effects , Bradycardia/chemically induced , COVID-19/drug therapy , Methylprednisolone/adverse effects , Antiviral Agents/adverse effects , COVID-19/diagnosis , Child , Drug Therapy, Combination/adverse effects , Humans , Indoles/adverse effects , Male , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Sulfides/adverse effects
3.
Medicine (Baltimore) ; 100(28): e26538, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1494086

ABSTRACT

ABSTRACT: Corrected QT (QTc) interval prolongation has been associated with poor patient prognosis. In this study, we assessed the effects of different drugs and cardiac injury on QTc interval prolongation in patients with coronavirus disease 2019 (COVID-19).The study cohort consisted of 395 confirmed COVID-19 cases from the Wuhan Union Hospital West Campus. All hospitalized patients were treated with chloroquine/hydroxychloroquine (CQ/HCQ), lopinavir/ritonavir (LPV/r), quinolones, interferon, Arbidol, or Qingfei Paidu decoction (QPD) and received at least 1 electrocardiogram after drug administration.Fifty one (12.9%) patients exhibited QTc prolongation (QTc ≥ 470 ms). QTc interval prolongation was associated with COVID-19 severity and mortality (both P < .001). Administration of CQ/HCQ (odds ratio [OR], 2.759; 95% confidence interval [CI], 1.318-5.775; P = .007), LPV/r (OR, 2.342; 95% CI, 1.152-4.760; P = .019), and quinolones (OR, 2.268; 95% CI, 1.171-4.392; P = .015) increased the risk of QTc prolongation. In contrast, the administration of Arbidol, interferon, or QPD did not increase the risk of QTc prolongation. Notably, patients treated with QPD had a shorter QTc duration than those without QPD treatment (412.10 [384.39-433.77] vs 420.86 [388.19-459.58]; P = .042). The QTc interval was positively correlated with the levels of cardiac biomarkers (creatine kinase-MB fraction [rho = 0.14, P = .016], high-sensitivity troponin I [rho = .22, P < .001], and B-type natriuretic peptide [rho = 0.27, P < .001]).In conclusion, QTc prolongation was associated with COVID-19 severity and mortality. The risk of QTc prolongation was higher in patients receiving CQ/HCQ, LPV/r, and quinolones. QPD had less significant effects on QTc prolongation than other antiviral agents.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , COVID-19/mortality , Long QT Syndrome/mortality , SARS-CoV-2 , Aged , COVID-19/virology , Chloroquine/adverse effects , Drug Therapy, Combination , Drugs, Chinese Herbal/adverse effects , Electrocardiography , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/adverse effects , Indoles/adverse effects , Interferons/adverse effects , Long QT Syndrome/chemically induced , Lopinavir/adverse effects , Male , Middle Aged , Odds Ratio , Quinolones/adverse effects , Retrospective Studies , Ritonavir/adverse effects , Severity of Illness Index
4.
Nat Commun ; 12(1): 6055, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475294

ABSTRACT

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/administration & dosage , Indoles/administration & dosage , Leucine/administration & dosage , Pyrrolidinones/administration & dosage , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Animals , COVID-19/virology , Chlorocebus aethiops , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/enzymology , Coronavirus Protease Inhibitors/adverse effects , Coronavirus Protease Inhibitors/pharmacokinetics , Disease Models, Animal , Drug Design , Drug Synergism , Drug Therapy, Combination , HeLa Cells , Humans , Indoles/adverse effects , Indoles/pharmacokinetics , Infusions, Intravenous , Leucine/adverse effects , Leucine/pharmacokinetics , Mice , Pyrrolidinones/adverse effects , Pyrrolidinones/pharmacokinetics , SARS Virus/drug effects , SARS Virus/enzymology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Vero Cells
5.
N Engl J Med ; 385(9): 815-825, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1373470

ABSTRACT

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear. METHODS: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and Phe508del-gating or Phe508del-residual function genotypes. After a 4-week run-in period with ivacaftor or tezacaftor-ivacaftor, patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or active control for 8 weeks. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 8 in the elexacaftor-tezacaftor-ivacaftor group. RESULTS: After the run-in period, 132 patients received elexacaftor-tezacaftor-ivacaftor and 126 received active control. Elexacaftor-tezacaftor-ivacaftor resulted in a percentage of predicted FEV1 that was higher by 3.7 percentage points (95% confidence interval [CI], 2.8 to 4.6) relative to baseline and higher by 3.5 percentage points (95% CI, 2.2 to 4.7) relative to active control and a sweat chloride concentration that was lower by 22.3 mmol per liter (95% CI, 20.2 to 24.5) relative to baseline and lower by 23.1 mmol per liter (95% CI, 20.1 to 26.1) relative to active control (P<0.001 for all comparisons). The change from baseline in the Cystic Fibrosis Questionnaire-Revised respiratory domain score (range, 0 to 100, with higher scores indicating better quality of life) with elexacaftor-tezacaftor-ivacaftor was 10.3 points (95% CI, 8.0 to 12.7) and with active control was 1.6 points (95% CI, -0.8 to 4.1). The incidence of adverse events was similar in the two groups; adverse events led to treatment discontinuation in one patient (elevated aminotransferase level) in the elexacaftor-tezacaftor-ivacaftor group and in two patients (anxiety or depression and pulmonary exacerbation) in the active control group. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor was efficacious and safe in patients with Phe508del-gating or Phe508del-residual function genotypes and conferred additional benefit relative to previous CFTR modulators. (Funded by Vertex Pharmaceuticals; VX18-445-104 ClinicalTrials.gov number, NCT04058353.).


Subject(s)
Aminophenols/therapeutic use , Benzodioxoles/therapeutic use , Chloride Channel Agonists/therapeutic use , Cystic Fibrosis/drug therapy , Indoles/therapeutic use , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Quinolines/therapeutic use , Adolescent , Adult , Aminophenols/adverse effects , Benzodioxoles/adverse effects , Child , Chloride Channel Agonists/adverse effects , Chlorides/analysis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Double-Blind Method , Drug Combinations , Female , Genotype , Humans , Indoles/adverse effects , Male , Pyrazoles/adverse effects , Pyridines/adverse effects , Quinolines/adverse effects , Sweat/chemistry
6.
J Glob Health ; 11: 05017, 2021.
Article in English | MEDLINE | ID: covidwho-1335378

ABSTRACT

BACKGROUND: The antiviral therapy has been considered as an ordinary intervention for COVID-19 patients. However, the effectiveness of antiviral therapy is uncertain. This study was designed to determine the association between the antiviral therapy and in-hospital mortality among severe COVID-19 patients. METHODS: This study enrolled severe COVID-19 patients admitted to four designated hospitals in Wuhan, China. The use of antiviral treatments, demographics, laboratory variables, co-morbidities, complications, and other treatments were compared between survival and fatal cases. The association between antiviral agents and in-hospital mortality were analyzed. RESULTS: In total, 109 severe COVID-19 patients (mean age 65.43) were enrolled for analysis, among which, 61 (56.0%) patients were discharged alive, and 48 (44.0%) died during hospitalization. We found no association between lopinavir/ritonavir (LPV/r) treatment and the in-hospital mortality (odds ratio (OR) = 0.195, 95% confidence interval (CI) = 0.023-1.679). Besides, ribavirin (OR = 0.738, 95% CI = 0.344-1.582), oseltamivir (OR = 0.765, 95% CI = 0.349-1.636), and interferon-alpha (IFN-α) (OR = 0.371, 95% CI = 0.112-1.236) were not associated with the in-hospital mortality. However, arbidol monotherapy (OR = 5.027, 95% CI = 1.795-14.074) or the combination of arbidol and oseltamivir (OR = 5.900, 95% CI = 1.190-29.247) was associated with an increased in-hospital mortality. In addition, the multiple logistic regression identified a significant association between the use of arbidol and the in-hospital mortality (adjusted OR = 4.195, 95% CI = 1.221-14.408). CONCLUSIONS: Our findings indicated that LPV/r, IFN-α, ribavirin, or oseltamivir have no beneficial effects on the prognosis of severe COVID-19 patients, whereas the use of arbidol is associated with increased in-hospital mortality.


Subject(s)
COVID-19 , Hospital Mortality , Indoles , Aged , COVID-19/drug therapy , COVID-19/mortality , China/epidemiology , Hospital Mortality/trends , Humans , Indoles/adverse effects , Retrospective Studies , Severity of Illness Index
7.
Int J Infect Dis ; 108: 454-460, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1305241

ABSTRACT

OBJECTIVES: One of the most significant features of poor prognosis in COVID-19 is pulmonary fibrosis. Nintedanib is a new antifibrotic agent that interferes with processes of pulmonary fibrosis. This study aimed to investigate the efficacy and safety of nintedanib in COVID-19. METHODS: This was an interventional study in which adult patients with COVID-19 requiring mechanical ventilation were consecutively enrolled. The primary endpoint was 28-day mortality after the initiation of mechanical ventilation. The secondary endpoints were length of mechanical ventilation, volume of lung injury, and the incidence of gastrointestinal adverse events and acute liver failure. RESULTS: Thirty patients with COVID-19 underwent nintedanib therapy. We included 30 patients not receiving nintedanib as the historical control group. There were no significant differences in 28-day mortality between the groups (23.3% vs 20%, P = 0.834). Lengths of mechanical ventilation were significantly shorter in the nintedanib group (P = 0.046). Computed tomography volumetry showed that the percentages of high-attenuation areas were significantly lower in the nintedanib group at liberation from mechanical ventilation (38.7% vs 25.7%, P = 0.027). There were no significant differences in the adverse events. CONCLUSIONS: The administration of nintedanib may offer potential benefits for minimizing lung injury in COVID-19.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Adult , Humans , Indoles/adverse effects , Respiration, Artificial , SARS-CoV-2
8.
Sci Rep ; 11(1): 13349, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281740

ABSTRACT

Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Here, we evaluated the occurrence of pulmonary adverse drug events (ADEs) in patients with hypertension receiving ACEIs/ARBs to determine if disparities exist between individual drugs within the respective classes using data from the FDA Spontaneous Reporting Systems. For this purpose, we proposed the proportional reporting ratio to provide a statistical summary for the commonality of an ADE for a specific drug as compared to the entire database for drugs in the same or other classes. In addition, a statistical procedure, multiple logistic regression analysis, was employed to correct hidden confounders when causative covariates are underreported or untrusted to correct analyses of drug-ADE combinations. To date, analyses have been focused on drug classes rather than individual drugs which may have different ADE profiles depending on the underlying diseases present. A retrospective analysis of thirteen pulmonary ADEs showed significant differences associated with quinapril and trandolapril, compared to other ACEIs and ARBs. Specifically, quinapril and trandolapril were found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs as well as ARBs (P < 0.0001) for group comparison (i.e., ACEIs vs. ARBs vs. quinapril vs. trandolapril) and (P ≤ 0.0007) for pairwise comparison (i.e., ACEIs vs. quinapril, ACEIs vs. trandolapril, ARBs vs. quinapril, or ARBs vs. trandolapril). This study suggests that specific members of the ACEI antihypertensive class (quinapril and trandolapril) have a significantly higher cluster of pulmonary ADEs.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19 , Hypertension , Indoles/adverse effects , Quinapril/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , Comorbidity , Hospital Mortality , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Retrospective Studies
9.
PLoS One ; 16(6): e0252516, 2021.
Article in English | MEDLINE | ID: covidwho-1256041

ABSTRACT

Gambling Disorder (GD) has recently been reclassified from an impulse-control disorder to a behavioural addiction and, as in other addictive disorders, the dopaminergic reward system is involved. According to neuroimaging studies, alterations within the striatal dopaminergic signalling can occur in GD. However, the findings to date are controversial and there has been no agreement yet on how the reward system is affected on a molecular basis. Within the last 20 years, there has been growing evidence for a higher risk to develop GD in response to certain dopaminergic medication. Especially the dopamine agonists pramipexole and ropinirole, and the dopamine modulator aripiprazole seem to increase the likelihood for GD. The goal of this study was to examine the association between a prescription for either of the three pharmaceuticals and a GD diagnosis in a large cross-sectional study of the Swedish population. Compared to patients with any other dopaminergic drug prescription (38.7% with GD), the diagnosis was more common in patients with a dopamine agonist prescription (69.8% with GD), resulting in an odds ratio of 3.2. A similar association was found between aripiprazole prescriptions and GD diagnoses, which were analysed within the subgroup of all patients with schizophrenia or a schizotypal, delusional, or another non-mood psychotic disorder. An aripiprazole prescription increased the likelihood of GD (88.8%) in comparison to patients without an aripiprazole prescription (71.2%) with an odds ratio of 3.4. This study contributes to the increasingly reliable evidence for an association between several dopaminergic drugs and a higher risk for developing GD. Therefore, one future research goal should be a better understanding of the neurobiology in GD to be able to design more selective dopaminergic medication with less severe side effects. Additionally, this knowledge could enable the development of pharmacotherapy in GD and other addictive disorders.


Subject(s)
Aripiprazole/adverse effects , Behavior, Addictive/chemically induced , Dopamine Agonists/adverse effects , Gambling/chemically induced , Indoles/adverse effects , Pramipexole/adverse effects , Registries , Adult , Aged , Aged, 80 and over , Behavior, Addictive/diagnosis , Behavior, Addictive/epidemiology , Behavior, Addictive/metabolism , Cross-Sectional Studies , Dopamine/metabolism , Female , Gambling/diagnosis , Gambling/epidemiology , Gambling/metabolism , Humans , Male , Middle Aged , Reward , Risk Factors , Sweden/epidemiology , Young Adult
10.
Antivir Ther ; 25(4): 233-239, 2020.
Article in English | MEDLINE | ID: covidwho-1256707

ABSTRACT

Since the outbreak of coronavirus disease (COVID-19) that was discovered in 2019 in Wuhan, China, no standard therapy guideline has been set despite the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its high infectivity. The globally pandemic outbreak suggests that COVID-19 is highly infectious and difficult to control. A dual-combination of ribavirin and interferon-α has been the widely used regimen for the treatment of this disease in China. However, due to the varying results of treatment with these drugs, a novel antiviral combination therapy is urgently needed. This case reports the usage of lopinavir/ritonavir-based combination antiviral regimen for a patient with SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , SARS-CoV-2 , Adult , Drug Therapy, Combination , Humans , Indoles/administration & dosage , Indoles/adverse effects , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Lopinavir/administration & dosage , Lopinavir/adverse effects , Male , Ritonavir/administration & dosage , Ritonavir/adverse effects
11.
Cells ; 10(5)2021 05 14.
Article in English | MEDLINE | ID: covidwho-1234672

ABSTRACT

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Available antifibrotic therapies, namely nintedanib and pirfenidone, might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection but are not economically sustainable by national health systems and have critical adverse effects. It is our opinion that the mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 fibrotic lungs through its anti-inflammatory and antifibrotic factors.


Subject(s)
Biological Factors/pharmacology , COVID-19/complications , Mesenchymal Stem Cells/metabolism , Pulmonary Fibrosis/drug therapy , Biological Factors/metabolism , Biological Factors/therapeutic use , COVID-19/drug therapy , COVID-19/economics , COVID-19/virology , Humans , Indoles/administration & dosage , Indoles/adverse effects , Indoles/economics , Lung/drug effects , Lung/pathology , Lung/virology , Pulmonary Fibrosis/economics , Pulmonary Fibrosis/virology , Pyridones/administration & dosage , Pyridones/adverse effects , Pyridones/economics , SARS-CoV-2/pathogenicity
12.
Ann Palliat Med ; 10(3): 2429-2438, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1029919

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the causative agent of coronavirus disease 2019 (COVID-19). Lung lesions are considered to be the main damage caused by SARSCoV-2 infection. In addition, liver injury has also been reported to occur during the course of the disease in severe cases. However, the effect of antiviral treatment on liver injury in critically ill patients is not yet clear. METHODS: We retrospectively evaluated the effect of antiviral treatment and antiviral drug arbidol on liver injury in COVID-19 critically ill patients. Baseline characteristics were collected from patients who were admitted to intensive care units of Tongji Hospital in Wuhan, China, and confounders were balanced by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. RESULTS: Both the PSM (OR=2.77; 95% CI: 1.03, 7.48; P=0.045) and the IPTW-adjusted (OR=2.33; 95% CI: 1.02, 5.34; P=0.047) results showed that COVID-19 critically ill patients receiving antiviral treatment had a significantly higher risk of liver injury. However, arbidol treatment did not have a significant effect on liver injury (IPTW: OR=2.11; 95% CI: 0.79, 5.67; P=0.14). CONCLUSIONS: Our results show that although arbidol treatment does not seem to be significantly associated with liver injury complications, the overall use of antiviral drugs increases the risk of liver injury for critically ill patients with COVID-19. Antiviral drugs are widely used to treat COVID-19, but we recommend that for critically ill patients, antiviral treatment should be used with caution considering both effectiveness and potential adverse effects.


Subject(s)
Antiviral Agents/adverse effects , COVID-19/drug therapy , Indoles/adverse effects , Liver/drug effects , Antiviral Agents/therapeutic use , Chemical and Drug Induced Liver Injury , China , Critical Illness , Humans , Indoles/therapeutic use , Liver/pathology , Retrospective Studies
13.
Int J Mol Sci ; 22(1)2020 Dec 30.
Article in English | MEDLINE | ID: covidwho-1006950

ABSTRACT

Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families. The drug also affects other kinases, including Src, Flt-3, LCK, LYN. Nintedanib is used in the treatment of idiopathic pulmonary fibrosis, chronic fibrosing interstitial lung diseases and lung cancer. The mechanism of action suggests that nintedanib should be considered one of the potential agents for inhibiting and revising the fibrosis process related to COVID-19 infections. Due to the known induction of coagulation pathways during COVID-19 infections, possible interaction between nintedanib and anticoagulant seems to be an extremely important issue. In theory, nintedanib could increase the bleeding risk, thrombosis and lead to thrombocytopenia. The data from clinical trials on the concomitant use of nintedanib and antithrombotic agents is very limited as this patient group was within the standard exclusion criteria. Nintedanib is an important therapeutic option, despite its interaction with anticoagulants. If anticoagulant therapy is necessary, the more effective and safer option is the concomitant administration of DOACs and nintedanib, especially when drug-monitored therapy will be used in patients at high risk of bleeding complications.


Subject(s)
Anticoagulants/pharmacology , Hemorrhage/etiology , Indoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Anticoagulants/therapeutic use , Antidotes/pharmacology , Antineoplastic Agents/pharmacology , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/drug therapy , COVID-19/complications , COVID-19/drug therapy , COVID-19/metabolism , Drug Interactions , Hemorrhage/epidemiology , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/adverse effects , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Risk Factors
14.
J Zhejiang Univ Sci B ; 21(12): 948-954, 2020.
Article in English | MEDLINE | ID: covidwho-999886

ABSTRACT

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).


Subject(s)
COVID-19/drug therapy , Indoles/therapeutic use , Protease Inhibitors/therapeutic use , Adult , China , Darunavir , Drug Combinations , Female , Humans , Indoles/adverse effects , Lipid Metabolism , Lopinavir , Male , Middle Aged , Protease Inhibitors/adverse effects , Retrospective Studies , Ritonavir , SARS-CoV-2/drug effects , SARS-CoV-2/genetics
15.
Zhongguo Fei Ai Za Zhi ; 23(10): 858-865, 2020 Oct 20.
Article in English | MEDLINE | ID: covidwho-914583

ABSTRACT

BACKGROUND: Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase (RTK) inhibitor that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of anlotinib-bronchial fistula (BF) during the treatment of lung cancer patients and summarize the possible causes. METHODS: We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and PubMed for medical literature published between 2018 and 2020 using the following search terms: "anlotinib," "lung cancer," and "fistula." RESULTS: Our literature search produced two case reports (three patients) which, in addition to our three patients. We collated the patients' clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced age, male, concurrent infection symptoms, diabetes mellitus (DM), advanced squamous cell and small cell lung cancers, centrally located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophago-tracheobronchial fistula. Six patients all died within 6 months. CONCLUSIONS: Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close observation of high-risk patients.


Subject(s)
Antineoplastic Agents/adverse effects , Bronchial Fistula/etiology , Indoles/adverse effects , Lung Neoplasms/drug therapy , Quinolines/adverse effects , Aged , Antineoplastic Agents/therapeutic use , Bronchial Fistula/diagnostic imaging , China , Humans , Indoles/therapeutic use , Male , Middle Aged , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Quinolines/therapeutic use
16.
J Allergy Clin Immunol ; 146(4): 786-789, 2020 10.
Article in English | MEDLINE | ID: covidwho-664612

Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/prevention & control , Drug Hypersensitivity/etiology , Immunologic Factors/adverse effects , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones/therapeutic use , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Amides/administration & dosage , Amides/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/administration & dosage , Betacoronavirus/drug effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/drug therapy , Drug Hypersensitivity/immunology , Humans , Immunity, Innate/drug effects , Immunologic Factors/administration & dosage , Indoles/administration & dosage , Indoles/adverse effects , Infliximab/administration & dosage , Infliximab/adverse effects , Interleukin 1 Receptor Antagonist Protein/administration & dosage , Interleukin 1 Receptor Antagonist Protein/adverse effects , Nitriles , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pyrazines/administration & dosage , Pyrazines/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyrimidines , SARS-CoV-2 , Severity of Illness Index
17.
Clin Microbiol Infect ; 26(7): 917-921, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-116525

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19. METHODS: A retrospective study was performed in a non-intensive care unit (ICU) ward in Jinyintan Hospital from 2 February 2020 to 20 March 2020. COVID-19 was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of pharyngeal swab specimens. The confirmed patients were divided into the umifenovir group and the control group according to the use of umifenovir. The main outcomes were the rate of negative pharyngeal swab tests for SARS-CoV-2 within 1 week after admission and the time for the virus to turn negative. The negativity time of SARS-CoV-2 was defined as the first day of a negative test if the nucleic acid of SARS-CoV-2 was negative for two consecutive tests. RESULTS: A total of 81 COVID-19 patients were included, with 45 in the umifenovir group and 36 in the control group. Baseline clinical and laboratory characteristics were comparable between the two groups. Thirty-three out of 45 (73%) patients in the umifenovir group tested negative for SARS-CoV-2 within 7 days after admission, the number was 28/36 (78%) in the control group (p 0.19). The median time from onset of symptoms to SARS-CoV-2 turning negative was 18 days (interquartile range (IQR) 12-21) in the umifenovir group and 16 days (IQR 11-21) in the control group (p 0.42). Patients in the umifenovir group had a longer hospital stay than patients in the control group (13 days (IQR 9-17) vs 11 days (IQR 9-14), p 0.04). No deaths or severe adverse reactions were found in both groups. DISCUSSION: Umifenovir might not improve the prognosis or accelerate SARS-CoV-2 clearance in non-ICU patients. A randomized control clinical trial is needed to assess the efficacy of umifenovir.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Indoles/therapeutic use , Pneumonia, Viral/drug therapy , Aged , COVID-19 , Female , Humans , Indoles/adverse effects , Length of Stay , Male , Middle Aged , Pandemics , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Treatment Outcome
18.
J Infect ; 81(1): e21-e23, 2020 07.
Article in English | MEDLINE | ID: covidwho-45736

ABSTRACT

Lopinavir/ritonavir and arbidol have been previously used to treat acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) replication in clinical practice; nevertheless, their effectiveness remains controversial. In this study, we evaluated the antiviral effects and safety of lopinavir/ritonavir and arbidol in patients with the 2019-nCoV disease (COVID-19). Fifty patients with laboratory-confirmed COVID-19 were divided into two groups: including lopinavir/ritonavir group (34 cases) and arbidol group (16 cases). Lopinavir/ritonavir group received 400 mg/100mg of Lopinavir/ritonavir, twice a day for a week, while the arbidol group was given 0.2 g arbidol, three times a day. Data from these patients were retrospectively analyzed. The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. None of the patients developed severe pneumonia or ARDS. There was no difference in fever duration between the two groups (P=0.61). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15(44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01). Moreover, no apparent side effects were found in both groups. In conclusion, our data indicate that arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Indoles/therapeutic use , Lopinavir/therapeutic use , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , Adult , Antiviral Agents/administration & dosage , COVID-19 , Coronavirus Infections/virology , Drug Combinations , Female , Humans , Indoles/administration & dosage , Indoles/adverse effects , Lopinavir/adverse effects , Male , Middle Aged , Pandemics , Pneumonia, Viral/virology , Retrospective Studies , Ritonavir/adverse effects , SARS-CoV-2 , Viral Load
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