Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
J Med Virol ; 93(12): 6557-6565, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544300

ABSTRACT

The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID-19 patients during a 10-day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C-reactive protein (CRP) (-14.29, (95% CI: -26.87, -1.71), p = 0.03) and potassium (-0.53, (95% CI: -1.03, -0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger-scale studies are recommended.


Subject(s)
Antiviral Agents/therapeutic use , Atazanavir Sulfate/therapeutic use , COVID-19/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Oxazines/therapeutic use , Piperazines/therapeutic use , Pyridones/therapeutic use , Ritonavir/therapeutic use , Antiviral Agents/administration & dosage , Atazanavir Sulfate/administration & dosage , COVID-19/pathology , Drug Combinations , Drug Therapy, Combination , Female , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Oxazines/administration & dosage , Piperazines/administration & dosage , Pyridones/administration & dosage , Ritonavir/administration & dosage , Treatment Outcome
2.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1525396

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
3.
JAMA ; 326(17): 1703-1712, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1460106

ABSTRACT

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Factor Xa Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thrombosis/prevention & control , Adult , Aspirin/adverse effects , COVID-19/complications , Dose-Response Relationship, Drug , Double-Blind Method , Early Termination of Clinical Trials , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects
4.
J Med Virol ; 93(12): 6557-6565, 2021 12.
Article in English | MEDLINE | ID: covidwho-1306657

ABSTRACT

The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID-19 patients during a 10-day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C-reactive protein (CRP) (-14.29, (95% CI: -26.87, -1.71), p = 0.03) and potassium (-0.53, (95% CI: -1.03, -0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger-scale studies are recommended.


Subject(s)
Antiviral Agents/therapeutic use , Atazanavir Sulfate/therapeutic use , COVID-19/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Oxazines/therapeutic use , Piperazines/therapeutic use , Pyridones/therapeutic use , Ritonavir/therapeutic use , Antiviral Agents/administration & dosage , Atazanavir Sulfate/administration & dosage , COVID-19/pathology , Drug Combinations , Drug Therapy, Combination , Female , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Male , Middle Aged , Oxazines/administration & dosage , Piperazines/administration & dosage , Pyridones/administration & dosage , Ritonavir/administration & dosage , Treatment Outcome
5.
Muscle Nerve ; 64(2): 215-219, 2021 08.
Article in English | MEDLINE | ID: covidwho-1245512

ABSTRACT

INTRODUCTION/AIMS: Cortical hyperexcitability is a feature of amyotrophic lateral sclerosis (ALS) and cortical excitability can be measured using transcranial magnetic stimulation (TMS). Resting motor threshold (MT) is a measure of cortical excitability, largely driven by glutamate. Perampanel, a glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker, is predicted to increase the cortical excitability threshold. This study aimed to evaluate TMS to functionally assess target engagement in a study of perampanel in ALS. METHOD: We studied the MT of ALS patients randomized to a single dose of perampanel or placebo 5:1 hourly for 4 h. Twelve patients participated at 4 mg and 7 returned for dosing and retesting at 8 mg. The study was terminated in April 2020 due to coronavirus disease 2019-related restrictions, after 7 out of 12 planned patients had received the 8 mg dose. Serum concentrations were also measured. RESULTS: Ten patients received the 4 mg dose (2 received placebo) and 5 received the 8 mg dose (2 received placebo). Motor Threshold increased at 2 h after dosing in the combined treatment group +7% of maximal stimulator output (P < .01). Change could be detected in the larger 4 mg group (P = .02), but not in the smaller 8 mg dose group (P = .1). No side effects were reported after single dose exposure. DISCUSSION: This study shows that perampanel effects the physiology of upper motor neurons. Studies aiming at gauging the effect of perampanel on ALS disease progression are already ongoing. Motor threshold may serve as a marker of biological target engagement.


Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Cortical Excitability/drug effects , Motor Neurons/drug effects , Pyridones/administration & dosage , Receptors, AMPA/antagonists & inhibitors , Aged , Amyotrophic Lateral Sclerosis/blood , Amyotrophic Lateral Sclerosis/diagnosis , Cortical Excitability/physiology , Double-Blind Method , Evoked Potentials, Motor/drug effects , Evoked Potentials, Motor/physiology , Female , Humans , Male , Middle Aged , Motor Neurons/physiology , Nitriles , Pilot Projects , Pyridones/blood , Receptors, AMPA/physiology , Transcranial Magnetic Stimulation/methods
6.
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
7.
Neurologist ; 26(3): 108-111, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1214713

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulable state, increasing the risk for ischemic stroke. In select cases, patients are already on anticoagulation therapy. Such examples highlight the severity of COVID-19's hyperthrombotic state, and raise questions regarding optimal stroke prevention in these patients. CASE REPORT: An 84-year-ool male with past medical history of chronic obstructive pulmonary disease, hypertension, and paroxysmal atrial fibrillation was admitted for respiratory failure secondary to COVID-19 pneumonia. He was continued on his home apixaban 5 mg twice daily. On day 2 of admission, he developed a new aphasia, and right-sided facial droop. Computed tomography (CT) head was unrevealing. CT angiography did not show large vessel occlusion. CT perfusion demonstrated a left middle cerebral artery ischemic penumbra, without core. He was not eligible for thrombolysis or thrombectomy interventions. Later CT head confirmed L middle cerebral artery infarct. The patient's D-dimer was 1,184 ng/mL on day 1 of admission, and increased to 111,574 by day 4. His hypoxia worsened, requiring intubation and transfer to the ICU. He experienced further clinical decline and eventual demise. CONCLUSION: Ischemic stroke in anticoagulated patients with COVID-19 has been previously reported. Such cases emphasize the severity of the coronavirus virus associated hypercoagulable state. A majority of reported cases have occurred in patients continuing their ambulatory therapy. Overall, such cases are likely underreported. There are current trials comparing therapeutic versus prophylactic dose anticoagulation in patients with COVID-19. There are no studies specifically addressing anticoagulation agent failure in these patients. Further research is required this area to determine the optimal therapy for patients with COVID-19.


Subject(s)
COVID-19/complications , Factor Xa Inhibitors/administration & dosage , Ischemic Stroke/etiology , Aged, 80 and over , Atrial Fibrillation/drug therapy , Fatal Outcome , Humans , Hypertension/drug therapy , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Pyrazoles/administration & dosage , Pyridones/administration & dosage
8.
BMJ Case Rep ; 13(12)2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-999235

ABSTRACT

Intra-abdominal thromboses are a poorly characterised thrombotic complication of COVID-19 and are illustrated in this case. A 42-year-old man with chronic hepatitis B (undetectable viral load, FibroScan 7.4 kPa) developed fever and cough in March 2020. 14 days later, he developed right upper quadrant pain. After being discharged with reassurance, he re-presented with worsening pain on symptom day 25. Subsequent abdominal ultrasound suggested portal vein thrombosis. CT of the abdomen confirmed portal and mid-superior mesenteric vein thromboses. Concurrent CT of the chest suggested COVID-19 infection. While reverse transcription PCR was negative, subsequent antibody serology was positive. Thrombophilia screen excluded inherited and acquired thrombophilia. Having been commenced on apixaban 5 mg two times per day, he is currently asymptomatic. This is the first case of COVID-19-related portomesenteric thrombosis described in the UK. A recent meta-analysis suggests 9.2% of COVID-19 cases develop abdominal pain. Threshold for performing abdominal imaging must be lower to avoid this reversible complication.


Subject(s)
COVID-19 , Hepatitis B, Chronic/complications , Mesenteric Ischemia , Mesenteric Veins/diagnostic imaging , Portal Vein/diagnostic imaging , Pyrazoles/administration & dosage , Pyridones/administration & dosage , SARS-CoV-2/isolation & purification , Abdominal Pain/diagnosis , Adult , COVID-19/blood , COVID-19/complications , COVID-19/therapy , COVID-19 Serological Testing/methods , Diagnosis, Differential , Factor Xa Inhibitors/administration & dosage , Humans , Male , Mesenteric Ischemia/etiology , Mesenteric Ischemia/physiopathology , Mesenteric Ischemia/therapy , Portography/methods , Tomography, X-Ray Computed/methods , Treatment Outcome , Ultrasonography/methods
9.
BMJ Case Rep ; 13(11)2020 Nov 04.
Article in English | MEDLINE | ID: covidwho-957913

ABSTRACT

A 60-year-old man recently admitted for bipedal oedema, endocarditis and a persistently positive COVID-19 swab with a history of anticoagulation on rivaroxaban for atrial fibrillation, transitional cell carcinoma, cerebral amyloid angiopathy, diabetes and hypertension presented with sudden onset diplopia and vertical gaze palsy. Vestibulo-ocular reflex was preserved. Simultaneously, he developed a scotoma and sudden visual loss, and was found to have a right branch retinal artery occlusion. MRI head demonstrated a unilateral midbrain infarct. This case demonstrates a rare unilateral cause of bilateral supranuclear palsy which spares the posterior commisure. The case also raises a question about the contribution of COVID-19 to the procoagulant status of the patient which already includes atrial fibrillation and endocarditis, and presents a complex treatment dilemma regarding anticoagulation.


Subject(s)
Aspirin/administration & dosage , Atrial Fibrillation , Blindness , Brain Stem Infarctions , Coronavirus Infections , Diplopia , Endocarditis, Bacterial , Ophthalmoplegia , Pandemics , Pneumonia, Viral , Pyrazoles/administration & dosage , Pyridones/administration & dosage , Retinal Artery Occlusion , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Betacoronavirus/isolation & purification , Blindness/diagnosis , Blindness/etiology , Brain Stem Infarctions/diagnostic imaging , Brain Stem Infarctions/drug therapy , Brain Stem Infarctions/physiopathology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Diplopia/diagnosis , Diplopia/etiology , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/physiopathology , Factor Xa Inhibitors/administration & dosage , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Ophthalmoplegia/diagnosis , Ophthalmoplegia/etiology , Platelet Aggregation Inhibitors/administration & dosage , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Retinal Artery Occlusion/diagnostic imaging , Retinal Artery Occlusion/drug therapy , Retinal Artery Occlusion/etiology , Retinal Artery Occlusion/physiopathology , SARS-CoV-2 , Tomography, Optical Coherence/methods , Treatment Outcome
10.
BMJ Case Rep ; 13(11)2020 Nov 30.
Article in English | MEDLINE | ID: covidwho-949258

ABSTRACT

We report an unusual complication of COVID-19 infection in a 53-year-old Caucasian man. He presented with shortness of breath, fever and pleuritic chest pain. A CT pulmonary angiogram (CTPA) demonstrated acute bilateral pulmonary embolism and bilateral multifocal parenchymal ground glass change consistent with COVID-19 (SARS-CoV-2) infection. Right adrenal haemorrhage was suspected on the CTPA which was confirmed on triple-phase abdominal CT imaging. A short Synacthen test revealed normal adrenal function. He was treated initially with an intravenous heparin infusion, which was changed to apixaban with a planned outpatient review in 3 months' time. He made an uncomplicated recovery and was discharged. Follow-up imaging nearly 5 months later showed near complete resolution of the right adrenal haemorrhage with no CT evidence of an underlying adrenal lesion.


Subject(s)
Adrenal Gland Diseases , Adrenal Glands/diagnostic imaging , COVID-19 , Computed Tomography Angiography/methods , Hemorrhage , Heparin/administration & dosage , Pulmonary Embolism , Pyrazoles/administration & dosage , Pyridones/administration & dosage , Adrenal Cortex Function Tests/methods , Adrenal Gland Diseases/diagnosis , Adrenal Gland Diseases/etiology , Adrenal Gland Neoplasms/diagnosis , Antithrombins/administration & dosage , COVID-19/complications , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/therapy , Clinical Deterioration , Diagnosis, Differential , Hemorrhage/diagnosis , Hemorrhage/etiology , Humans , Male , Middle Aged , Pulmonary Embolism/diagnosis , Pulmonary Embolism/etiology , Pulmonary Embolism/physiopathology , Pulmonary Embolism/therapy , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Treatment Outcome
11.
Eur J Pharm Sci ; 157: 105631, 2021 Feb 01.
Article in English | MEDLINE | ID: covidwho-893750

ABSTRACT

BACKGROUND: Effective antiviral drugs for COVID-19 are still lacking. This study aims to evaluate the clinical outcomes and plasma concentrations of baloxavir acid and favipiravir in COVID-19 patients. METHODS: Favipiravir and baloxavir acid were evaluated for their antiviral activity against SARS-CoV-2 in vitro before the trial initiation. We conducted an exploratory trial with 3 arms involving hospitalized adult patients with COVID-19. Patients were randomized assigned in a 1:1:1 ratio into baloxavir marboxil group, favipiravir group, and control group. The primary outcome was the percentage of subjects with viral negative by Day 14 and the time from randomization to clinical improvement. Virus load reduction, blood drug concentration and clinical presentation were also observed. The trial was registered with Chinese Clinical Trial Registry (ChiCTR 2000029544). RESULTS: Baloxavir acid showed antiviral activity in vitro with the half-maximal effective concentration (EC50) of 5.48 µM comparable to arbidol and lopinavir, but favipiravir didn't demonstrate significant antiviral activity up to 100 µM. Thirty patients were enrolled. The percentage of patients who turned viral negative after 14-day treatment was 70%, 77%, and 100% in the baloxavir marboxil, favipiravir, and control group respectively, with the medians of time from randomization to clinical improvement was 14, 14 and 15 days, respectively. One reason for the lack of virological effect and clinical benefits may be due to insufficient concentrations of these drugs relative to their antiviral activities. One of the limitations of this study is the time from symptom onset to randomization, especially in the baloxavir marboxil and control groups, which is higher than the favipiravir group. CONCLUSIONS: Our findings could not prove a benefit of addition of either baloxavir marboxil or favipiravir under the trial dosages to the existing standard treatment.


Subject(s)
Amides , COVID-19 , Dibenzothiepins , Morpholines , Pyrazines , Pyridones , Triazines , Amides/administration & dosage , Amides/blood , Amides/pharmacokinetics , Antiviral Agents/administration & dosage , Antiviral Agents/blood , Antiviral Agents/pharmacokinetics , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/physiopathology , Dibenzothiepins/administration & dosage , Dibenzothiepins/blood , Dibenzothiepins/pharmacokinetics , Drug Monitoring/methods , Female , Humans , Inhibitory Concentration 50 , Male , Middle Aged , Morpholines/administration & dosage , Morpholines/blood , Morpholines/pharmacokinetics , Pyrazines/administration & dosage , Pyrazines/blood , Pyrazines/pharmacokinetics , Pyridones/administration & dosage , Pyridones/blood , Pyridones/pharmacokinetics , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Symptom Assessment , Treatment Outcome , Triazines/administration & dosage , Triazines/blood , Triazines/pharmacokinetics , Viral Load/drug effects
12.
J Stroke Cerebrovasc Dis ; 29(8): 104982, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-343281

ABSTRACT

We report a case of ophthalmic artery occlusion (OAO) in a young patient with COVID-19 infection that was on therapeutic anticoagulation with apixaban for deep venous thrombosis (DVT). A 48-year-old man with obesity was hospitalized with a severe form of COVID-19 infection, complicated with acute respiratory failure, septic shock, dilated cardiomyopathy and fungemia. Despite treatment with prophylactic enoxaparin (initial D-Dimer 1.14 µg/ml FEU (normal < 0.05 µg/ml FEU), D-Dimer increased to above 20 µg/ml FEU and patient continued to spike high fevers. This prompted further investigations and upper and lower extremities DVTs were confirmed and managed with enoxaparin 1 mg/kg twice daily. D-dimer level decreased to 4.98 µg/ml FEU while on therapeutic anticoagulation. Three weeks later pending hospital discharge, the anticoagulation was switched to oral apixaban 10 mg twice daily. Patient developed acute severe right eye visual loss of no light perception and was diagnosed with incomplete OAO. D-Dimer was elevated at 2.13 µg/ml FEU. Stroke etiological work-up found no embolic sources, resolution of the dilated cardiomyopathy and negative antiphospholipid antibodies. Treatment was changed to enoxaparin and no thrombotic events were encountered to date. Ocular vascular complications have not yet been reported in COVID-19. Controversy exists on the best management algorithm for the hypercoagulable state associated to COVID-19 Either direct oral anticoagulants or low-molecular-weight-heparin are considered appropriate at discharge for patients with venous thromboembolism. The optimum regimen for ischemic stroke prevention and the significance of D-Dimer for anticoagulation monitoring in COVID-19 remain unclear.


Subject(s)
Arterial Occlusive Diseases/etiology , Coronavirus Infections/drug therapy , Factor Xa Inhibitors/administration & dosage , Ophthalmic Artery , Pneumonia, Viral/drug therapy , Pyrazoles/administration & dosage , Pyridones/administration & dosage , Venous Thrombosis/drug therapy , Arterial Occlusive Diseases/diagnostic imaging , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Drug Substitution , Enoxaparin/administration & dosage , Factor Xa Inhibitors/adverse effects , Host Microbial Interactions , Humans , Male , Middle Aged , Ophthalmic Artery/diagnostic imaging , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pyrazoles/adverse effects , Pyridones/adverse effects , Risk Factors , SARS-CoV-2 , Treatment Outcome , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/virology
13.
J Thromb Haemost ; 18(6): 1320-1323, 2020 06.
Article in English | MEDLINE | ID: covidwho-116313

ABSTRACT

BACKGROUND: Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. METHODS: All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. RESULTS: Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period. CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.


Subject(s)
Antithrombins/blood , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Dabigatran/blood , Factor Xa Inhibitors/blood , Pneumonia, Viral/drug therapy , Pyrazoles/blood , Pyridines/blood , Pyridones/blood , Thiazoles/blood , Administration, Oral , Aged , Aged, 80 and over , Antithrombins/administration & dosage , Antithrombins/adverse effects , Antiviral Agents/administration & dosage , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Dabigatran/administration & dosage , Dabigatran/adverse effects , Darunavir/adverse effects , Drug Interactions , Drug Monitoring , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Female , Hemorrhage/chemically induced , Humans , Italy , Lopinavir/adverse effects , Male , Pandemics , Patient Safety , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridones/administration & dosage , Pyridones/adverse effects , Risk Assessment , Risk Factors , Ritonavir/adverse effects , SARS-CoV-2 , Severity of Illness Index , Thiazoles/administration & dosage , Thiazoles/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL